Latest news. https://www.lifesci.tohoku.ac.jp/ Graduate School of Life Sciences, Tohoku University 2026-04-09T15:00:00+09:00

https://www.tohoku.ac.jp/en/press/fish_steals_glowing_protein.html 2025-11-11T10:00:00+09:00

Our brains do not react in a fixed, mechanical way like electronic circuits. Even if we see the same scene every day on our commute to work, what we feel—and whether it leaves a lasting impression—depends on our internal state at that moment. For example, your commute may be a blur if you’re too tired to pay attention to your surroundings.   The 24-hour cycle that humans naturally follow is one of the factors that shapes the brain’s internal environment. These internal physiological cycles arise from the interplay between the body’s intrinsic circadian clock and the external light-dark cycle that synchronizes it. Yet how such daily fluctuations influence brain chemistry and affect neuronal excitability and plasticity has remained largely unknown. Now, researchers at Tohoku University have directly observed time-of-day-dependent changes in neural signal responses in the brains of nocturnal rats.   The findings were published in Neuroscience Research on October 31, 2025.   Figure 1.  Nocturnal rats are active at night and accumulate fatigue toward dawn. Using optogenetic stimulation of cortical neurons and simultaneous local field potential (LFP) recordings, the study revealed that neural responses were weaker before sunrise and stronger before sunset, indicating a roughly 24-hour rhythm in cortical activity. © Yuki Donen, Yoko Ikoma, Ko Matsui   Using optogenetics, the team activated neurons in the visual cortexes of rats and recorded the resulting electrical activity. This approach allowed precise quantification of neural responsiveness. They found that identical neural stimuli evoked different responses depending on the time of day. Neural activity was reduced at sunrise and enhanced at sunset. Since rats are nocturnal, sunrise represents the period after a night of activity when they are preparing to sleep.   To explore the underlying mechanism explaining why this was occurring, the researchers looked at adenosine, a neuromodulator that accumulates during wakefulness and makes us feel sleepy. When the researchers blocked the action of adenosine, neural activity at sunrise became disinhibited and enhanced , showing that adenosine helps regulate cortical excitability across the day. "Neural excitability is not constant; it depends on the brain's internal state," says Professor Ko Matsui of Tohoku University. "Our results show that even identical neurons can respond differently depending on the time of day, governed by molecules like adenosine that link metabolism, sleep, and neuronal signaling.   The team also examined whether the brain’s capacity for long-term potentiation (LTP), a cellular basis of learning and memory, changes with time of day. This represents the brain’s potential for metaplasticity (the brain’s ability to adjust how easily its networks change). Remarkably, repetitive optical stimulation induced LTP-like enhancement at sunrise, but not at sunset. This was unexpected, as it suggests that although sleep pressure and fatigue peak at sunrise, the brain’s metaplastic potential is heightened at this time. These findings indicate that the brain’s ability to reorganize itself follows a daily rhythm, with specific periods more favorable for learning and adaptation.   "These results imply that our brains have temporal windows that favor adaptability," explains lead investigator Yuki Donen. "Knowing when the brain is most receptive to changing could help optimize training, rehabilitation, and stimulation-based therapies.   In humans, who are mainly active during daylight hours, the capacity for learning and memory formation may peak during the twilight period approaching sunset. In other words, the best time to study or learn something new may be before bedtime.   The study reveals how daily rhythms fine-tune the balance between excitability and plasticity in the cortex. Because adenosine levels and sleep pressure follow circadian patterns, this mechanism may synchronize brain adaptability with behavioral cycles such as rest and activity. The research provides new insight into how the brain coordinates energy use, neural signaling, and learning capacity across the day.       Figure 2. Recording daily rhythms of cortical neural signals. (A) In Thy1-ChR2 rats, cortical neurons were optogenetically activated, and local field potentials (LFPs) were recorded in the visual cortex. (B) The slope of the third negative LFP phase was larger at sunset than at sunrise, indicating stronger responses in the evening. (C) Averaged signals over three days showed a ~24-hour sinusoidal pattern synchronized with the light-dark cycle. © Yuki Donen, Yoko Ikoma, Ko Matsui   <Publication Details>  Title:    Diurnal modulation of optogenetically evoked neural signals Authors: Yuki Donen, Yoko Ikoma, Ko Matsui Journal: Neuroscience Research DOI:    https://doi.org/10.1016/j.neures.2025.104981     Link Tohoku University   Contact: Ko Matsui, Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University Email: matsui@med.tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/      

https://www.lifesci.tohoku.ac.jp/ 2025-03-24T14:00:00+09:00

Cell survival depends on the energy molecule adenosine triphosphate (ATP) – it’s like the fuel that keeps our brain running. Intracellular ATP levels are thought to remain constant, given its importance. To maintain this stability, the brain strikes a delicate balance between metabolic energy supply and how much energy our brain is using (neuronal activity).   Purposely causing an imbalance in this carefully regulated system and observing the effects can reveal surprising insights. Researchers from Tohoku University challenged the mouse brain with a metabolic load induced by epileptic seizures, and observed fluctuations in blood volume, astrocytic pyruvate, and neuronal ATP. They found that a single epileptic seizure could greatly reduce ATP. This finding may help redefine our understanding of brain energy dynamics, and how it impacts individuals with epilepsy.   The findings were published in the Journal of Neurochemistry on March 20, 2025.   <Figure 1> During an epileptic seizure, pyruvate levels in astrocytes increased, while ATP levels in neurons decreased. The experiments suggest that the transfer of metabolic energy molecule transfer may be temporarily disrupted during an epileptic episode. © Kota Furukawa, Ko Matsui   An optical fiber inserted into the hippocampus of mice allowed the researchers to visualize fluorescent ATP, or pyruvate sensors in neurons or astrocytes, respectively, to measure fluctuations in these metabolites. A train of electrical stimulation in the hippocampus induced a hyperactive response resembling epileptic seizures. In response, ATP levels in neurons decreased, while pyruvate levels in astrocytes increased.      The brain accounts for 2% of body mass but consumes 20% of the body’s total glucose. Although glucose and oxygen are supplied to the brain through blood vessels, neurons don’t directly contact these vessels—astrocytes do. Astrocytes take up glucose, convert it into pyruvate, and then into lactate. The lactate is released and later taken up by neurons, which convert it back into pyruvate to produce ATP. During the induced epileptic seizure, it is possible that this lactate shuttle was temporarily shut down, causing an accumulation of excess pyruvate in astrocytes and a decrease in neuronal ATP.      The same stimulation leads to varying lengths of neuronal hyperactivity (after discharges; ADs). Although a prolonged AD would typically consume more energy, they found that the reduction in neuronal ATP remained the same. Interestingly, the reduction in neuronal ATP levels decreased as epilepsy developed, while the local blood volume increased. This rise in metabolic energy supply may partially compensate for the loss of ATP in neurons.     <Figure 2> Despite the same intensity of hippocampal stimulation, the duration of epileptic neuronal hyperactivity varied in the same animals. However, the reduction in intracellular neuronal ATP remained constant, suggesting that the varying degree of ATP consumption during neuronal hyperactivity has little impact on net ATP levels. © Kota Furukawa, Ko Matsui   These results suggest that the supply of energy molecules from blood vessels and astrocytes may play a much more significant role in determining ATP levels than previously thought.   “We believe this could change how we understand energy management in the brain,” says Professor Ko Matsui of Tohoku University. “The key to understanding the brain’s super energy-saving, information-processing capabilities may lie in studying the neuron-metabolic system.”   Lead investigator Kota Furukawa believes understanding brain energy dynamics could be the key to treating brain diseases. “This may just be a glimpse of how astrocytes and blood vessels affect epilepsy pathology,” Furukawa explains. “An intricate neuron-metabolic system provides stable energy for daily information processing. A glitch in this system could underlie numerous brain diseases - not just epilepsy, but also mental illnesses.”   <Figure 3>  Caption: With repeated hippocampal stimulation, seizures intensify. As seizures intensify, neuronal ATP decreases, and local blood volume increases. © Kota Furukawa, Ko Matsui     <Link> TOHOKU University     <Publication Details>  Title: Dynamics of neuronal and astrocytic energy molecules in epilepsy Authors: Kota Furukawa, Yoko Ikoma, Yusuke Niino, Yuichi Hiraoka, Kohichi Tanaka, Atsushi Miyawaki, Johannes Hirrlinger, Ko Matsui Journal: Journal of Neurochemistry DOI: https://doi.org/10.1111/jnc.70044   <Contact>  Ko Matsui Super-network Brain Physiology, Graduate School of Life Sciences Email: matsui@tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/  

https://www.lifesci.tohoku.ac.jp/ 2025-02-17T15:30:00+09:00

In an effort to monitor biodiversity trends, greater efforts are being made worldwide to assess biodiversity patterns over large scales. To do this, scientists rely on species distribution models (SDMs), which make predictions of species' geographical ranges based on species data and environmental variables. With these models, scientists can make predictions of habitat suitability under different global change scenarios and tailor management and conservation efforts accordingly.   The international Group on Earth Observations Biodiversity Observation Network (GEO BON), which pools resources and researchers from across the globe, has recently conceptualized "essential biodiversity variables" to standardize the collection and coordination of biodiversity data, and many of these variables can be made with SDMs. Most cutting-edge SDM techniques are implemented in R, a popular statistical programming language, and many new tools have surfaced in recent years in the form of R packages. But researchers often get overwhelmed by the plethora of R packages out there, wondering, 'Which one should I use for my research?'   In a new paper, Jamie M. Kass, associate professor and head of the Macroecology Lab at Tohoku University's Graduate School of Life Sciences, argues that SDM workflows benefit highly from use of multiple packages. Kass, who has helped develop several R packages for SDMs - including ENMeval (which fine-tunes machine-learning SDMs) and wallace (a user-friendly application for SDM workflows) - teamed up with experts worldwide to create a guide for using multiple R package tools effectively and in innovative ways.   The team introduced a new R meta-package called sdmverse, which catalogs R packages for SDMs by the functions they offer and provides visualization features to help researchers understand how they relate to each other. They also contributed three real-world case studies in R showing how combining tools can broaden the diversity of analyses possible and help meet more methodological standards for the field.   "New tools help science move forward, but they can also be overwhelming," says Kass. "We wanted to create a roadmap that shows researchers how to navigate these tools and use them together for better biodiversity modeling."   By following their approach, researchers can improve accuracy, tackle a wider range of questions, and contribute to stronger biodiversity assessments worldwide. As environmental challenges grow, using the best available tools--together - will be essential for tracking trends in biodiversity and protecting nature.   These plots, generated with the new sdmverse R package, show functionalities provided by R packages for species distribution modeling and the relationships between them. ©Ecography     Publication Details: Title: Achieving higher standards in species distribution modeling by leveraging the diversity of available software Authors: Jamie M. Kass, Adam B. Smith, Dan L. Warren, Sergio Vignali, Sylvain Schmitt, Matthew E. Aiello-Lammens, Eduardo Arlé, Ana Márcia Barbosa, Olivier Broennimann, Marlon E. Cobos, Maya Guéguen, Antoine Guisan, Cory Merow, Babak Naimi, Michael P. Nobis, Ian Ondo, Luis Osorio-Olvera, Hannah L. Owens, Gonzalo E. Pinilla-Buitrago, Andrea Sánchez-Tapia, Wilfried Thuiller, Roozbeh Valavi, Santiago José Elías Velazco, Alexander Zizka, Damaris Zurell Journal: Ecography DOI: 10.1111/ecog.07346   Press release Tohoku University   Contact: Jamie M Kass, Email: kass(at)tohoku.ac.jp Website: https://macroecolab.github.io/

https://www.lifesci.tohoku.ac.jp/ 2024-11-27T08:30:00+09:00

https://www.tohoku.ac.jp/en/press/new_smart_agriculture_technology_for_monitoring_plants.html 2024-11-19T10:00:00+09:00

When complex multicellular organisms grow and develop, their tissues must undergo remodeling. As new cells begin to proliferate, old cells must be removed to make room and maintain tissue balance and function. One example of this is in the Drosophila (fruit fly) abdominal epithelium during metamorphosis, where larval epidermal cells (LECs) are replaced by histoblasts, which are the precursors of the adult cells. In a recent article published in PLOS Biology, a team of researchers from Tohoku University, led by researchers at Osaka University, describe new molecular details behind how LEC removal is carefully coordinated.   During Drosophila development, LECs slowly begin to undergo apoptosis. In the late phase, the LECs are rapidly eliminated, with full replacement by the histoblasts. Although the importance of this process was well-defined, the specific mechanisms controlling it were unclear. The team became interested in how LEC removal is affected by endocytosis, the process through which substances are ingested or taken up by cells. "Our group recently published a study showing that reduced endocytic activity can stimulate certain molecular events that result in LEC apoptosis,” says Kevin Yuswan (Tohoku University), lead author of the study. “This increased our interest in the epidermal growth factor receptor (EGFR) pathway because previous work indicated that it may be regulated by endocytosis."   Using various molecular and cellular methods, the team found that the accelerated LEC apoptosis occurring in late Drosophila development involves a mode switching, with isolated single-cell apoptosis transitioning to more clustered apoptosis. Interestingly, genetically knocking down EGFR expression levels resulted in widespread LEC elimination earlier in the developmental process, while overexpressing EGFR led to reduced LEC elimination.     <Figure>  In the early phase of epidermal tissue remodeling precursor cells of adult epidermis called histoblasts proliferate only slowly (top, pink) and cells of larval epidermis should not proliferate rapidly (green). The cells that undergo programed cell death (apoptosis) interact with surrounding cells to prevent premature cell death through the activation of the EGFR/ERK signaling pathway (low and high EGFR/ERK signaling levels are indicated in dark and light colors, respectively). As the tissue remodeling progresses, histoblasts proliferate more rapidly, and the removal of larval epidermal cells has to be accelerated. During this late phase, the up-regulation of EGFR/ERK signaling in the surrounding cells of a dying cells does not occur thereby a group of cells die together. As a consequence, the removal of larval epidermal cells is accelerated. ©Kevin Yuswan     "Further work indicated that decreased activity of extracellular-signal regulated kinase (ERK), a downstream molecule of EGFR, is controlled by the reduced endocytic activity,” explains Daiki Umetsu (Osaka University), senior author of the study. “It also became clear that ERK activity is critical for the apoptotic mode switching.   Specifically, the normal LECs that surround one apoptotic LEC display transiently increased ERK activity, which blocks clustered cell death. However, the reduced endocytic activity prevents this higher ERK activation, causing LEC apoptosis to start occurring in clusters that ultimately results in an accelerated cell elimination rate.   "The field has generally believed that clustered apoptosis poses disadvantages to the organism,” says Yuswan, “Our data contrast this hypothesis by suggesting that clustered apoptosis is required for proper and efficient tissue growth.”   While providing molecular details of tissue remodeling in Drosophila, this study also has wider health implications. This better mechanistic understanding of apoptosis regulation during tissue growth will help determine how abnormal cell death can lead to congenital defects during development.   These findings were published in PLOS Biology on October 14, 2024.     <Publication Details>  Title: Reduction of endocytosis and EGFR signaling is associated with the switch from isolated to clustered apoptosis during epithelial tissue remodeling in Drosophila Authors: Kevin Yuswan, Xiaofei Sun, Erina Kuranaga, Daiki Umetsu Journal: PLOS Biology DOI:  https://doi.org/10.1371/journal.pbio.3002823   Press release  Tohoku University   Press release in Japanese <link: https://www.lifesci.tohoku.ac.jp/date/detail---id-52252.html>   <Contact>  Erina Kuranaga Graduate School of Life Sciences Email: erina.kuranaga.d1(at)tohoku.ac.jp Website:  http://www.biology.tohoku.ac.jp/lab-www/kuranaga_lab/index.html  

https://www.lifesci.tohoku.ac.jp/ 2024-11-11T14:00:00+09:00

One of the most powerful assets of the brain is that it can store information as memories, allowing us to learn from our mistakes. However, some memories remain vivid, while others become forgotten. Unlike computers, our brains appear to filter which memories are salient enough to store.    Researchers from Tohoku University discovered that part of the memory selection process depends on the function of astrocytes, a special type of cell that surrounds neurons in the brain. They showed that artificially acidifying the astrocytes did not affect short-term memory but prevented memories from being remembered long-term.   The findings were detailed in the journal GLIA on November 4, 2024. The researchers implemented a technique called “optogenetics" to manipulate the astrocytes by shining light onto them through optical fibers inserted in the mice's brains. This enabled researchers to directly stimulate and either acidify or alkalinize the astrocytes in that area. They focused on the functions of astrocytes in the amygdala, a brain region known to be crucial for regulating emotion and fear.    A mild electrical shock was delivered to mice in an experiment chamber. When placed back in the same chamber, the mice remembered the shock and froze as a natural response. However, the mice who had their astrocytes acidified immediately after the mild shock were able to temporarily hold onto the fear memory, but they forgot it by the next day. This shows that acidifying the astrocytes did not affect short-term memory but prevented the memories from being remembered long-term.      <Figure 1>  Caption: Selective suppression of long-term memory formation through ChR2 photoactivation of amygdala astrocytes. The experiments suggest the presence of parallel processes governing short-term and long-term memory formation, respectively.  ©Hiroki Yamao, Ko Matsui     A different effect was seen for mice who had their astrocytes alkalinized. When tested three weeks later, control mice typically showed signs of forgetting, demonstrated by a decrease in freezing responses. However, mice whose astrocytes were alkalinized immediately after a strong shock still displayed strong fear responses even after three weeks. This suggests that astrocytes play a key role in determining whether memories are erased or preserved for a long time, immediately after a traumatic event.   While it is generally believed that memories are formed in a continuous process whereby short-term memories gradually solidify and become long-term memories, this research suggests they may actually develop in parallel. "We believe that this could change the way we understand memory formation," says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. He added, "The effect of astrocytes on memory likely also depends on various contexts, including mental, social, or environmental factors."   Lead investigator Hiroki Yamao believes astrocytes could hold the key to understanding emotional changes and memory formation. "This may be just a glimpse of how astrocytes affect emotional information processing," Yamao explains. "Our next goal is to uncover the mechanisms by which astrocytes regulate emotional memory. Understanding these processes could pave the way for therapies that prevent traumatic memories from forming, offering a valuable approach to treating disorders like post-traumatic stress disorder (PTSD) by intervening in memory formation."     <Figure 2>  Caption: Mice inherently possess a selective filtering mechanism that enhances the memory of intense experiences; however, this filtering function was inhibited by ArchT photoactivation of astrocytes in the amygdala. Additionally, the natural forgetting process over three weeks was suppressed by the light stimulation of ArchT-expressing astrocytes. © Hiroki Yamao, Ko Matsui     <Figure 3>  Caption: Astrocytes are capable of triggering fear. Astrocyte ChR2 photoactivation alone induced freezing responses akin to those observed after receiving an electric foot shock. In contrast, astrocyte ArchT photoactivation suppressed the freezing responses following a footshock. © Hiroki Yamao, Ko Matsui     <Publication Details>  Title:    Astrocytic determinant of the fate of long-term memory Authors: Hiroki Yamao, Ko Matsui Journal: GLIA DOI:  https://doi.org/10.1002/glia.24636   Press release  Tohoku University Tohoku University School of Medicine   Press release in Japanese <link: https://www.lifesci.tohoku.ac.jp/research/results/detail---id-52280.html >   <Contact>  Ko Matsui Super-network Brain Physiology, Graduate School of Life Sciences Email: matsui@tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/  

https://www.lifesci.tohoku.ac.jp/ 2024-04-26T11:00:00+09:00

Compared with computers, the brain can perform computations with a very low net energy supply. Yet our understanding surrounding how the biological brain manages energy is still incomplete. What is known, however, is that the dilation and constriction cycles of blood vessels, or vasomotion, spontaneously occur in the brain, a process that likely contributes to enhancing the circulation of energetic nutrients and clearing wasteful materials.   Now, researchers from Tohoku University have developed a method that easily observes and monitors blood vessel dynamics in the mouse brain. This can be done either through the intact skull of a mouse, or deep into the brain using an implanted optical fiber.   The findings were detailed in the journal, eLife, on April 17, 2024.   Since it has been reported that sensory stimuli can cause dilation of blood vessels or hyperemia, researchers sought to induce vasomotion via presenting mice with visual stimuli. What they discovered was when a mouse was shown a horizontally moving stripe pattern that changed direction every 2 to 3 seconds, it caused a reaction in the mouse's blood vessels that matched the pattern's speed.   Mice were presented with 15-minute visual training sessions interleaved with 1-hour resting periods for 4 times per day. With such spaced training, the amplitude of the synchronized vasomotion gradually increased. Interestingly, the visually induced vasomotion was not confined to the area of the cerebral cortex responsible for visual information processing. In other words, synchronized vasomotion spread throughout the whole brain.   “Synchronized vascular motion can be entrained with slowly oscillating visual stimuli,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. “Such enhancement of circulation mechanisms may benefit the information processing capacity of the brain.”   While it's long been known that changes in neuron connections support learning and memory, the plasticity of vasomotion hasn't been described before. Matsui and his colleagues found that a specific visual pattern makes the eyes move more, and this eye movement improvement depends on changes in the brain's cerebellum. The researchers also observed that blood vessel activity in the cerebellum synchronized with this optokinetic motor learning.   Lead study investigator, Daichi Sasaki, believes that synchronized vasomotion, which efficiently delivers oxygen and glucose, could improve learning abilities. He states, "Our next step is to explore the advantages of vasomotion synchronization. It might help clear waste like amyloid beta, potentially delaying or preventing dementia. Stroke recovery could also benefit from better energy supply and waste removal. Additionally, synchronized vasomotion might even enhance intelligence beyond our natural capabilities."   When mice were presented with a horizontal slow oscillation of vertical stripe patterns, vascular dilation and constriction movements that were temporal frequency-locked to the visual stimulus were observed. Such frequency-locked vasomotion was induced not only in the visual cortex but throughout the whole brain. Based on this, vasomotion could increase the efficiency of energy delivery into the brain and also facilitate the clearance of waste materials. Therefore, the researchers hypothesize vasomotion training may result in brain performance enhancement and the treatment of brain disorders. © Daichi Sasaki, Ko Matsui     Vasomotion induced by horizontally oscillating visual stimuli was amplified with training and synchronized throughout the whole brain.   © Daichi Sasaki, Ko Matsui       Parallel occurrence of the learning of horizontal optokinetic response (HOKR) and vasomotion entrainment.   © Daichi Sasaki, Ko Matsui       Publication Details: Title : Plastic vasomotion entrainment Authors : Daichi Sasaki, Ken Imai, Yoko Ikoma, Ko Matsui Journal : eLife DOI : https://doi.org/10.7554/eLife.93721.3   Link Tohoku University   Contact: Ko Matsui, Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University Email: matsui@med.tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/    

https://www.lifesci.tohoku.ac.jp/ 2024-04-19T11:00:00+09:00

Epilepsy, where patients suffer from unexpected seizures, affects roughly 1% of the population. These seizures often involve repetitive and excessive neuronal firing, with the trigger behind this still poorly understood.    Now, researchers at Tohoku University have monitored astrocyte activity using fluorescence calcium sensors, discovering that astrocyte activity starts approximately 20 seconds before the onset of epileptic neuronal hyperactivity. This suggests that astrocytes play a significant part in triggering epileptic seizures, facilitating the hyper-drive of the neural circuit.   The findings were detailed in the journal Glia on April 9, 2024.   Astrocytes are non-neuronal glial cells that occupy almost half of the brain. They have been shown to control the local ionic and metabotropic environment in the brain. Yet, since they do not exhibit electrical activity that can be easily monitored, their role in the function of the brain has largely been neglected. Fluorescence sensor proteins are changing this, revealing more about the mesmerizing activity of astrocytes.   “Astrocytes appear to have a determinant role in controlling the state of neuronal activity and synaptic plasticity both in physiological and pathophysiological situations,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. “Therefore, astrocytes could be considered as a new therapeutic target for epilepsy treatment.”   When brain tissue makes contact with metals such as copper, it is known to induce inflammation that leads to acute symptomatic seizures, which occurs a few times per day in mice. Matsui and his team observed these events, where they discovered that astrocyte activity may be the trigger for neuronal hyperactivity. Astrocytes can also be activated by low-amplitude direct current stimulation. The researchers noticed that such a stimulation induced a robust increase in the astrocyte calcium, which was followed by an epileptic neuronal hyperactivity episode. When the metabolic activity of the astrocytes was blocked by applying fluorocitrate, the magnitude of the epileptic neuronal hyperactivity was significantly reduced. These all point to the fact that astrocytes have the potential to control neuronal activity.   Lead study investigator Shun Araki emphasizes that with appropriate guidance, astrocytes' functions could be harnessed to address a range of neurological conditions. This includes not only epilepsy but also potentially enhancing cognitive abilities beyond natural limitations.          Glial hyper-drive for neuronal control. An optical fiber was implanted into the hippocampus of the brain of the transgenic mouse, which expressed fluorescence calcium sensor protein in astrocytes of the glial cell population. Astrocytes were considered to be silent cells with a minor role in the functioning of the brain. However, with the optical monitoring techniques, the abundance of astrocyte activity is starting to become realized. The researchers were able to capture rare moments of epileptic neuronal hyperactivity using a model of acute symptomatic seizures in mice. The astrocyte calcium elevation started as early as approximately 20 seconds earlier than the neuronal hyperactivity. This suggests that astrocytes trigger the hyper-drive of the neural circuit. © Ko Matsui       Astrocyte activity precedes the onset of epileptic neuronal hyperactivity episodes. (A) With cytosolic calcium ion increase, excitatory actions from astrocytes to neurons are likely to be initiated. These excitatory actions induce a reciprocal excitatory network between neurons, which results in neural circuit oscillations. (B) Calcium in astrocytes started to rise as early as 20 seconds before the onset of neuronal hyperactivity. Neuron-to-astrocyte action is also triggered and reciprocal interactions of neurons and astrocytes occur throughout the epileptic episode. © Ko Matsui       Astrocytes hyper-drive neuronal activity. (A) Passing low amplitude direct current (DC) stimulation resulted in a robust increase in the astrocyte calcium. Several seconds following the astrocyte activation, epileptic neuronal hyperactivity was initiated. (B) Copper implantation in the hippocampus induced acute symptomatic seizures. Fluorocitrate is preferentially taken up into astrocytes and suppresses their metabolic activity. Even in the presence of fluorocitrate, epileptic episodes were observed; however, the magnitude of the hyperactivity was significantly reduced. These results suggest that actions originating from the astrocytes induce epileptic neuronal hyperactivity. © Ko Matsui   Publication Details: Title: Astrocyte switch to the hyperactive mode Authors: Shun Araki, Ichinosuke Onishi, Yoko Ikoma, Ko Matsui Journal: Glia DOI: https://doi.org/10.1002/glia.24537   Link Tohoku University Tohoku University School of Medicine   Contact: Ko Matsui, Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University Email: matsui@med.tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/      

https://www.lifesci.tohoku.ac.jp/ 2024-02-15T15:00:00+09:00

Anxiety is often attributed to an unconscious assessment of the environment and detection of potential danger. Whilst moderate anxiety is therefore advantageous for survival, excessive anxiety can lead to psychiatric disorders.     Now, researchers at Tohoku University have shed light on the intricate interactions between neurons and astrocytes within the habenula, a region of the brain associated with emotional processing. By subjecting mice to a scenario involving a floor scattered with marbles, the researchers observed behavioral responses indicative of anxiety.     The findings were detailed in the journal, Neuroscience Research, on February 10, 2024.     The habenula are a pair of small nuclei located above the thalamus. It is one of the few brain regions that controls both dopaminergic and serotonergic systems. As these neuromodulators play essential roles in a wide range of motivational and cognitive functions, habenula neuronal circuits are potentially relevant to controlling anxiety.     “Anxiety may appear to be an irrational emotion having only negative impacts on our life,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. “However, well-tuned anxiety is a guide provided by our unconsciousness which allows us to navigate the hidden dangers. Such tuning may be accomplished by the actions of the habenula.”     Mice perceive smooth glass marbles as potentially harmful objects due to their unfamiliarity. Mice tend to bury marbles in saw dust bedding to keep these uncomfortable objects out of sight. Here, the researchers created a chamber filled with marbles to create an inescapable, maximum anxiety environment.     They noticed increased neuronal activity in the theta band (5 to 10 Hz) frequency, an increase in local brain blood volume, and acidification occurring in the astrocytes of the habenula when the mice were placed in the all-marble cage. When the habenular astrocytes were artificially alkalized to counter the acidification, the theta band neuronal activity diminished. When the mice were allowed to choose between the brightly lit all-marble cage and a dark and comfortable cage, the mice naturally chose to stay in the dark cage. However, when the habenular astrocytes were optogenetically alkalized, the mice ventured more into the bright cage.     Astrocytes are non-neuronal cells that occupy approximately half of the brain. They have been shown to control the local ionic and metabotropic environment in the brain. Astrocytes also release transmitters that can affect neuronal activity in the vicinity. The results of this study suggest that the theta band habenular neuronal activity is regulated by the activity of astrocytes. Thus, habenular astrocytes were considered to play a role in regulating anxiety.     Lead study investigator, Wanqin Tan, says that future treatment of anxiety disorders may be realized by developing a therapeutic strategy that adjusts astrocyte activity in the habenula. “Habenular astrocytes tune the ‘marble blues.’ Based on this, we expect that methods to cope with anxiety could be developed.”    Habenular astrocytes tuning the marble blues. Mice usually do not prefer novel objects and the presence of smooth glass marbles makes them uneasy and anxious. In the marble burying test, the number of marbles buried in the sawdust bedding is counted and administration of anti-anxiety drugs has been shown to reduce the buried number. However, with the floor filled with marbles, the mouse is faced with inescapable anxiety. Theta-band neuronal activity is observed in the habenula when the mouse is in such an anxiogenic environment. With optogenetic alkalinization of habenular astrocytes, the theta-band neuronal activity becomes dissipated. These experiments suggest the role of habenular astrocytes in regulating the tone of anxiety. * The animal in this figure is not a real photograph but a drawn picture and is depicted for the sole purpose of presenting the circumstantial image of the research only.  ©Wanqin Tan, Ko Matsui       Habenular astrocyte acidification in the anxiogenic environment. (A) Fluorescence sensor protein E2GFP is sensitive to changes in the intracellular pH. The green emission in response to purple light excitation does not change much with changes in the pH; however, the orange emission is largely decreased with pH acidification. E2GFP was selectively expressed in astrocytes and fluorescence fluctuation in the habenula was analyzed using the fiber-photometry method. (B) When the mouse was placed in the anxiogenic all-marble cage, ~ 8 Hz theta-band neuronal activity was detected in the local field potential recorded using a pair of electrodes placed in the habenula. With the optical fiber placed in the habenula, green emission fluorescence showed a downward deflection when the mouse was placed in the all-marble cage. This is the result of an increase in the local brain blood volume. The expansion of the blood vessel diameter likely obstructs the emitted fluorescence from reaching the optical fiber for detection. The orange emission showed a larger downward deflection compared to the green emission. This shows that intracellular pH in the habenular astrocytes was acidified and the local brain blood volume increased when the mice were anxious.  ©Wanqin Tan, Ko Matsui       Optogenetic alkalinization of habenular astrocytes results in the reduction of anxiety. (A) Archaerhodopsin-T (ArchT) is a light-activated outward proton pump. Photoactivation of ArchT expressed in cell membranes results in intracellular alkalinization. ArchT was selectively expressed in astrocytes and the optical fiber placed in the habenula was used for photoactivation of ArchT. When the mouse was placed in an anxiogenic, all-marble cage environment, theta-band neuronal activity was detected. Photoactivation of the ArchT in the habenular astrocytes led to the reduction of the theta-band. (B) Mice normally prefer a dark room with comfortable bedding. When the mouse was placed in a two-way chamber with a dark room and a bright room with an all-marble floor, the mouse tended to stay in the dark room. However, when the ArchT in the habenular astrocytes were photoactivated, the mouse ventured to the bright room and traveled more in the bright room. These results suggest that when the acidic reaction of the habenular astrocytes is countered by optogenetic alkalinization, anxiety can be reduced.  ©Wanqin Tan, Ko Matsui     Publifation Details: Title: Anxiety control by astrocytes in the lateral habenula Authors: Wanqin Tan, Yoko Ikoma, Yusuke Takahashi, Ayumu Konno, Hirokazu Hirai, Hajime Hirase, Ko Matsui Journal: Neuroscience Research DOI: https://doi.org/10.1016/j.neures.2024.01.006 Embargo date: February 10, 2024   Contact: Ko Matsui, Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University Email: matsui@med.tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/

https://www.lifesci.tohoku.ac.jp/ 2024-01-18T09:59:00+09:00

When pathogens attack the body, the innate immune system goes to work protecting against the invading disease. The innate immune system is the first line of defense. It detects precisely what the virus or bacteria is and then activates the proteins that fight the pathogens. Wanting to better understand how the body’s innate immune system works, a team of scientists undertook a study of STING, a protein that plays a vital role in innate immunity. The team provides quantitative results, showing how STING, an acronym for stimulator of interferon genes, works in innate immune signaling.    Their work is published in the journal Nature Communications on Jan 11th, 2024. A graphical illustration of cholesterol- and palmitoylation-dependent STING clustering at the TGN. ©Institute for Glyco-core Research   Type I interferons are signaling proteins that respond when they detect the presence of viruses. They play an essential role in the body’s immune system, communicating between cells as they fight against pathogens. STING is critical for the type I interferon response to pathogen- or self-derived DNA in the cytosol, the fluid portion of a cell. While STING plays an important role in the body’s successful protection against infections, dysregulated STING activity leads to the excessive production of inflammatory mediators that can have a detrimental effect on surrounding cells and tissues. Recent studies have made the connection between STING and a number of autoinflammatory and neurodegenerative diseases.   “STING was discovered as a protein that induces innate immune signals in response to virus-derived non-self DNA. The STING innate immune response has recently been reported to play an important role in cancer immune responses and to contribute to inflammatory pathologies in aging, autoinflammatory, and neurodegenerative diseases, making it a highly attractive target for disease therapy,” said Kenichi G.N. Suzuki, a professor at the Institute for Glyco-core Research, Gifu University and a chief at the Division of Advanced Bioimaging, National Cancer Center Research Institute.                              Research suggests that STING may function as a scaffold to activate the TANK-binding kinase 1 (TBK1). TBK1 is a signaling molecule that is activated by receptors when a viral infection occurs. Scaffold proteins do the important job of regulating key signaling pathways. However, up to this point, scientists have lacked direct cellular evidence proving that STING activated the TBK1.    To analyze the STING cluster, the research team used a live-cell imaging procedure called photoactivated localization microscopy or PALM. They performed this single-molecule imaging of STING with enhanced time resolutions down to 5 milliseconds. They determined that STING becomes clustered at the trans-Golgi network. The trans-Golgi network, or TGN, is a pathway in the body that directs proteins to the correct subcellular destination.   The team also proved that STING palmitoylation facilitated the STING clustering. Palmitoylation describes a protein modification process in the body. This palmitoylation of STING is required for the cluster formation of STING at the TGN. The Golgi lipid order, along with STING palmitoylation, is essential for the STING signaling. The team examined the role of cholesterol, a lipid that plays an essential role in generating the lipid order in STING’s signaling and clustering.   They used a cholesterol biosensor and an environmentally sensitive probe for lipid membranes, to further demonstrate that cholesterol plays a role in the palmitoylated STING-formed clusters that activate TBK1 at the TGN.   The team specifically examined the formation of STING clusters as it relates to COPA syndrome. COPA syndrome is a disorder of immune dysregulation characterized by an increase in type I interferon-stimulated genes. This autoimmune disorder can impact multiple systems in the body.   The team’s imaging of TBK1 revealed that the increase in the clustering enhances the association of TBK1. “We provide quantitative proof-of-principle for the signaling STING scaffold, reveal the mechanistic role of STING palmitoylation in the STING activation, and resolve the long-standing question of the requirement of STING translocation for triggering the innate immune signaling,” said Tomohiko Taguchi, a professor in the Graduate School of Life Sciences, Tohoku University.   Looking ahead, the team sees potential for this work helping the fight against disease. “In the present study, we showed that inhibition of cholesterol transport to TGN markedly suppressed the STING innate immune response. Therefore, based on the results of this study, it is expected that reducing cholesterol levels will be a new tool to treat the diseases associated with STING inflammation,” said Suzuki.   Haruka Kemmoku, Kanoko Takahashi, Kojiro Mukai, Yasunori Uchida, Yoshihiko Kuchitsu, and Tomohiko Taguchi from Tohoku University; Toshiki Mori, Koichiro M. Hirosawa, and Yasunari Yokota from Gifu University; Fumika Kiku and Hiroyuki Arai from the University of Tokyo; Yu Nishioka and Masaaki Sawa from Carna Biosciences, Inc.; Takuma Kishimoto and Kazuma Tanaka from Hokkaido University; and Kenichi G.N. Suzuki from Gifu University and the National Cancer Center, Tokyo.    This work was funded by JSPS KAKENHI, JSPS Research Fellowship for Young Scientists, AMED-PRIME, JST CREST, Subsidy for Interdisciplinary Study and Research concerning COVID-19 (Mitsubishi Foundation), National Cancer Center Research and Development Fund, Takeda Science Foundation, The Uehara Memorial Foundation, Mizutani Foundation for Glycoscience, Daiichi Sankyo Foundation of Life Science, Research Foundation for Opto-Science and Technology, The Naito Foundation, Grant for Basic Science Research Projects from the Sumitomo Foundation, SGH Cancer Research Grant, Research Grant of the Princess Takamatsu Cancer Research Fund, and the Nagoya University CIBoG program from MEXT WISE program.   #   INSERT BOILERPLATE   Suggested EurekAlert! Summary: When pathogens attack the body, the innate immune system goes to work protecting against the invading disease. The innate immune system is the first line of defense. It detects precisely what the virus or bacteria is and then activates the proteins that fight the pathogens. Wanting to better understand how the body’s innate immune system works, a team of scientists undertook a study of STING, a protein that plays a vital role in innate immunity. ### About iGCORE: Institute for Glyco-core Research (iGCORE) is a cutting-edge integrative glycoscience institute that brings together researchers from two universities - Nagoya University and Gifu University under the Tokai National Higher Education and Research System - with outstanding achievements in the fields of glycan synthesis, imaging, glycobiology, and glycomedicine. Through our research, iGCORE is committed to gaining a deeper understanding of the fundamental nature of life, ultimately paving the way for groundbreaking innovations in medicine, such as personalized prevention and early detection of pre-disease.   About The National Cancer Center Research Institute: The National Cancer Center Research Institute is one of the largest cancer research institutions in Japan, with over 350 staff, including postgraduate students and research assistants. The Institute covers 20 research areas with 9 independent units, as well as the Fundamental Innovative Oncology Core, established as a common platform serving the entire Center. From highly original basic research to the development of therapeutic and diagnostic drugs, the Institute conducts a wide range of activities in collaboration with other units within the Center.   Expert Contact： Kenichi G.N. Suzuki, Ph.D., Professor. Institute for Glyco-core Research (iGCORE), Gifu University, Gifu, Japan. Division of Advanced Bioimaging, National Cancer Center Research Institute, Tokyo, Japan. e-mail: suzuki.kenichi.b7@f.gifu-u.ac.jp   Tomohiko Taguchi, Ph.D., Professor. Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan. e-mail: tomohiko.taguchi.b8@tohoku.ac.jp   Media Contact： Yutaka Nibu, Ph.D. Institute for Glyco-core Research (iGCORE), Tokai National Higher Education and Research System yutaka.nibu@igcore.nagoya-u.ac.jp  

https://www.lifesci.tohoku.ac.jp/ 2023-12-13T11:00:00+09:00

People depend on nature in a multitude of ways. Crop pollination, pest management, storm buffering, and carbon capturing are all part of nature’s contributions to people (NCP). But these contributions are subject to change—species that make vital contributions may migrate or even go extinct due to climate change or habitat loss. Forecasting these changes is challenging, but also essential to ensure that humans are adequately prepared to respond.      Part of what makes this so challenging is that current NCP estimates typically rely on data incorporating the physical environment and omit information on species. Given that biodiversity is a cornerstone of NCP, many scientists recognize that biodiversity information can help us better assess the current and future state of NCP.      In a new opinion paper published in Trends in Ecology and Evolution, lead author Jamie M. Kass, associate professor and head of the Macroecology Lab at Tohoku University’s Graduate School of Life Sciences, and an international team of colleagues argue that recent advances in biodiversity modeling and mapping have great potential for improving NCP estimates.     “Modeling and mapping of biodiversity advance at a rapid pace, making it difficult for researchers outside the field to keep up,” points out Kass. “Our paper overviewed the current challenges in predicting NCP and explained how two major biodiversity modeling strategies can help: species distribution models and macroecological models.”      Species distribution models predict species’ range limits and habitat suitability based on environmental variables like climate and land use. Macroecological models also use environmental variables but instead predict biodiversity patterns such as the richness of species in an area or how much ecological communities change across a region.       “In the paper we noted that increased adoption of these modeling strategies could allow for a more reliable assessment of the spatial distribution of NCP, for example, by predicting distributions of service-providing species with high biodiversity likely to be important for NCP,” adds Kass.     To illustrate their point, the authors outlined how multiple advances for these modeling approaches can be employed to predict different dimensions of pollinator diversity, as well as abundance patterns for predators of crop pests and maps of the associated analytical uncertainty.      The authors conclude these advances will help us forecast changes in NCP that human societies rely on and also meet international goals for biodiversity conservation.      The work for this paper was done in partnership with Keiichi Fukaya (National Institute for Environmental Studies, Japan), Wilfried Thuiller (Université Grenoble Alpes, France), and Akira S. Mori (The University of Tokyo).   Edible wild foods like oyster mushrooms (left) and pollination provided by bees (right) are two examples of nature's contributions to people whose distributions can be predicted using biodiversity models. ©Keiichi Fukaya       Example workflows that utilize advances in biodiversity modeling to predict nature’s contributions to people (NCP) linked to species and ecological communities. ©Trend in Ecology & Evolution       Publication Details: Title: Biodiversity modeling advances will improve predictions of nature’s contributions to people Authors: Jamie M. Kass, Keiichi Fukaya, Wilfried Thuiller, Akira S. Mori Journal: Trends in Ecology and Evolution DOI: https://doi.org/10.1016/j.tree.2023.10.011     Contact Name: Jamie M. Kass Affiliation: Tohoku University     Email: kass@tohoku.ac.jp Website: https://www.lifesci.tohoku.ac.jp/en/research/fields/laboratory.html?id=45417 Twitter: ndimhypervol  

https://www.lifesci.tohoku.ac.jp/ 2023-12-05T15:00:00+09:00

Aggression is often associated as a negative emotion. Uncontrolled aggression can lead to conflict, violence and negative consequences for individuals and society. Yet that does not that mean that aggression serves no purpose. It is an instinctive behavior found in many species that may be necessary for survival. The key is managing and channeling aggression.     In a recent study using mice, researchers at Tohoku University have demonstrated that neuron-glial interactions in the cerebellum set the tone of aggression, suggesting that future therapeutic methods could rely on adjusting glial activity there to manage anger and aggression.     The findings were detailed in the journal, Neuroscience Research, on November 24, 2023.     Scientists have recently recognized the role of the cerebellum in non-motor functions such as social cognition. A malfuctioning cerebellum can occur in autism spectrum disorders and schizophrenia, leading to social interaction difficulties. In particular, it has been reported that a region of the cerebellum, known as the vermis, is associated with aggression in humans. Therefore, the researchers investigated the possibility that Bergmann glial cells in the cerebellar vermis regulate the volume of aggression in mice.     Schematic diagram of the mechanism of cerebellar glial cell activity in regulating aggression. Gliotransmitter could be released in response to intracellular Ca2+ concentration increase in the cerebellar Bergmann glial cells. Excitatory transmitters such as glutamate would increase the cerebellar Purkinje cell activity. The only output nerve fiber from the cerebellum is the axon of the Purkinje cell (PC). PC activity leads to inhibitory GABA input to the deep cerebellar nuclei (DCN). Excitatory neuronal contacts from the DCN to the ventral tegmental area (VTA) have recently been identified. Dopaminergic neurons in the VTA have been reported to have a significant influence on social behavior, including aggression. Therefore, if the schematic pathway as described works, then an increase in Ca2+ concentration in cerebellar glial cells would be expected to increase PC activity and suppress DCN and VTA activity, leading to reduced aggression. This could lead to an early breakup of fights. On the other hand, a decrease in Ca2+ concentration in cerebellar glial cells would decrease PC activity and increase DCN and VTA activity, which would increase aggression and lead to dominance in fight situations. ©Yuki Asano, Ko Matsui   “Cells in the brain can be divided into neurons and glia, and although glia occupy approximately half of the brain, their participation in the brain’s information processing, plasticity, and health has long been an enigma,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. “Our newly created fiber photometry method provides a gateway for understanding the physiology of glia.”     Matsui and his colleagues employed the resident-intruder model, where one mouse (the intruder) goes into the territory of another mouse (the resident). When the unfamiliar male mouse enters the cage, quite commonly, a series of fights break out between the resident male mouse and the intruder. Each combat round lasted about 10 seconds, and these rounds were repeated at a frequency of approximately one per minute. The superiority and inferiority of the resident and intruder dynamically switched within each combat round.        Theta band local field potential (LFP) in the cerebellum upon combat breakup. LFPs were recorded between two electrodes implanted in the mouse cerebellum. In the particular combat round shown, the intruder mouse approached the resident mouse (the recorded mouse), and a fight broke out immediately after contact. Signals recorded during the combat were not analyzed as they contained electrical signals from muscle movements from intense exercise. After the combat breaks up, both mice became stationary. The LFPs in the cerebellum showed oscillations in the frequency range of 4 - 6 Hz (theta band). In separate experiments, when theta band electrical stimulation was delivered via the same cerebellar electrode immediately after the start of the fight, the combat often broke up quickly. It was also shown that ChR2 photostimulation of cerebellar glial cells results in theta band LFP in the cerebellum and also causes the fight to break up early. ©Yuki Asano, Ko Matsui   The fiber photometry method revealed that intracellular Ca2+ levels in cerebellar glia decreased or increased in conjunction with the superiority or inferiority of the fight, respectively. When the combat broke up, the researchers observed 4 to 6 Hz theta band local field potentials in the cerebellum, along with a sustained increase in Ca2+ levels in the glia. Optogenetic stimulation of cerebellar glia induced the emergence of the theta band, casuing an early breakup of the fighting.     Glia have been shown to control the local ionic and metabotropic environment in the brain and also to release transmitters that can affect neuronal activity in the vicinity. The results of this study suggest that the theta band cerebellar neuronal activity is regulated by the activity of Bergmann glial cells, thereby demonstrating that cerebellar glial cells play a role in regulating aggression in mice.     Lead study investigator, Yuki Asano, says that future anger management strategies and clinical control of excessive aggression and violent behavior may be realized by developing a therapeutic strategy that adjusts glial activity in the cerebellum. “Imagine a world without social conflict. By harnessing the innate ability of the cerebellar glia to control aggression, the peaceful future could be become reality.”     Fiber optic measurement of the local brain environment of the cerebellum. We measured three types of fluorescence (fYFP, dYFP, and fCFP) by inserting an optical fiber into the cerebellum and sending two types of excitation light. By comparing the three fluorescence waveforms, we can estimate the fluctuation of Ca2+ concentration in glial cells, pH fluctuation, and local brain blood volume. Analysis of Ca2+ concentration fluctuations in glial cells during combats revealed that Ca2+ levels decreased significantly when the recorded resident mice fought back and attacked the intruder mice. When the recorded mice were chased from behind by the intruder mice, Ca2+ in the glial cells increased significantly. In addition, the Ca2+ levels remained high even after the fight broke up. These results suggest that cerebellar glial cell activity is linked to mouse aggression. ©Yuki Asano, Ko Matsui     Publication Details: Title: Glial tone of aggression Authors: Yuki Asano, Daichi Sasaki, Yoko Ikoma, Ko Matsui Journal: Neuroscience Research DOI: https://doi.org/10.1016/j.neures.2023.11.008     Contact: Ko Matsui, Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University Email: matsui@med.tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/      

https://www.lifesci.tohoku.ac.jp/ 2023-09-11T13:00:00+09:00

Researchers have unveiled an intriguing phenomenon of cellular reprogramming in mature adult organs, shedding light on a novel mechanism of adaptive growth. The study, which was conducted on fruit flies (Drosophila), provides further insights into dedifferentiation - where specialized cells that have specific functions transform into less specialized, undifferentiated cells like stem cells.   Until now, dedifferentiation has primarily been associated with severe injuries or stressful conditions, observed during tissue regeneration and diseases like tumorigenesis. However, the researchers have unearthed a previously unknown facet: enteroendocrine cells (EEs) within the intestinal epithelium undergo dedifferentiation into intestinal stem cells (ISCs) in response to nutritional changes, such as recovery from starvation.   “Through meticulous experimentation, we identified a subset of enteroendocrine cells residing in the adult midgut of Drosophila, which exhibit dedifferentiation into ISCs when nutrient levels fluctuate,” states Hiroki Nagai, first author of the study and a postdoc who was previously based at Tohoku University’s Frontier Research Institute for Interdisciplinary Sciences (FRIS). “By utilizing in vivo lineage tracing of EEs and single-cell RNA sequencing, we pinpointed the dedifferentiating EE subpopulation and developed a genetic system for selectively removing ISCs derived from dedifferentiation, a process known as ablation.”     A brief summary of this study: the Drosophila adult midgut rapidly grows in size upon recovery from starvation (adaptive growth). ©Hiroki Nagai et al.     Remarkably, the ablation experiments demonstrated that dedifferentiation is vital for ISC expansion and subsequent intestinal growth following food intake. Previous studies using mice relied on massive stem cell ablation to induce dedifferentiation. Yet, in the current research, stem cells were not lost but instead increased in response to nutritional stimuli. This crucial distinction demonstrates that dedifferentiation is not limited to regenerative contexts but significantly contributes to organ remodeling during environmental adaptations.   Furthermore, the team unraveled the molecular mechanism driving nutrient-dependent dedifferentiation: a deficiency in dietary glucose and amino acids activates the JAK-STAT signaling pathway in EEs, facilitating the conversion of EEs into ISCs during post-starvation recovery. When combined with findings from other studies, this implies that the nutrient-dependent dedifferentiation could be an evolutionary conserved mechanism across species.     A detailed summary of this study: the Drosophila adult midgut rapidly grows in size upon the first food intake after eclosion or upon refeeding after starvation. ©Hiroki Nagai et al.     Yuichiro Nakajima, also formerly based at FRIS and corresponding author of the paper, states that this could lead to being able to control artificial cellular reprogramming in vivo. “If we figure out specific nutrients and the detailed signaling that induce dedifferentiation, we could control cell fate plasticity by nutritional intervention and/or pharmacological treatments”   Looking ahead, they hope to focus on examining cell fate plasticity under physiological conditions beyond nutrition, such as reproduction, temperature, light, and exercise. Doing so may uncover novel mechanisms underlying environmental adaptations.     Representative image of a dedifferentiating EE which is brightly shining like a star.This is a fluorescent confocal microscope image in which the dedifferentiating EE is shown as a cell with white color (center left). Green indicates expression of stemness marker, magenta marks cells that are originally derived from EEs, and blue indicates expression of EE marker. The white color (green + magenta) means that this cell lost identity as EEs and converted into a stem cell. ©Hiroki Nagai et al.   LINK: Tohoku University The Frontier Research Institutes for Interdisciplinary Sciences, Tohoku Univ     Publication Details: Title: Nutrient-driven dedifferentiation of enteroendocrine cells promotes adaptive intestinal growth in Drosophila Authors: Hiroki Nagai, Luis Augusto Eijy Nagai, Sohei Tasaki, Ryuichiro Nakato, Daiki Umetsu, Erina Kuranaga, Masayuki Miura, and Yu-ichiro Nakajima Journal: Developmental Cell DOI: 10.1016/j.devcel.2023.08.022     Contact: Yuichiro Nakajima, Graduate School of Pharmaceutical Sciences, The University of Tokyo Email: nakaji97g.ecc.u-tokyo.ac.jp Website: https://idenut.f.u-tokyo.ac.jp/  

https://www.lifesci.tohoku.ac.jp/ 2023-09-01T09:00:00+09:00

A group of researchers has unearthed the secrets behind a tiny but crucial protein that shuttles zinc ions (Zn2+) within our bodies. The discovery offers a deeper understanding of how our cells maintain optimal health.   Zn2+ may be small, but they play a mighty role in our cells. Zinc enables enzyme catalysis, protein folding, DNA binding, and regulating gene expression, with about 10% of the proteins in our body reliant on Zn2+ to function effectively.   The study, which was published in the journal Nature Communication on August 8, 2023, focused on the Golgi apparatus - a cellular compartment that processes, sorts and distributes cells to their final destination. Within the Golgi, three distinct zinc transporter (ZnT) complexes - ZnT4, ZnT5/6, and ZnT7 - collaborate to usher Zn2+ ions from the cellular interior (cytosol) into the Golgi. While these complexes have long been known to play pivotal roles, the precise mechanisms governing Zn2+ transport within them have remained an enigma.   "We concentrated our study on the transport protein hZnT7," says Kenji Inaba, a corresponding author of the study and professor at Tohoku University's Institute of Multidisciplinary Research for Advanced Materials Sciences. "The study built upon our previous research that hZnT7 plays a vital role in Zn2+ uptake into the cis-Golgi cisterna and regulates the localization, traffic and function of the chaperone protein ERp44."   Cryo-EM map of human ZnT7 in complex with Fab at 2.2 a resolution. ©Han Ba Bui and Kenji Inaba   To reveal more about hZnT7, Inaba and his colleagues employed an advanced technique called cryo-electron microscopy (cryo-EM). Two cryo-EM machines, one from Tohoku University and one from the University of Tokyo, could capture detailed images of hZnT7 in action. By using a Fab fragment from a monoclonal antibody that specifically binds hZnT7 the researchers succeeded in determining the cryo-EM structures of hZnT7 at near-atomic resolutions, gaining critical insights into the mechanisms of Zn2+ transport.   Comparative analysis between hZnT7 and other zinc transporters, including human ZnT8 and bacterial YiiP, exposed distinct structural features of hZnT7. The existence of hZnT7 as a homodimer with varying Zn2+-bound configurations holds particular significance. Notably, hZnT7 boasts an elongated cytosolic histidine-rich loop (His-loop) that interfaces with the transmembrane metal-binding site, a vital feature governing zinc transfer. During Zn2+ recruitment via the His-loop, hZnT7 undergoes intricate conformational rearrangements, shedding light on an unparalleled mechanism of zinc transport.       Conformational transition of the hZnT7 protomer during the Zn2+ transport from the cytosol to the Golgi lumen. ©Han Ba Bui and Kenji Inaba   It is widely known that hZnT7 is a key player in dietary zinc absorption and controlling body fat. When zinc levels drop in certain parts of the body, it can lead to issues like prostate cancer development in mice and disruptions in how our bodies process insulin.   Inaba adds their findings will result in greater understandings of the molecular processes with certain pathogens. "With it reported that abnormalities in Golgi-resident ZnT transporters result in fatal diseases such as diabetes, cancers, and immunodeficiency, it's essential to understand the pathogenic mechanisms of these diseases at the molecular and cellular level."   The histidine-rich loop segment is inserted into the cytosolic cavity and coordinated to Zn2+ at the transmembrane metal-binding site for efficient Zn2+ uptake. ©Han Ba Bui and Kenji Inaba     Publication Details: Title: Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus Authors: Han Ba Bui, Satoshi Watanabe, Norimichi Nomura, Kehong Liu, Tomoko Uemura, Michio Inoue, Akihisa Tsutsumi, Hiroyuki Fujita, Kengo Kinoshita, Yukinari Kato, So Iwata, Masahide Kikkawa & Kenji Inaba Journal: Nature Communications Date of Publication: August 8th, 2023 DOI: 10.1038/s41467-023-40521-5   Link Tohoku University Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Graduate School of Science and Faculty of Science Tohoku University     Contact: Kenji Inaba Institute of Multidisciplinary Research for Advanced Materials Email: kenji.inaba.a1(at)tohoku.ac.jp Website: http://www2.tagen.tohoku.ac.jp/lab/inaba/html/  

https://www.lifesci.tohoku.ac.jp/ 2023-08-24T16:40:00+09:00

https://www.cn.chiba-u.jp/en/news/press-release_e230802/ 2023-08-23T11:00:00+09:00

Researchers have identified a new pathway by which sugar is released by symbiotic algae. This pathway involves the largely overlooked cell wall, showing that this structure not only protects the cell but plays an important role in symbiosis and carbon circulation in the ocean.   The findings were reported in the journal eLife on August 18, 2023.   It is widely known that microalgae enjoy a symbiotic relationship with cnidarians such as corals and sea anemones. The algae use the sun light to produce sugars and other carbohydrates and pass them on to the coral. In return, the coral provides nutrients and shelter to the algae. This fertile coral reefs form in the nutrient-poor tropical oceans and partially addresses the Darwin paradox.     Yet this symbiotic relationship is both delicate and complex; the slightest change in temperature, pollution or water chemistry can have adverse impacts, leading to coral bleaching or other negative effects on the ecosystem. Scientist still do not understand many of the intricate processes at play when it comes to this relationship, but doing so is crucial for the preservation of coral reefs and the biodiversity they support.     “We discovered that the release of sugar occurs when the algal cell begins degrading its own cell wall,” explains Shinichiro Maruyama, lead-author of the research and an associate professor at the University of Tokyo’s Graduate School of Frontier Sciences. “This breakdown of the cell wall happens even when a symbiotic host is absent and gets enhanced when conditions become more acidic.”     Symbiotic algae live in special compartments within coral cells - symbiosomes - or the guts of marine animals. These environments are generally acidic, and the researchers interpret the sugar release as the algal response to environmental changes in nature.     The researchers also found the sugar release is mediated by the enzyme cellulase, which is known for its usage in breaking down the cell walls in land plants. When the alga gets treated with a cellulase inhibitor, the amount of sugar released outside of the cell decreases, indicating that the degradation of sugar chains by cellulase is directly related to the increase in sugar release in acidic conditions.     “Our findings suggest that the algal-coral interaction is more complex than ever thought, providing an important piece of the jigsaw puzzle when it comes to carbon cycling in marine environments,” adds Maruyama.     For their next steps, Maruyama and his team will begin clarifying the molecular mechanisms of sugar release, cell wall maintenance, and regulation of enzymatic reactions. Already, they have embarked on a project to disclose the whole diversity of molecules secreted from symbiotic algae, which will further provide insights into what kind of ‘molecular language’ is exchanged between symbionts and hosts.   Coral reef ecosystem supported by symbiosis with microalgae    A model of the pathways of sugar secretion from coral symbiotic algae     Pocillopora coral in symbiosis with microalgae     Publication Details Title:Environmental pH signals the release of monosaccharides from cell wall in coral symbiotic alga Authors: Yuu Ishii, Hironori Ishii, Takeshi Kuroha, Ryusuke Yokoyama, Ryusaku Deguchi, Kazuhiko Nishitani, Jun Minagawa, Masakado Kawata, Shunichi Takahashi, Shinichiro Maruyama* Journal: eLife DOI: https://doi.org/10.7554/eLife.80628   Link Tohoku University Graduate School of Science and Faculty of Science Tohoku University Graduate School of frontier sciences, the University of Tokyo     Contact Name: Shinichiro Maruyama Affiliation: Laboratory of Integrated Biology Department of Integrated Biosciences Graduate School of Frontier Sciences The University of Tokyo Email: shinichiro.maruyama@k.u-tokyo.ac.jp Website: https://www.ib.k.u-tokyo.ac.jp/english/faculty/integrated_biology/      

https://www.lifesci.tohoku.ac.jp/ 2023-06-27T12:00:00+09:00

Researchers at Tohoku University have discovered that there are two parallel processes involved in memory formation when a mouse performs a motor learning task. One process occurs during training and is called online learning, while the other happens during the resting period and is called offline learning. Online learning can be boosted or reduced by manipulating glial activity, but offline learning remains unaffected by these manipulations. Understanding the cellular mechanisms underlying these independent parallel memory formation processes may lead to the development of efficient rehabilitation after strokes, dementia treatment, or realizing extended intelligence.   The findings were detailed in the journal Glia on June 26, 2023.   We have long been aware that performance may not improve much during training, but increase the next day. Alternatively, excelling during training may not carry over to the next day. Here, the researchers have shown that online and offline learning are indeed separate parallel processes governed by distinct cellular mechanisms.   Glial cells in the brain occupy almost as much volume as neurons; however, they were simply thought to fill the gaps between neurons. Recently, glial cells have been shown to be involved in the information processing in the brain, albeit in quite a different manner than that of neurons. By releasing gliotransmitters, such as glutamate, glial cells can modulate the easiness of memory formation; a process termed meta-plasticity.   The researchers used the horizontal optokinetic response paradigm to understand the role of glial cells in online and offline learning. When mice were presented with a horizontally oscillating visual stimulus, their eyes followed the screen with a lesser amplitude relative to the presented stimulus. With prolonged and repeated presentation, the amplitude increased until their eyes could perfectly pursue the screen. The performance increase during the 15 min presentation was termed online learning and the increase during the 1-hour resting period, which the mice spent in the dark, was termed offline learning.     Parallel memory processing hypothesis. When a mouse is presented with an image that oscillates left and right, the mouse initially cannot follow the image well, but after repeated training, the visual pursuit of the image becomes more accurate. In this study, it was shown that there is online learning that progresses during training and offline learning that progresses slowly during post-training rest and that the function of glial cells in the brain is involved in each learning process. ©Teppei Kanaya, Ko Matsui     Light-activated proteins, channelrhodopsin-2 (ChR2) or archaerhodopsin (ArchT) were genetically expressed specifically in glial cells to manually control glial activity. When glutamate release from glial cells was facilitated by photo-activating ChR2, online learning was augmented. However, the benefit from glial modulation was short-lasting and the performance of eye movement soon became indistinguishable from control. When the glial activity was inhibited by ArchT, online learning was completely suppressed. Interestingly, offline learning proceeded normally even in the complete absence of online learning.   “Our data shows that short- and long-term memory formation is not a serial process, but rather it is a parallel and independent process,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. “Agonizing over the performance gained during each training or study session is unnecessary, as long-lasting achievement depends on a totally separate process.”   The cellular mechanisms underlying glial modulation of online learning are now partially uncovered. Anion conducting channels expressed in glial cells mediate glutamate release, which leads to the augmentation of synaptic plasticity. The process of offline learning is less clear; however, the researchers have also found that ArchT optogenetic manipulation of glial activity during the resting period could facilitate offline learning.   “Glial cells apparently control the likelihood of plasticity to occur in the neural circuits, either during the online or offline learning process,” says the lead study investigator, Dr. Teppei Kanaya. “By uncovering the details of the cellular process, we may be able to control our rapid adaptation to changes in the environment or facilitate long-term achievements.”         Optical glial control of learning and memory. Optogenetic control of glial cell function in the brain during training could either enhance or inhibit online learning performance. Interestingly, regardless of the degree of online learning, offline learning was shown to progress at the same rate as the control group. The results indicate that online and offline learning are independent and parallel processes of memory formation. ©Teppei Kanaya, Ko Matsui       Cellular mechanisms of parallel memory formation. Both online learning, which proceeds during training, and offline learning, which proceeds during rest, are triggered by training. Offline learning proceeds slowly, independently, and in parallel with online learning. Using optogenetics technology to optically manipulate glial function, it has been shown that the amount of glutamate released from glial cells determines the degree of online learning. In addition, optical stimulation of ArchT expressed in glial cells during offline rest was shown to enhance offline learning. The degree of offline learning is controlled by a mechanism other than online learning. Glial cells appear to be involved in both online and offline learning. ©Teppei Kanaya, Ko Matsui       Publication Details Title: Glial modulation of the parallel memory formation Authors: Teppei Kanaya, Ryo Ito, Yosuke M. Morizawa, Daichi Sasaki, Hiroki Yamao, Hiroshi Ishikane, Yuichi Hiraoka, Kohichi Tanaka, and Ko Matsui Journal: Glia DOI: https://doi.org/10.1002/glia.24431   Contact Name: Ko Matsui Affiliation: Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University Email: matsui@med.tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/

https://www.lifesci.tohoku.ac.jp/ 2023-05-29T14:00:00+09:00

 A research group has unearthed how zinc transporter complexes regulate zinc ion (Zn2+) concentrations in different areas of the Golgi apparatus and revealed that this mechanism finely tunes the chaperone protein ERp44.   The findings, which were reported in the journal Nature Communications on May 9, 2023, reveal the crucial chemical and cellular biological mechanism at play behind zinc homeostasis, something necessary for avoiding fatal diseases such as diabetes, cancers, growth failures, and immunodeficiency.   As a trace element, zinc is essential for our health. Zn2+ are vital for enzyme catalysis, protein folding, DNA binding, and regulating gene expression, with nearly 10% of human proteome binding Zn2+ for their structural maturation and function.   Secretory proteins like hormones, immunoglobulins, and blood clotting factors are synthesized and folded in the endoplasmic reticulum (ER), a complex membrane network of tubules. Subsequently, they are transported to and matured in the Golgi apparatus, the organelle composed of multiple flattened sacs called cisternae, which sorts and processes proteins before directing them to a specific destination. Chaperone proteins are vital for maintaining protein homeostasis and preventing the formation of misfolded or aggregated proteins in these organelles.   The group’s previous research demonstrated that Zn2+ in the Golgi apparatus plays an essential part in protein quality control in the early secretory pathway comprising the ER and Golgi. This system is mediated by the ER-Golgi cycling chaperone protein ERp44.   In the Golgi apparatus, there exists three ZnT complexes: ZnT4, Znt5/6, and ZnT7. Yet, until now, mechanisms of how Zn2+ homeostasis is maintained in the Golgi apparatus has remained unclear.   “Using chemical biology and cell biology approaches together, we revealed that these ZnT complexes regulate the Zn2+ concentrations in the different Golgi compartments, namely cis, medial, and trans-Golgi cisternae,” says Kenji Inaba, a corresponding author of the study and professor at Tohoku University’s Institute of Multidisciplinary Research for Advanced Materials Sciences. “We also further elucidated the intracellular transport, localization, and function of ERp44 controlled by ZnT complexes.”     A fluorescence image of the ER and Golgi apparatus. Authors revealed that the Golgi-resident zinc transporters, ZnT4, ZnT5/6, and ZnT7, serve to maintain zinc homeostasis at the different Golgi cisternae. This mechanism finely tunes the localization, traffic and function of the ER-Golgi-cycling chaperone protein, ERp44. ©Yuta Amagai et al.       ERp44 captures immature secretory proteins at the Golgi apparatus to prevent their abnormal secretion. Previous studies have shown that mice with the expression of ERp44 suppressed suffer from heart failure and hypotension.   Additionally, many secretory zinc enzymes are related to various diseases, including metastasis of cancer cells and hypophosphatasia. These enzymes depend on the Golgi-resident ZnT complexes to acquire Zn2+ for enzymatic activity. Male mice with ZnT5 suppressed have experienced death caused by arrhythmias, so there is possible relevance of Zn2+ homeostasis to cardiovascular disease.   “Our findings will help us understand the mechanism by which disruptions of Zn2+ homeostasis in the early secretory pathway leads to the development of pathological conditions,” adds Inaba. The group are hopeful that the strategies employed in their study can paint a bigger picture of the mechanisms underlying the maintenance of intracellular Zn2+ homeostasis, recommending future studies that can measure Zn2+ in other organelles such as the mitochondria and nucleus.   The group are hopeful that the strategies employed in their study can paint a bigger picture of the mechanisms underlying the maintenance of intracellular Zn2+ homeostasis, recommending future studies that can measure Zn2+ in other organelles such as the mitochondria and nucleus.     <Publication Details> Title: Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface Authors: Y. Amagai, M. Yamada, T. Kowada, T. Watanabe, Y. Du, R. Liu, S. Naramoto, S. Watanabe, J. Kyozuka, T. Anelli, T. Tempio, R. Sitia, S. Mizukami, and K. Inaba*. Journal: Nature Communications DOI: 10.1038/s41467-023-38397-6   <Link> Tohoku University   <Contact> Kenji Inaba Institute of Multidisciplinary Research for Advanced Materials Email: kenji.inaba.a1@tohoku.ac.jp Website: http://www2.tagen.tohoku.ac.jp/lab/inaba/html/  

https://www.lifesci.tohoku.ac.jp/ 2023-04-11T13:00:00+09:00

    Decades’ worth of research has shown that the motivation to feed, i.e., hunger and feelings of fullness, is controlled by hormones and small proteins called neuropeptides. They are found in a wide array of organisms like humans, mice and fruit flies. Such a widespread occurrence suggests a common evolutionary origin. To explore this phenomenon, a research group has turned to jellyfish and fruit flies, discovering some surprising results.      　Although jellyfish shared a common ancestor with mammals at least 600 million years ago, their bodies are simpler; they possess diffused nervous systems called nerve nets, unlike mammals which have more concrete structures such as a brain or ganglia. Still, jellyfish possess a rich repertoire of behaviors, including elaborate foraging strategies, mating rituals, sleep and even learning. Despite their important position in the tree of life, these fascinating creatures remain understudied, and almost nothing is known about how they control their food intake.      　The group, which was led by Hiromu Tanimoto and Vladimiros Thoma from Tohoku University’s Graduate School of Life Sciences, focused on Cladonema, a small jellyfish with branched tentacles that can be raised in a laboratory. These jellyfish regulate how much they eat based on how hungry they are.   The jellyfish Cladonema pacificum. ©Hiromu Tanimoto   　“First, to understand mechanisms underlying feeding regulation, we compared the gene expression profiles in hungry and fed jellyfish,” said Tanimoto. “The feeding state changed the expression levels of many genes, including some that encode neuropeptides. By synthesizing and testing these neuropeptides, we found five that reduced feeding in hungry jellyfish.”     　The researchers then honed in on how one such neuropeptide—GLWamide—controls feeding. A detailed behavioral analysis revealed that GLWamide inhibited tentacle shortening, a crucial step for transferring captured prey to the mouth. When the researchers labelled GLWamide, they found it was present in motor neurons located in the tentacle bases, and feeding increased GLWamide levels. This led to the conclusion that, in Cladonema, GLWamide acts as a satiety signal - a signal sent to the nervous system indicating that the body has had enough food.   The GLWamide (green) expressed in neurons surrounding the Cladonema eyelet (black circle). Nuclei shown in magenta. ©Vladimiros Thoma et al.   　Yet the researchers’ quest to explore the evolutionary significance of this finding did not stop there. Instead, they looked to other species. Fruit flies’ feeding patterns are regulated by the neuropeptide myoinhibitory peptide (MIP). Fruit flies lacking MIP eat more food, eventually becoming obese. Interestingly, MIP and GLWamide share similarities in their structures, suggesting they are related through evolution.     　“Since the functions of GLWamide and MIP have been conserved despite 600 million years of divergence, this led us to ponder whether it was possible to exchange the two,” said Thoma. “And we did exactly that, first giving MIP to jellyfish and then expressing GLWamide in flies that had no MIP.”     　Amazingly, MIP reduced Cladonema feeding, just as GLWamide had. Furthermore, the GLWamide in flies eliminated their abnormal over-eating, pointing to the functional conservation of the GLWamide/MIP system in jellyfish and insects.     　Tanimoto notes that their research highlights the deep evolutionary origins of a conserved satiety signal and the importance of harnessing a comparative approach. “We hope that our comparative approach will inspire focused investigation of the role of molecules, neurons and circuits in regulating behavior within a wider evolutionary context.”   Publications Details: Title: On the origin of appetite: GLWamide in jellyfish represents an ancestral satiety neuropeptide Authors: Vladimiros Thoma, Shuhei Sakai, Koki Nagata, Yuu Ishii, Shinichiro Maruyama, Ayako Abe, Shu Kondo, Masakado Kawata, Shun Hamada, Ryusaku Deguchi, Hiromu Tanimoto Journal: The Proceedings of the National Academy of Sciences (PNAS) DOI: https://doi.org/10.1073/pnas.2221493120   Link Tohoku University   Contact: Hiromu Tanimoto Graduate School of Life Sciences, Tohoku University Email: hiromut(at)m.tohoku.ac.jp Website: http://www.lifesci.tohoku.ac.jp/neuroethology/index.html    

https://www.lifesci.tohoku.ac.jp/ 2023-03-31T16:00:00+09:00

Asexual, or vegetative, reproduction in plants is controlled by environmental conditions, but the molecular signaling pathways that control this process are poorly understood. Recent research suggests that the KAI2-ligand (KL) hormone is responsible for initiating and terminating the production of gemmae, or genetically identical plantlets, on liverwort plants based on the presence or absence of specific environmental factors.   A team of leading scientists from Tohoku University designed a research study to investigate the hormones and signaling pathways associated with vegetative reproduction in the liverwort plant Marchantia polymorpha. Through a series of gene knockout (loss of function) experiments, the researchers demonstrated that the MpKARRIKIN INSENSITIVE2 (MpKAI2)-dependent signaling pathway initiates gemma cup, the structure that surrounds gemmae plantlets, and gemmae formation in liverwort plants, and that KAI2-dependent signaling, initiated through KL hormone binding, determines the total number of gemmae produced in a gemma cup. The team additionally observed that switching off KAI2-dependent signaling in the liverwort plant stops gemma production through the accumulation of MpSMXL, a suppressor protein.   The team published the results of their study on March 1, 2023 in the journal Current Biology.   "We discovered that the plant hormone KAI2-ligand, KL, is a gemma initiation hormone, and the efficiency of vegetative reproduction is regulated by modulating KL signaling according to environmental conditions," said Junko Kyozuka, one of the research paper authors and professor at the Graduate School of Life Sciences at Tohoku University. Interestingly, the KL hormone has yet to be identified, but researchers have inferred its presence based on its ability to bind and activate the KARRIKAN INSENSITIVE2 (KAI2) signaling pathway.     Vegetative reproduction of M. polymorpha is controlled by KL signaling. KL works as a plant hormone inducing gemma initiation and controls the efficiency of vegetative reproduction by switching the KAI-dependent signaling pathway on and off. ©Komatsu et al.     Through their research, the team discovered that normal, wild-type liverwort plants consistently produce the same number of gemmae given the same environmental conditions, suggesting a genetic basis for this trait. The researchers discovered that KAI2-dependent signaling, initiated by KL binding, starts the process of gemma formation by breaking down the MpSMXL suppressor protein. Once the proper number of gemmae is produced, KAI2-dependent signaling is turned off, and the MpSMXL suppressor protein accumulates again, turning off gemma formation.   "Because vegetative reproduction is widespread in plants, this discovery also elucidates the origin of vigorous growth pattern[s] of plants," added Kyozuka. Importantly, the team also revealed the direction that gemmae are initiated in the gemma cup, which starts from the inner region of the gemma cup and moves out to the periphery.   In KL signaling (A), KAI2 functions as a receptor of an unknown plant hormone called KL. After binding with KL, KAI2 forms a complex with MAX2, an F-box protein, and SMXL, a repressor protein. SMXL is degraded by MAX2, leading to the de-repression of genes that were suppressed by SMXL, resulting in various responses. In KAI2 and MAX2 loss-of-function mutants (B), KL signaling does not occur, and gemma cups are not formed. In SMXL loss-of-function mutants (C), genes suppressed by SMXL are no longer repressed, mimicking KL signaling, and more gemmae are formed.©Komatsu et al.     While the current study has answered many important questions related to vegetative reproduction in the liverwort plant, many questions remain. The identity of the KL hormone remains unknown, and the environmental conditions responsible for KL regulation, and thus KAI2-dependent signaling, remain a mystery. The research team experimented with liverwort growth medium that lacked potassium (K), nitrate (N) or phosphorus (P) to observe the effect of nutrient deprivation on gemmae formation, but no effect was seen on normal, wild-type liverwort plants. The team plans to design future studies to determine the environmental factors that influence KL regulation and their individual effects.   The mechanisms that dictate when gemma formation stops in liverwort plants also remain unknown. The research team removed gemmae from gemma cups that were actively producing gemmae and found that removal of gemmae didn't affect the timing of gemma initiation termination (roughly 10 days) or the total number of gemmae formed in the cup. This result suggested that the timing, rather than the number of gemmae in a gemma cup, is more likely to determine when gemma initiation ceases. However, the researchers could not rule out a role for gemmae quantity in the termination of gemmae initiation. The team plans to more fully investigate both hypotheses in future studies.   Other contributors include Aino Komatsu, Kyoichi Kodama, Yohei Mizuno and Mizuki Fujibayashi from the Graduate School of Life Sciences at Tohoku University in Sendai, Japan; and Satoshi Naramoto from the Graduate School of Life Sciences at Tohoku University in Sendai, Japan and the Department of Biological Sciences at Hokkaido University in Sapporo, Japan.       Marchantia polymorpha propagates through vegetative reproduction by forming gemmae in a gemma cup. Each gemma in gemma cups grows to a thallus, on which more gemma cups are formed. By repeating this process, Marchantia polymorpha can propagate vigorously. ©Komatsu et al.       Publications Details: Title: Control of vegetative reproduction in Marchantia polymorpha by the KAI2-ligand signaling pathway Authors: Aino Komatsu, Kyoichi Kodama, Yohei Mizuno, Mizuki Fujibayashi, Satoshi Naramoto, Junko Kyozuka Journal: Current Biology DOI: https://www.sciencedirect.com/science/article/abs/pii/S0960982223001628     Contact: Junko Kyozuka Graduate School of Life Sciences, Tohoku University Email: junko.kyozuka.e4(at)tohoku.ac.jp Website: https://www.lifesci.tohoku.ac.jp  

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