Latest news. https://www.lifesci.tohoku.ac.jp/ Graduate School of Life Sciences, Tohoku University 2026-02-17T13:00:00+09:00

【Title】 Ketamine Engages a Brain–Body Pathway to Prevent Endotoxemic Death   【Date】 March 11, 2026 (Wednesday) 4:30 PM–6:00 PM   【Venue】 Conference Room 103, Graduate School of Life Sciences,  Life Sciences Project Research Laboratory Building, Katahira Campus   【Speaker】 Jose G. Grajales, MD, PhD Yale School of Medicine   【Abstract】 Acute systemic inflammatory response induced by bacterial products, such as lipopolysaccharide (LPS), results in dramatic changes in organismal physiology that can culminate in death. Multiple factors can contribute to endotoxemia-associated mortality, including direct inflammatory damage to vital organs, hemodynamic shock, and multiple organ failure1. Here, we explored the role of brain-body communication in the setting of acute systemic inflammatory response. We found that the common anesthetic drug, ketamine, prevented LPS-induced mortality. Ketamine also prevented death from direct TNF-administration, suggesting that survival was not depended solely on lowering systemic cytokines. Detailed systemic profiling reveals that ketamine induced a neuroprotective state characterized by restored heat production, preserved arousal networks, and faster recovery from systemic hypometabolism sixteen hours after treatment. Importantly, peripheral administration of a blood–brain barrier (BBB)–impermeant NMDA antagonist analog does not prevent death. Conversely, central administration of the same analog mimics the survival benefit of systemic ketamine, demonstrating that the NDMA antagonism in the CNS is sufficient to protect mice from LPS-induced mortality. These findings suggest a brain-to-body survival circuit, which restores metabolic balance and impacts survival after inflammatory shock. Our research redefines ketamine’s mechanism of action, positioning it as a key neuroimmune modulator at the CNS that transforms a deadly metabolic collapse into a recoverable physiological state.     Cell type-specific dissection of sensory pathways involved in descending modulation. Nguyen E, Grajales-Reyes JG, Gereau RW 4th, Ross SE. Cell type-specific dissection of sensory pathways involved in descending modulation. Trends Neurosci 2023, 46: 539-550.   Wireless multilateral devices for optogenetic studies of individual and social behaviors. Yang Y, Wu M, Vázquez-Guardado A, Wegener AJ, Grajales-Reyes JG, Deng Y, Wang T, Avila R, Moreno JA, Minkowicz S, Dumrongprechachan V, Lee J, Zhang S, Legaria AA, Ma Y, Mehta S, Franklin D, Hartman L, Bai W, Han M, Zhao H, Lu W, Yu Y, Sheng X, Banks A, Yu X, Donaldson ZR, Gereau RW, Good CH, Xie Z, Huang Y, Kozorovitskiy Y, Rogers JA. Wireless multilateral devices for optogenetic studies of individual and social behaviors. Nature Neuroscience 2021, 24: 1035-1045.   Surgical implantation of wireless, battery-free optoelectronic epidural implants for optogenetic manipulation of spinal cord circuits in mice. Grajales-Reyes JG, Copits BA, Lie F, Yu Y, Avila R, Vogt SK, Huang Y, Banks AR, Rogers JA, Gereau RW, Golden JP. Surgical implantation of wireless, battery-free optoelectronic epidural implants for optogenetic manipulation of spinal cord circuits in mice. Nature Protocols 2021, 16: 3072-3088.   Cell type-specific modulation of sensory and affective components of itch in the periaqueductal gray. Samineni VK, Grajales-Reyes JG, Sundaram SS, Yoo JJ, Gereau RW. Cell typespecific modulation of sensory and affective components of itch in the periaqueductal gray. Nature Communications 2019, 10: 4356.     Contact Sho Aoki：　sho.aoki.d3(at)tohoku.ac.jp

https://www.lifesci.tohoku.ac.jp/ 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/ 2025-05-01T00:00:00+09:00

Course outline 2025 has been updated. Please see below.       Graduate school of life sciences, Tohoku University 2025 (13.0MB) (Written in both Japanese & English)      

https://www.lifesci.tohoku.ac.jp/ 2025-04-17T15:00:00+09:00

【開催日時・Date】 2025.5.13(TUE) 16:00～   【講師・Speaker】 明楽隆志博⼠（Dr. Takashi Akera） ⽶国国⽴衛⽣研究所 NIH (National Institute of Health)   【会場・Venue】 ハイブリッド開催（Hybrid） 片平・生命科学プロジェクト研究棟講義室AB Life Sciences Project Research Laboratory, Lecture hall   【事前登録・Pre-registration】 Zoom link https://us06web.zoom.us/meeting/register/WLlLNgYET0iOM-qP2KkOIg   【使用言語・Language】 English   【題目・Title】 ＜第⼀部＞ 16:00~17:10 The impact of non-Mendelian transmission on reproduction and speciation メンデルの法則に反する遺伝様式が有性⽣殖と種分化に与える影響   Abstract: Mendel’s Law of Segregation states that each allele has an equal chance to transmit to the next generation. However, this law can be violated by selfish genetic elements, which manipulate the production of gametes (e.g., eggs, sperm) to increase their own transmission rate. This genetic cheating in meiosis, meiotic drive, has significant impacts on Genetics, Evolution, and Reproduction because the cheating alters transmission ratios and manipulates gametogenesis, often leading to fertility issues and genetic disorders (e.g., Down Syndrome). In female meiosis, selfish elements bias their transmission by preferentially segregating to the egg. However, it remains largely unknown how these elements bias their segregation to the egg especially in animals. My lab uses mouse models and cell biological approaches to visualize selfish elements to reveal how these elements manipulate female meiosis to preferentially segregate to the egg. I will discuss our recent findings on the mechanisms of meiotic drive and how it impacts mammalian reproduction and speciation. References: Clark FE, Akera T., et.al, . An egg sabotaging mechanism drives non-Mendelian transmission in mice. Curr Biol. 9;34(17):3845-3854 (2024) El Yakoubi W and Akera T. Condensin dysfunction is a reproductive isolating barrier in mice. Nature 623(7986):347-355 (2023)   ＜第⼆部＞A career talk 17:10~18:00 ~pursuing a childhood dream of going to space, while running a lab in the US~ 海外独⽴そして宇宙への挑戦   Abstract: Career path after acquiring a PhD degree is becoming increasing diverse. During this and Europe to launch my own laboratory. While pursuing basic science in the lab, I never forgot my childhood dream to go to space. I will also discuss how I balanced my real life as a PI while applying for the astronaut position to achieve my dream and what I eventually got from this experience even though I was not selected. I wish this presentation would provide some hope to junior scientists who are deciding their career trajectories.   PDF   Contact 生命科学研究科　発生ダイナミクス分野 Grad. Sch. of Life Sciences, Developmental Dynamics 杉本亜砂子 Asako Sugimoto E-mail：asako.sugimoto.d1(at)tohoku.ac.jp  

https://www.lifesci.tohoku.ac.jp/date/seminar/detail---id-47395.html 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/ 2025-03-04T17:00:00+09:00

Date Wednesday, March 26, 2025 – Friday, March 28, 2025   Venue Sendai Ryokusaikan Visitor Center [Access]   Invited Speakers *Shinsuke Shimojo (California Institute of Technology) *Sven Bestmann (University College London) *Wen–Sung Lai (National Taiwan University) *Alison E Lane (La Trobe University) Ko Matsui (Tohoku University) Kentaro Abe (Tohoku University) Ken–Ichiro Tsutsui (Tohoku University) Takuya Sasaki (Tohoku University) Keiichi Kitajo (National Institute for Physiological Sciences) Ayuko Hoshino (The University of Tokyo) Noriko Osumi (Tohoku University) Yukie Nagai (The University of Tokyo) Masahiki Inami (The University of Tokyo) Fumitaka Homae (Tokyo Metropolitan University) Masanori Hariyama (Tohoku University) Shin–ichiro Kumagaya (The University of Tokyo) Motoaki Nakamura (Showa University) Saku Hara (Tohoku University)   * keynote speaker   Registration Registration deadline: Friday, March 7, 2025, 16:00 (JST) Registration Form   Time Schedule     Wednesday, March 26, 2025   12:20 – 13:00 Registration open 13:00 – 13:05 Opening remarks Ken–Ichiro Tsutsui (Tohoku Univ.) 13:05 – 13:40 Ken–Ichiro Tsutsui (Tohoku Univ.) TBA 13:40 – 14:15 Takuya Sasaki (Tohoku Univ.) TBA 14:15 – 14:50 Ko Matsui (Tohoku Univ.) TBA 14:50 – 15:20 Coffee break 15:20 – 15:55 Keiichi Kitajo (NIPS) TBA 15:55 – 16:40 Sven Bestmann (UCL) TBA   Thursday, March 27, 2025   13:00 – 13:35 Masahiko Inami (Univ. Tokyo) TBA 13:35 – 14:10 Masanori Hariyama (Tohoku Univ.) TBA 14:10 – 14:45 Yukie Nagai (Univ. Tokyo) TBA 14:45 – 14:50 Group photo 14:50 – 15:20 Coffee break 15:20 – 15:55 Kentaro Abe (Tohoku Univ.) TBA 15:55 – 16:30 Fumitaka Homae (Tokyo Met. Univ.) TBA 16:30 – 17:15 Shinsuke Shimojo (Caltech) TBA 18:30 – 20:30 Get together dinner   Friday, March 28, 2025 10:00 – 10:35 Ayuko Hoshino (Univ. Tokyo) TBA 10:35 – 11:10 Noriko Osumi (Tohoku Univ.) TBA 11:10 – 11:45 Motoaki Nakamura (Showa Univ.) TBA 11:45 – 13:00 Lunch 13:00 – 13:45   Alison E Lane (La Trobe Univ.) TBA 13:45 – 14:20 Shinichiro Kumagaya (Univ. Tokyo) TBA 14:20 – 14:40 Coffee break 14:40 – 15:15 Saku Hara (Tohoku Univ.) TBA 15:15 – 16:00 Wen–Sung Lai (Nat. Taiwan Univ.) TBA 16:30 – 17:15 Closing remarks Noriko Osumi (Tohoku Univ.)   Poster -Download [PDF]   Organizers   Ken–Ichiro Tsutsui (Tohoku University)   Noriko Osumi (Tohoku University)   Co–hosted by Neuro Global International Joint Graduate Program Graduate School of Life Sciences, Tohoku University Tohoku University School of Medicine Tohoku University Brain Science Center Moonshot Goal 9 National Research Program for Neurological Disorders and Mental Health Multidisciplinary Frontier Brain and Neuroscience Discoveries  Contact Email: office*snlabsendai.org (change * to @)

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/ 2024-10-08T00:00:00+09:00

Program Theme Human beings have a fundamental need to communicate, belong to society, and achieve self–actualization through social interactions. Isolation can lead to disorders like depression and adjustment disorder. The rapid diversification of values and lifestyles has made many people societal minorities, increasing difficulties in living, working, or learning. This program aims to foster interdisciplinary collaboration among neuroscience, informatics, and robotics researchers. It seeks to understand the mind and develop new communication aids to help people connect. The program will significantly impact society by promoting social inclusion and diversity, and scientifically, it will benefit each field by integrating complementary technologies to study and interact with the human mind.   Events Social Memory: Neural Basis of Communication, Part 1 (September 5, 2024 – September 6, 2024)   Reward, Motivation, and Beyond: Neural Basis of Communication, Part 2 (October 14, 2024)   Towards the Future of Communication: Creating an Inclusive World with Neuro/Bioscience and Engineering Technologies (March 26, 2025 – March 28, 2025)   Organizers Ken–Ichiro Tsutsui (Professor, Graduate School of Life Sciences, Tohoku University)   Noriko Osumi (Professor, Tohoku University Graduate School of Medicine)   Hosted by Tohoku Forum for Creativity   Co–hosted by Neuro Global International Joint Graduate Program Graduate School of Life Sciences, Tohoku University Tohoku University Graduate School of Medicine Tohoku University Brain Science Center Moonshot Goal 9 National Research Program for Neurological Disorders and Mental Health Multidisciplinary Frontier Brain and Neuroscience Discoveries   Poster Part1 (PDF) Poster Part2 (PDF)   Link Tohoku Forum for Creativity

https://www.lifesci.tohoku.ac.jp/ 2024-09-02T11:00:00+09:00

【開催日時・Date】 2024.9.13(Fri) 16:00～17:30   【講師・Speaker】 Dr. Andre Pires da Silva School of Life Sciences, University of Warwick, UK   【会場・Venue】ハイブリッド開催（Hybrid） 片平・生命科学プロジェクト研究棟講義室AB Life Sciences Project Research Laboratory, Lecture hall   【事前登録・Pre-registration】 Zoom link https://zoom.us/meeting/register/tJwpcu2upjotHdH6Efme17Rem5kDJO3AaQoP   【使用言語・Language】 English   【題目・Title】 Evolution of sex determination and sex-ratio bias   【要旨・Abstract】 Sex-determining mechanisms are characterized by their rapid evolution and diversity even among populations of the same species. We focus on the study of sex determination in free-living nematodes of the genus Auanema, revealing the mechanisms that control the development of males, females, and hermaphrodites. Intriguing findings emerged from crossing different sexual morphs: matings between hermaphrodites and males yield only male progeny, while crosses between males and females produce exclusively non-male offspring. Interestingly, hermaphrodites emerge in response to specific social cues sensed by the maternal generation. These results can be attributed to unusual genetic phenomena, including non-Mendelian inheritance, chromatin diminution, inverted meiosis, and the occurrence of transgression. Our study not only unravels the complexities of sex determination in Auanema nematodes but also contributes to a broader understanding of genetic and evolutionary dynamics in developmental mechanisms.   Reference: DC.Shakes, et.al., Nature commun. 2 (1), 157 (2011) J. Chaudhuri, et.al., Scientific Reports 5 (1), 17676 (2015) N. Kanzaki, et.al., Scientific reports 7 (1), 11135 (2017) S. Tandonnet, et.al.,Curr. Biol., 28, 93-99 (2018) T. Al-Yazeedi, et.al., Genetics, 222, iyae159 (2022) T. Al-Yazeedi, et.al., Genetics, 227, iyae032 (2024) poster(PDF)  Contact 生命科学研究科　発生ダイナミクス分野 Grad. Sch. of Life Sciences, Developmental Dynamics 杉本亜砂子 Asako Sugimoto E-mail：asako.sugimoto.d1(at)tohoku.ac.jp

https://www.lifesci.tohoku.ac.jp/date/seminar/detail---id-47384.html 2024-07-12T11:30:00+09:00

Information As members of society, we interact with diverse individuals in various environments, accumulating a broad spectrum of experiences. The memories we form through these interactions shape our individuality and are crucial for effective communication. This symposium will bring together researchers from both within and outside the country who study memory, stress, social behavior, and the neural circuits underlying these brain functions. Our goal is to deepen our understanding of social memory, the foundation of communication.   Date Thursday, September 5, 2024 – Friday, September 6, 2024   Venue September 5, 2024  Sendai Ryokusaikan Visitor Center [Access] September 6, 2024  Sakura Hall, Katahira Campus, Tohoku University [Access]   Speakers (in order of appearance) September 5, 2024 Menno Witter (Norwegian University of Science and Technology) * Teruhiro Okuyama (The University of Tokyo) Tomomi Shimogori (RIKEN) Yoko Yazaki–Sugiyama (Okinawa Institute of Science and Technology) Thomas McHugh (RIKEN) Takuya Sasaki(Tohoku University) Vannesa van Ast (University of Amsterdam) September 6, 2024 Kaoru Inokuchi (University of Toyama) * Shinya Ohara (Tohoku University) Nobuyoshi Matsumoto (The University of Tokyo) Gen–ichi Tasaka(RIKEN) Shusaku Uchida(Nagoya City University) Hidenori Aizawa (Hiroshima University) Takuya Osakada (New York University） Aki Takahashi (University of Tsukuba) Hideaki Takeuchi (Tohoku University) *Keynote speakers   Registration (pre–registration required) Registration fee: 3,000 yen for students, and 5,000 yen for post–doc researchers and faculty members. This will cover the foods and drinks for the social gathering on September 5 and the lunch during the poster session on September 6.   Registration deadline: Thursday, August 8, 2024 Registration Form     Organizers Menno Witter (Norwegian University of Science and Technology)   Hideaki Takeuchi (Tohoku University)   Shinya Ohara (Tohoku University)     Hosted by Tohoku Forum for Creativity   Co–hosted by Neuro Global International Joint Graduate Program Graduate School of Life Science, Tohoku University Tohoku University Graduate School of Medicine Tohoku University Brain Science Center poster   Contact Email: office*snlabsendai.org (change * to @)

https://www.lifesci.tohoku.ac.jp/ 2024-07-12T11:00:00+09:00

Program Theme Human beings have a fundamental need to communicate, belong to society, and achieve self–actualization through social interactions. Isolation can lead to disorders like depression and adjustment disorder. The rapid diversification of values and lifestyles has made many people societal minorities, increasing difficulties in living, working, or learning. This program aims to foster interdisciplinary collaboration among neuroscience, informatics, and robotics researchers. It seeks to understand the mind and develop new communication aids to help people connect. The program will significantly impact society by promoting social inclusion and diversity, and scientifically, it will benefit each field by integrating complementary technologies to study and interact with the human mind.   Events Social Memory: Neural Basis of Communication, Part 1 (September 5, 2024 – September 6, 2024)   Reward, Motivation, and Beyond: Neural Basis of Communication, Part 2 (October 14, 2024)   Towards the Future of Communication: Creating an Inclusive World with Neuro/Bioscience and Engineering Technologies (March 26, 2025 – March 28, 2025)   Organizers Ken–Ichiro Tsutsui (Professor, Graduate School of Life Sciences, Tohoku University)   Noriko Osumi (Professor, Tohoku University Graduate School of Medicine)   Hosted by Tohoku Forum for Creativity   Co–hosted by Neuro Global International Joint Graduate Program Graduate School of Life Sciences, Tohoku University Tohoku University Graduate School of Medicine Tohoku University Brain Science Center Moonshot Goal 9 National Research Program for Neurological Disorders and Mental Health Multidisciplinary Frontier Brain and Neuroscience Discoveries   Poster(PDF)   Link Tohoku Forum for Creativity

https://www.lifesci.tohoku.ac.jp/ 2024-06-20T16:00:00+09:00

【開催日時・Date】 2024.7.11(Thu) 16:00～17:30   【講師・Speaker】 太⽥緑博⼠(Dr. Midori Ota) 沖縄科学技術⼤学院⼤学/ 東北⼤学助教（クロスアポイントメント） Okinawa Institute of Science and Technology   【会場・Venue】ハイブリッド開催（Hybrid） 片平・生命科学プロジェクト研究棟講義室AB Life Sciences Project Research Laboratory, Lecture hall   【事前登録・Pre-registration】 Zoom link https://zoom.us/meeting/register/tJApdOiuqTItE91gggubj7O_rpVCM-HV06cy   【使用言語・Languate】 English   【題目・Title】 Mechanism of γ-tubulin complex docking on mitotic centrosomes   Poster（PDF）   Contact 生命科学研究科　発生ダイナミクス分野 Grad. Sch. of Life Sciences, Developmental Dynamics 杉本亜砂子 Asako Sugimoto E-mail：asako.sugimoto.d1(at)tohoku.ac.jp TEL：022-217-6194

https://www.lifesci.tohoku.ac.jp/date/seminar/detail---id-47378.html 2024-05-13T00:00:00+09:00

Course outline 2024 has been updated. Please see below.           Graduate school of life sciences, Tohoku University 2024 (12.9MB) (Written in both Japanese & English)    

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/ 2024-04-23T13:00:00+09:00

https://www.oist.jp/news-center/news/2024/4/23/biodiversity-invertebrates-key-planetary-health 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/