理事会企画シンポジウム

理事会企画シンポジウム

2021/9/30　17:00～19:00　ZOOM A会場 PS1-1 胎生期脳で神経回路が作られる機序と成体脳で壊れた神経回路を治す方法 How to form neural circuit in developing brain and how to repair injured adult brain ^○竹居光太郎横浜市立大学大学院生命医科学研究科生体機能医科学 ^○Kohtaro Takei Dept. of Medical Life Science, Yokohama City University Graduate School of Medical Life Science As an introduction to the audience from high school, I will briefly explain how neural circuit is formed in developing brain. The process of neural circuit formation is mainly consisted of five steps such as neurogenesis, neutritogenesis, neurite outgrowth, axon guidance and synapse formation. Among their processes, I will show molecular basis of neurite outgrowth and axon guidance. How axon is extended and how axon is regulated by surrounding brain environment to find and reach to the target neuron. Then, I will move on to the next topic of how injured adult brain is possibly repaired. Brain injury, such as stroke and spinal cord injury results in severe sensory and motor deficits due to the poor regenerative capacity of the adult central nervous system (CNS). Poor neuronal regeneration is primarily caused by a large amount of axonal growth inhibitors expressed in a damaged CNS. The main molecule mediating axonal growth inhibitors is Nogo receptor-1 (NgR1). Lateral olfactory tract usher substance (LOTUS), identified by our research group, completely antagonizes NgR1 function, thereby promoting neuronal regeneration and functional recovery after injury. Therefore, I will introduce some studies on neuronal repair by using LOTUS function, as an example of strategy of induction of neural regeneration. I hope that my introductive talk will be some help to understand the background of neural development and regeneration.		2021/9/30　17:00～19:00　ZOOM A会場 PS1-2 ライブイメージングで解くニューロン遊走における核輸送の制御機構 Live-imaging of cytoskeletal control of nuclear transport in migrating neurons ^○見学美根子京都大学高等研究院iCeMS ^○Mineko Kengaku KUIAS-iCeMS, Kyoto University During brain development, neurons are born in the germinal zone and migrate orderly to form the ramified cortex. Delivery of the nucleus, the largest and stiffest cargo, presents the biggest physical challenge for migrating neurons to pass through the narrow interstitial space between other cells and extracellular matrices. Intensive studies have revealed that microtubules, actin and their associated motors, dynein and myosin, drive nuclear transport in neurons. However, where and how these cytoskeletal forces are converted to actual nuclear behaviors remain unclear. A major effort of my lab has been devoted to live-imaging of cytoskeletal dynamics during neuronal migration, using the cerebellar granule cell as a model. Unlike the prevailing view of dynein-driven constant forward movement, we found that both dynein and kinesin exert force on small points of the nuclear envelope and drive stochastic and inconsistent motions including rotation, elongation, and short-step bidirectional movements. In contrast to the point force of microtubule motors, the strong contractile force of actomyosin instead acts on a broad area of the nucleus. We observed that migrating neurons adopt differential actomyosin networks in the front and rear of the nucleus depending on the local extracellular microenvironments. These dynamic interplays of cytoskeletal forces are required for the nuclear delivery in the narrow paths in crowded neural tissue.

2021/9/30　17:00～19:00　ZOOM A会場 PS1-3 三子の魂百までを脳科学で読み解く Neuroscience of “What is bred in the bone will never come out of the flesh.” ^○下郡智美理化学研究所脳神経科学研究センター ^○Tomomi Shimogori RIKEN Center for Brain Science The development of the brain in early postnatal life is susceptible, complex, and crucial to proper function over a person's life. However, most of the effects of development appear after they have grown, therefore it is difficult to identify the problem in the adult brain. The main focus of our laboratory is trying to clarify how the brain changes along the time axis, especially how the developing brain forms neural circuits that match the environment. We have also realized that most work is conducted in rodents, primarily because there is an extensive range of genetic tools to investigate. However, the human brain is quite different from the mouse one. Our laboratory has also been tackling these difficulties by using the common marmoset (Callithrix jacchus) as a new animal model. We employ in situ hybridization (ISH) analysis to systematically analyze changes in gene expression throughout postnatal brain information to develop tools that allow us to reveal primate-specific brain structure, function, and connectivity.		2021/9/30　17:00～19:00　ZOOM A会場 PS1-4 シナプスを再生するためにシナプスを理解しよう If you cannot create, you do not understand synapses. ^○柚崎通介慶應義塾大学医学部・神経生理学 ^○Michisuke Yuzaki Department of Physiology, Keio University School of Medicine At least ~10¹⁴ synaptic connections are thought to be formed among ~10¹¹ neurons in the human brain. Abnormal synaptic connections likely contribute to various neuropsychiatric, neurodevelopmental and neurological disorders, such as schizophrenia, autism spectrum disorders and Alzheimer’s diseases. Thus, it is crucial to clarify the mechanisms by which vast numbers of connections are precisely established, maintained, and modified throughout life. Synaptic organizers, which mediate these processes, are classified into secreted factors, such as Wnt and FGF, and cell adhesion molecules, such as neurexins and neuroligins. Recently, a new class of synaptic organizers, secreted extracellular scaffolding proteins (ESPs), such as C1q family proteins, LGI1, neuronal pentraxins and glial thrombospondins, have been discovered. ESPs are secreted from neurons or glia and serve as scaffolds for pre- and postsynaptic membrane proteins at the synaptic cleft. Cbln1, a prototype of the C1q family synaptic organizers, is unique in that it is secreted from presynaptic neurons in an activity-dependent manner, and rapidly induces synapse formation in adult brain. Epileptic seizures repress Cbln1 mRNA in the ventral tegmental area, leading to impaired sociability in mice. In contrast, Cbln4 regulates inhibitory synapses between somatostatin-positive interneurons and pyramidal neurons in the cortex. In this talk, I would like to summarize what is known about synaptic organizers focusing on the C1q family of ESPs. I would also like to discuss how we could develop new therapeutic reagents for neurological disorders based on the findings of synaptic organizers. After all, as late Feynman said, what we cannot create, we do not understand.

2021/9/30　17:00～19:00　ZOOM A会場 PS1-5 老化によって衰える脳の修復力を回復させるメカニズム Age-dependent decline in remyelination capacity is mediated by apelin–APJ signaling ^○村松里衣子国立精神・神経医療研究センター神経研究所・神経薬理研究部 ^○Rieko Muramatsu Department of Molecular Pharmacology, National Institute of Neuroscience, National Age-related regeneration failure in the central nervous system can occur as a result of a decline in remyelination efficacy. The responsiveness of myelin-forming cells to signals for remyelination is affected by aging-related epigenetic modification; however, the molecular mechanism is not fully clarified. In the present study, we report that the apelin receptor (APJ) mediates remyelination efficiency with age. APJ expression in myelin-forming cells is correlated with age-associated changes in remyelination efficiency, and the activation of APJ promotes remyelination through the translocation of myelin regulatory factor. APJ signaling activation promoted remyelination in both aged mice with toxin-induced demyelination and mice with experimental autoimmune encephalomyelitis. In human cells, APJ activation enhanced the expression of remyelination markers. Impaired oligodendrocyte function in aged animals can be reversibly reactivated; thus, the results demonstrate that dysfunction of the apelin–APJ system mediates remyelination failure in aged animals, and that their myelinating function can be reactivated by APJ activation.