公募シンポジウム

公募シンポジウム成体脳における新生ニューロンの機能と治療的応用

7月8日（土）　16:00-18:00　Room F 3SY⑨-1 睡眠中の新生ニューロンの記憶固定化における役割 Function of adult-born neurons for memory consolidation during sleep 坂口　昌徳^1,2 1. 筑波大学　国際統合睡眠医科学研究機構, 2. 筑波大学　医学医療系 Masanori Sakaguchi^1,2 1. WPI-IIIS, Univ Tsukuba, Tsukuba, Japan, 2. Facl Medicine, Univ Tsukuba "Patients with Post-traumatic stress disorder (PTSD) often experience nightmares, which may be a result of replaying traumatic experiences in the hippocampus¹. The hippocampus plays a crucial role in fear memory traces and adult-neurogenesis^2,3. Our recent research indicates that the activities of adult-born neurons (ABNs) during REM sleep are essential for fear memory consolidation⁴. We propose that reactivating the ABN ensemble activities that represent fear memory during REM sleep is necessary for its consolidation⁵. To investigate this hypothesis, we conducted a study of ABN ensemble activities during fear learning, consolidation, and retrieval. Our findings indicate a unique pattern of ABN ensemble activities during REM sleep, and we specifically targeted the reactivation of the ABN ensemble during this stage. Our results suggest that fear memory consolidation relies on the transient recruitment of ABNs that represent a specific context. References: 1.Skaggs Science 271:1870 1996. 2.Liu Nature 484:381 2012 3.Akers Stem cells 36:969 2018. 4.Kumar Neuron 107:552 2020 5.Koyanagi Neur Regen Res 14:20 2019"		7月8日（土）　16:00-18:00　Room F 3SY⑨-2 トラウマ記憶忘却を標的とするPTSDの治療方法の開発 Forgetting of fear memory as a therapeutic target for PTSD 喜田　聡東京大学大学院　農学生命科学研究科 Satoshi Kida Graduate School of Agriculture and Life Sciences, The University of Tokyo Fear memory processes are thought to be therapeutic targets for emotional disorders such as post-traumatic stress disorder (PTSD). A previous study has shown that increasing adult hippocampal neurogenesis enhances the forgetting of hippocampus-dependent memory. Therefore, we tried to examine the effects of neurogenesis enhancers on forgetting hippocampus-dependent fear memory to develop methods to improve PTSD. To do this, we have used memantine (MEM) and exercise as neurogenesis enhancers. MEM is a noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist and has been known to enable to increase in adult hippocampal neurogenesis. We showed that forgetting recent fear memory is promoted by treatment with memantine (MEM). More importantly, we found that enhancers of hippocampal neurogenesis (MEM and exercise) promote forgetting of even remote contextual fear memory, hippocampus-independent memory, only after long-term retrieval of fear memory. Furthermore, we suggested that remote fear memory returns to a hippocampus-dependent state after this long-term retrieval, thereby allowing enhancement of forgetting by increased hippocampal neurogenesis. Collectively, our findings raise the possibility that fear memory forgetting is a novel therapeutic target of PTSD and may contribute to the improvement of PTSD.

7月8日（土）　16:00-18:00　Room F 3SY⑨-3 Migration and maturation of new neurons in the post-stroke brain 金子　奈穂子同志社大学　大学院　脳科学研究科 Naoko Kaneko Div. of Neuronal Regen., Grad. Sch. of Brain Sci., Doshisha Univ., Kyoto, Japan After ischemic stroke, new neurons generating in the postnatal ventricular-subventricular zone (V-SVZ) migrate toward the infarct area, where they mature into neurons. We are studying the mechanisms of neuronal regeneration using a mouse model for ischemic stroke. We found that the fates of the V-SVZ-derived new neurons are altered depending on their positioning, and increased migration efficiency of the new neurons through the meshwork of reactive astrocytes along the blood vessels promotes neurological recovery after stroke. These results suggest that manipulating interaction of the new neurons with surrounding astrocytes is critical for their fate determination, which will be critical for successful neuronal regeneration in stem/progenitor cell-based therapies for brain injury.		7月8日（土）　16:00-18:00　Room F 3SY⑨-4 脳傷害部への新生ニューロンの移動促進による機能回復 Promotion of neuronal migration to the site of brain injury facilitates functional recovery 中嶋　智佳子¹, 大野　雄也¹, 澤田　雅人^1,2, 金子　奈穂子³, 澤本　和延^1,2 1. 名古屋市立大学大学院医学研究科脳神経科学研究所神経発達・再生医学分野, 2. 自然科学研究機構生理学研究所神経発達・再生機構研究部門, 3. 同志社大学大学院脳科学研究科神経再生機構部門 Chikako Nakajima¹, Yuya Ohno¹, Masato Sawada^1,2, Naoko Kaneko³, Kazunobu Sawamoto^1,2 1. Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 2. Division of Neural Development and Regeneration, National Institute for Physiological Sciences, 3. Laboratory of Neuronal Regeneration, Graduate School of Brain Science, Doshisha University Postnatal neuronal migration is an essential process of brain development in organisms, including human infants. Young neurons derived from neural stem cells in the ventricular-subventricular zone (V-SVZ) move from their birthplace to the site of integration under both physiological and pathological conditions. The pathological condition, such as brain injury, activates neurogenesis and promotes the neuronal migration towards lesion sites where neurons are lost. However, it is a challenge to achieve a sufficient supply of young neurons and regenerated functional neurons at distant injury sites and ultimately to achieve functional recovery. It is important to modify the ability of neurons to migrate and/or the microenvironment based on an understanding of the cell biological mechanisms of neuronal migration. To address this, we have focused on the function of the scaffold cells that guide neuronal migration. In this talk, we will present our recent results using a novel biomaterial that promotes neuronal migration in the injured adult and neonatal mouse brain by providing a concentrated source of functional molecules and defining the migration route. Application of the biomaterial achieved neuronal regeneration and functional recovery after brain injury, providing a novel therapeutic strategy.

7月8日（土）　16:00-18:00　Room F 3SY⑨-5 新生児脳がもつ脳の再生能力 Regenerative capacity of endogenous neural stem cells in the neonatal brain 神農　英雄^1,2, Lauren Rosko², Satoshi Yamashita², Artur Agaronyan³, Tu Tsang-Wei³, Yuka Imamura⁴, Kazue Hashimoto-Torii², Nobuyuki Ishibashi², Vittorio Gallo² 1. 名古屋市立大学大学院医学研究科　新生児・小児医学分野, 2. Center for Neuroscience Research, Children's National Hospital, 3. Molecular Imaging Laboratory, Dept. of Radiology, Howard Univ., 4. Dept. of Pharmacol. Biochem. and Molecular Biology, Pennsylvania State Univ. College of Medicine Hideo Jinnou^1,2, Lauren Rosko², Satoshi Yamashita², Artur Agaronyan³, Tu Tsang-Wei³, Yuka Imamura⁴, Kazue Hashimoto-Torii², Nobuyuki Ishibashi², Vittorio Gallo² 1. Dept. of Pediatrics and Neonatology, Nagoya City Univ., Nagoya, Japan, 2. Center for Neuroscience Research, Children's National Hospital, 3. Molecular Imaging Laboratory, Dept. of Radiology, Howard Univ., 4. Dept. of Pharmacol. Biochem. and Molecular Biology, Pennsylvania State Univ. College of Medicine Despite recent advancements in perinatal care, the incidence of neonatal brain injury has not decreased. No therapies are currently available to repair injured brain tissues. In the postnatal brain, neural stem cells (NSCs) reside in the subventricular zone (SVZ) to produce neuroblasts and oligodendrocyte precursor cells (OPCs). After brain injury in rodents, SVZ-derived neuroblasts and OPCs migrate toward the injured area to mature into neurons and oligodendrocytes. Notably, the neonatal brain has a high regenerative capacity, raising the possibility that the SVZ could be a source for endogenous neural regeneration after neonatal brain injury. However, the capacity of human NSCs in response to injury remains largely unknown. Considerable structural differences exist between the rodent and human brain, including the different size and development of gyrencephalic cortex and white matter, and the composition of the SVZ. On the other hand, the developing human brain contains the additional source of NSCs in the outer SVZ populated with outer radial glia. We recently analyzed human brain tissues and piglet brains, a powerful model to study human brains, and found the regenerative mechanism specific to the human neonate. Activating the regenerative capacity in the neonatal brain could lead to the development of novel therapeutic strategies for brain injury.