一般口演

一般口演1

2021/9/30　10:00～11:00　オンデマンド D会場 O1-1 人工シナプスコネクターと再生環境制御による脊髄損傷超回復モデルと解析 Hyper-recovery from inducing synapse connection and regulation of extracellular matrix. -Amelioration of spinal cord injury- ^○武内恒成¹, 笹倉寛之¹, 池野正史¹, 柚崎通介² 1.愛知医科大学医学部生物学細胞生物学, 2.Department of Physiology, School of Medicine, Keio University ^○Kosei Takeuchi¹, 寛之笹倉¹, 正史池野¹, 通介柚崎² 1.Department of Medical Cell Biology, Aichi Medical University, 2.Department of Physiology, School of Medicine, Keio University We attempt to establish the super-recovery mouse from spinal cord injury(SCI) by inducing artificial synapse connect and providing extra cellular matrix suitable for regeneration. This mouse will allow us to dissect the neural basis of adaptive circuits during recovery. We reported that synthetic synapse connector (CPTX) have outstanding property of restoring neurological function in spinal cord injury　(Suzuki et.al. Science. 2020). CPTX was developed as chimera-protein, which can bind pre-synaptic molecules (Nrx) and post-synaptic AMPAR. It should induce Nrx-CPTX-AMPAR transsynaptic bridges. CPTX-injected mice show the recovery from not only acute phase, but also sub-acute stages (1~2 weeks after SCI). These mice show the amelioration of SCI clearly. There were no direct effective therapeutic drug and methods has ever reported in these late stages of SCI. As the second strategy for amelioration of SCI, we regulate the microenvironment of extracellular matrix to induce axon regeneration. After the traumatic damages in central nervous system, fibroblasts and glia cells form the repulsive scar tissue (glial scar). Chondroitin sulfate (CS) play the most important and most effective regenerate-inhibitory molecules in this scar. We reported that CS-KO mice show dramatic post-injury recovery (Takeuchi et.al. Nature commun.). We developed and applied an antisense oligo (ASO) for knocking down of CS expression in a tissue specific manner. In addition, we were able to show the possibility of the effect of using it in combination with CPTX. Currently, we are optimizing the appropriate administration timing and dose. These mice show more dramatically cure from SCI (after 2~4weeks of SCI) than any reported method so far, and shown the possibility of super-recover mice.		2021/9/30　10:00～11:00　オンデマンド D会場 O1-2 アルツハイマー病モデルマウスの脳内において長距離の軸索再伸長を可能にする分子メカニズムの解明 Molecular mechanisms for long-distance axonal regeneration in the brain of Alzheimer’s disease model mouse ^○楊熙蒙, Chihiro Tohda 富山大学和漢医薬学総合研究所神経機能学領域 ^○Ximeng Yang, Chihiro Tohda Section of Neuromedical Science, Institute of Natural Medicine, University of Toyama Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by Aβ deposition and subsequent neural networks disruption in the brain. We previously found that diosgenin, a constituent of Dioscorea Rhizoma, recovered memory deficits in a mouse model of AD, 5XFAD. Besides, we firstly clarified that diosgenin administration promoted long-distance axonal regeneration in 5XFAD mice brains. Therefore, in the present study, we aimed to clarify molecular mechanisms for controlling accurate pathfinding of injured axons in AD brains. Axon-regenerated neurons (after diosgenin administration) in the neural circuits contributing memory formation; from the hippocampus to the prefrontal cortex, were selectively visualized by retrograde tracings. Naïve neurons and axon-regenerated neurons in the brain slices were separately captured by laser microdissection to serve DNA microarray. The gene (the name is closed; gene A), whose expression was the most elevated in axon-regenerated neurons, was overexpressed in hippocampal neurons of 5XFAD mice. As a result, overexpression of protein A significantly promoted axonal regeneration in the brain and recovered memory deficits in 5XFAD mice. Next, we focused on a protein A-interacting molecule, collagen I, that exists on extracellular space like axonal trails even after axons were degenerated by Aβ. When collagen I was coated on direction-specific extracellular space, protein A-overexpressed neurons extend axons more preferable to collagen I-coated direction. Our study clarified that protein A-collagen I interaction is key molecules for controlling accurate pathfinding of injured axons in AD brains. Protein A-driven axonal regeneration should be a novel therapeutic strategy for AD and other neurodegenerative diseases.

2021/9/30　10:00～11:00　オンデマンド D会場 O1-3 リン酸化プロテオミクスで同定した新規霊長類神経成長・再生マーカー Phosphorylation of GAP-43 T172 is a molecular marker representing the growing axons in a wide range of mammals including primates. ^○岡田正康¹, Asami Kawasaki³, Naoko Kaneko⁴, Hiroyuki Yamazaki⁵, Yohei Shinmyo⁶, Hiroshi Kawasaki⁶, Yonehiro Kanemura⁷, Kazunobu Sawamoto⁴, Manabu Natsumeda², Makoto Oishi², Yukihiko Fujii², Michihiro Igarashi³ 1.Department of Neurosurgery, Niigata University Medical and Dental Hospital, 2.Department of Neurosurgery, Brain research Institute, Niigata University, 3.Department of Neurochemistry and Molecular Cell Biology, School of Medicine and Graduate School of Medical/Dental Sciences, Niigata University, 4.Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 5.Faculty of Social Welfare, Gunma University of Health and Welfare, 6.Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, 7.Department of Biomedical Research and Innovation, Institute for Clinical Research, National Hospital Organization Osaka National Hospital ^○Masayasu Okada¹, Asami Kawasaki³, Naoko Kaneko⁴, Hiroyuki Yamazaki⁵, Yohei Shinmyo⁶, Hiroshi Kawasaki⁶, Yonehiro Kanemura⁷, Kazunobu Sawamoto⁴, Manabu Natsumeda², Makoto Oishi², Yukihiko Fujii², Michihiro Igarashi³ 1.Department of Neurosurgery, Niigata University Medical and Dental Hospital, 2.Department of Neurosurgery, Brain research Institute, Niigata University, 3.Department of Neurochemistry and Molecular Cell Biology, School of Medicine and Graduate School of Medical/Dental Sciences, Niigata University, 4.Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 5.Faculty of Social Welfare, Gunma University of Health and Welfare, 6.Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, 7.Department of Biomedical Research and Innovation, Institute for Clinical Research, National Hospital Organization Osaka National Hospital Human iPS cell (HiPSC)-derived neural progenitor cells are available to the basic studies on human neurons, but the identification of molecules involved in axonal growth or synaptogenesis, related to human events, is the issues to be solved. The growth cone is the dynamic structure located at the tip of developing axons, for synaptogenesis. To approach this above problem, we performed phosphoproteomics of the rodent growth cone and identified the phosphorylation of threonine (pT172) of growth-associated protein–43 kDa (GAP-43). Here, we show the localization of pT172, the identification method of phosphorylation-regulating kinase, and the result of examining the relationship between nerve growth and GAP-43 T172 in rodents, ferrets, and primates. We produced phospho-specific GAP-43 T172 antibodies (pT172) and obtained the following results: (1) The pT172 antibody is a marker for rodent nerve growth and axon regeneration; (2) The regulatory kinase for pT172 is c-jun N-terminal kinase (JNK), which is thought to be essential for brain development; (3) pT172 is also present in the fetal and the neonatal ferret brains; (4) pT172 is detected by phosphoproteomics of the neonatal common marmoset brains, and immunohistochemical studies confirm the presence of pT172 in in vivo growing axons; and (5) the differentiated neurons derived from hiPSC, have the pT172-positive growing axons and the growth cones. Taken together, pT172 is not simply only a marker for human axon growth, but a means of elucidating the mechanism of human axonal growth (M. Okada, M. Igarashi et al., Molecular Brain, 2021). In addition, we believe that our approach will be helpful to search for the molecules involved in human neuronal development.		2021/9/30　10:00～11:00　オンデマンド D会場 O1-4 軸索起始部の変化より明らかとなるASDモデルマウスの内側前頭前野の異常神経回路 Alteration of axon initial segment in the pyramidal neuron of the medial prefrontal cortex revealed abnormal neural circuitry in ASD model mice. ^○大谷嘉典, Yume Yamanaka, Masashi FUjitani 島根大学　医学部　解剖学講座（神経科学） ^○Yoshinori Otani, Yume Yamanaka, Masashi FUjitani Department of Anatomy and Neuroscience , Faculty of Medicine, Shimane University Autism spectrum disorder (ASD) is a developmental disorder involving impairments in communication, reciprocal social interaction and restricted repetitive behaviors or interests. Duplication of the human chromosome 15q11-13 region is the most frequently seen chromosomal abnormality and a risk factor for the development of ASD. The axon initial segment (AIS) is located at the proximal axon and has a high density of ion channels, which occurs action potential initiation. In addition, the AIS regulates the excitability of neurons by changing the structures which include length and position. Many studies reported abnormalities in AIS are risk factors that cause various neurological diseases. It already reported that amount of serotonin was abnormal in the brain of 15q11-13 duplication ASD mice. Therefore, we hypothesize whether neuronal circuit of dorsal raphe nucleus (DRN) where contain serotonin neuron are critical for phenotypes of 15q11-13 duplication mice. To address, we analyzed abnormal neural circuits related ASD by measuring the length of AIS by projection site specific method in 15q11-13 duplication and wild type mice. As our preliminary data, there was significant difference in the length of AIS of pyramidal neurons in the layer 5 of medial prefrontal cortex (mPFC) in 15q11-13 duplication mice. Therefore, we revealed abnormal neuronal circuit between mPFC and DRN in 15q11-13 duplication ASD mice by measuring the length of AIS.