若手道場

若手道場神経発達障害

7月7日（金）　8:30-9:15　Room D 2W①-1 Rac-グアニンヌクレオチド交換因子Prex1の神経発達における生理機能 Prex1, a Rho-Guanine Nucleotide-Exchange Factor for Rac1/3, has an Essential Function in Neural Development 鳥居　紗帆¹, 西川　将司¹, 内山　由理², 後藤　直樹¹, 伊東　秀記³, 上田　浩⁴, 松本　直通², 永田　浩一^3,5, 木下　専¹ 1. 名古屋大学　理学研究科　理学専攻　生命理学領域　分子第一講座, 2. 横浜市立大学　医学部医学科　遺伝学　医学研究科医科学専攻, 3. 愛知県医療療育総合センター発達障害研究所, 4. 岐阜大学　工学系研究科, 5. 名古屋大学　医学系研究科 Saho Torii¹, Masashi Nishikawa¹, Yuri Uchiyama², Naoki Goto¹, Hidenori Ito³, Hiroshi Ueda⁴, Naomichi Matumoto², Koh-ichi Nagata^3,5, Makoto Kinoshita¹ 1. Department of Sciences, Nagoya University, 2. Graduate School of Medicine, Yokohama City University, 3. Institute for Developmental Research, Aichi Developmental Disability Center, 4. Faculty of Engineering, Gifu University, 5. Graduate School of Medicine, Nagoya University The Rac subfamily of small GTPases play critical roles in cellular morphogenesis by regulating signaling pathways and the actin cytoskeleton. Previous studies showed that Rac1/Rac3 are required for neural development, depending on their enzymatic activities and interactions with guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). A Rac GEF, termed the phosphatidyl inositol 3,4,5-trisphosphate (PIP3)-dependent Rac Exchanger 1 (PREX1), is expressed and activated during brain development, but the significance remains unknown. To address this, we acutely depleted PREX1 from developing mouse cerebral cortex. In utero electroporation-mediated RNAi at embryonic day 14 (E14) resulted in severely retarded migration and morphological anomalies of cortical neurons at postnatal day 0 (P0). Further, PREX1 depletion delayed dendritic arborization at P7, and reduced the number of dendritic spines at P14. Taken together, these results indicate a pleiotropic role for the PREX1-Rac1/3-actin axis in critical processes during corticogenesis; neuronal migration, neuritogenesis, and synaptogenesis.		7月7日（金）　8:30-9:15　Room D 2W①-2 Investigation of molecules responsible for controlling happiness, physical function, and cognitive function in humans 稲田　祐奈, 東田　千尋富山大学　和漢医薬学総合研究所　神経機能学領域 Yuna Inada, Chihiro Tohda Sec. of Neuromedical Science, Ins. of Natural Medicine, Univ. of Toyama Subjective well-being (SWB) is an important research topic being addressed from a variety of perspectives, including psychology, public health, and medicine. The fact that SWB is influenced by physical activity and cognitive activity, and vice versa SWB affects physical activity and cognitive activity, suggests that the locomotor system and cognitive function are closely related to mental health. However, the molecular basis of these interactions has not been clarified at all. This clinical study aimed to investigate what are related activities to SWB, and find molecules from the blood circulation, which are responsible for controlling SWB. Subjects were healthy elderly people aged 65 and over. Evaluation items were SWB, cognitive function (CF), motor function (MF) and daily activity (DA). Based on all points in those items, Structural Equation Modeling was conducted. The most fit model showed that CF, MF and DA are needed to explain SWB. Next, a comprehensive analysis of the molecules responsible for controlling high SWB in plasma revealed that protein X varied dependent on SWB level. A more detailed investigation is ongoing. There has been no molecular explanation of why physical activity, cognitive activity, and social activity affect SWB. The present study has the potential to answer the question and to provide a new perspective for health and longevity research.

7月7日（金）　8:30-9:15　Room D 2W①-3 深層学習を用いた発達障害モデルマウスの社会性行動障害に関わる機能的ネットワークの同定 Brain-wide IEG map and deep learning-based behavioral analysis reveal altered neural networks related to social deficits 植野　寛貴¹, 彌永　祐輔¹, 原　雄大^1,2, 大久保　仁¹, 中井　悠花¹, 勢力　薫¹, 山口　瞬^3,4, 吾郷　由希夫⁵, 田熊　一敞^6,7, 橋本　均^1,6,8,9,10, 笠井　淳司¹ 1. 大阪大　院薬　神経薬理, 2. 近畿大　薬　化学療法, 3. 岐阜大　院医　高次神経形態, 4. 岐阜大　生命の鎖統合研究センター, 5. 広島大　院医　細胞分子薬理, 6. 大阪大　院連合小児発達　子どものこころセンター, 7. 大阪大　院歯・薬理, 8. 大阪大　データビリティフロンティア機構, 9. 大阪大　先導的学際研究機構, 10. 大阪大　院医　分子医薬 Hiroki Ueno¹, Yusuke Iyanaga¹, Yuta Hara^1,2, Jin Ohkubo¹, Yuka Nakai¹, Kaoru Seiriki¹, Shun Yamaguchi^3,4, Yukio Ago⁵, Kazuhiro Takuma^6,7, Hitoshi Hashimoto^1,6,8,9,10, Atsushi Kasai¹ 1. Lab. Mol. Neuropharmacol., Grad. Sch. Pharmaceut. Sci., Osaka Univ., 2. Div. Chemotherapy, Fac. Pharm., Kindai Univ., 3. Dept. Morph. Neurosci., Grad. Sch. Med., Gifu Univ., 4. G-CHAIN, Gifu Univ., 5. Dept. Cell. Mol. Pharmacol., Grad. Sch. Biomed. Health Sci., Hiroshima Univ., 6. Unit. Grad. Sch. Child Dev., Osaka Univ., 7. Dept. Pharmacol., Grad. Sch. Dentistry, Osaka Univ., 8. Inst. Datability Sci., Osaka Univ., 9. Open Tarnsdiscip. Res. Initi., Osaka Univ., 10. Dep. Mol. Pharmaceut. Sci., Grad. Sch. Med., Osaka Univ. The pathogenesis of developmental disorders has been thought to congenital central neurological dysfunction; however, the underlying neural mechanisms remain unclear. Here, we analyzed the neural network associated with social deficits in a mouse model of developmental disorders using brain-wide immediate early gene (IEG) mapping in Arc-dVenus reporter mice and deep learning-based behavioral analysis. We found that the behaviors during social interaction test for 20 minutes in mice can be divided into 15 clusters using Uniform Manifold Approximation and Projection (UMAP) dimensionality reduction and watershed segmentation. Then, we found that the time of clusters that corresponds to social or nonsocial behavior was correlated with the number of Arc-dVenus-positive cells in each brain region. Using graph theoretical analysis, we found that the centralities of prefrontal and somatosensory cortices were decreased in valproic acid (VPA)- exposed mice. In addition, antiepileptics improved the decreased centralities of the functional network and the increased time of social behavior-related clusters in VPA-exposed mice. These results suggest that the centralities in the prefrontal and somatosensory cortices are therapeutic targets and neural markers for social deficits in developmental disorders.