一般ポスター

一般ポスター精神疾患・発達障害

7月7日（金）　13:50-14:50　ポスター会場① 2P⑧-1 Sex difference of effects of fetal exposure to chlorpyriphos on cerebellar development. 貫野　頌悟豊橋技術科学大学　応用化学・生命工学課程 Shougo Kanno Toyohashi University of Technology, Toyohashi, Japan It has been reported that chemical exposure in utero increases the risk of developing Autism Spectrum Disorder (ASD) and some mental disorders. The cerebellum is an organ that controls motor functions, intentions, and emotions and has been shown to be a central site in the development of ASD. In the present study, we investigated the effect on cerebellar development and the sex difference of organophosphorus pesticides. Previously, we have observed the effects of pesticide exposure to chlorpyrifos (CPF), an organophosphate pesticide suspected to be a cause of ASD development. Traditionally ASD affects mostly males and boys more than females and girls; however, recent reports say females also have ASD frequently and severely. In this study, we investigated the sex difference of the effect of CPF exposure on cerebellar development. Pregnant rats on gestation day 16 (G16) were acutely administrated with 5 mg／kg of CPF. CPF exposure resulted in Purkinje cell (PC) irregularity and excess-folding of cerebellar lobule V and VI layers in both offspring; however, the number of PC was not decreased. Some female offspring showed much more folding than males, and the deviation of female folding was more significant than males. We suggest that male animals would be influenced equally, whereas females would show outlier abnormality randomly.		7月7日（金）　13:50-14:50　ポスター会場① 2P⑧-2 HDAC阻害剤による小脳発達の変化およびその空間異方性と性差 Alteration of cerebellar development induced with HDAC inhibitors; its spatial anisotropy and sex difference 田中　健吾¹, 松井　紗羅沙¹, 諌田　泰成², 吉田　祥子³ 1. 豊橋技術科学大学大学院　応用化学・生命工学, 2. 国立医薬品食品衛生研究所, 3. 豊橋技術科学大学　ダイバーシティ推進センター Kengo Tanaka¹, Sarasa Matsui¹, Yasunari Kanda², Sachiko Yoshida Yoshida³ 1. Dept Applied Chem & Life Sci, Toyohashi Univ of Technol, Toyohashi, Japan, 2. Div Pharmacology, National Institute of Health Sciences, Kawasaki, Japan, 3. Center for Diversity and Inclusion, Toyohashi Univ of Technol, Toyohashi, Japan Prenatal chemical exposure is one of the causes of developmental neurotoxicities, such as autism spectrum disorder (ASD) or mental disorders. We have observed changes in　the function and structure of the cerebellum and hippocampus in rats exposed to some chemicals during the fetal period using male animals; however, some reports said the　male/female ratio for those with moderate to severe intellectual disability is approximately 2:1ratio because females with ASD are more likely to camouflage. In the present study, we investigated the effect on cerebellar development with the exposure to HDAC inhibitors, valproate (VPA) 600 mg/kg p.o., butyrate (BA) 400 mg/kg p.o., trichostatin A (TSA) 2 mg/kg p.o. or actinonin (ACT) 5 mg/kg i.p., or herbicide, glyphosate (GLY) 1 mg/kg/day p.o., and the sex difference of their exposure. VPA or ACT induced excess folding between V and VI lobules much more in female offspring than male ones. On the deficit of Purkinje cells (PC), male offspring showed　significance against females, whereas, on the misarrangement of PC, females showed significance against males. Incomplete migration of granule cells to the inner granular layer was observed in each administrated offspring with spatial anisotropy along lobules. We suggest that neurodegeneration would befall males while misarrangement in females.

7月7日（金）　13:50-14:50　ポスター会場① 2P⑧-3 Exploring a novel molecular pathway underlies cerebellar development and autism spectrum disorder ダレウィッシュ　モハメド, 飯島　陽子, 飯島　崇利東海大学医学部医学科, 神奈川県, 日本 Mohamed Darwish, Yoko Iijima, Takatoshi Iijima Department of Molecular Life Science, School of Medicine,Tokai University, Kanagawa, Japan There is growing evidence that the cerebellum has been involved in neurodevelopmental disorders such as autism spectrum disorders (ASD). However, the molecular mechanism underlying cerebellar development/function and its implication in ASD are not fully understood. Here we report Neuron Derived Neurotropic Factor (NDNF) as a potential key molecule for cerebellar development and ASD. NDNF showed a strong, selective, and transient expression in Purkinje cells (PCs) during the early postnatal stages. The cerebella lacking NDNF showed morphological hallmarks of ASD such as reduced size and foliation defects with loss of the cerebellar fissures that separate lobules VI and VII. In addition, the climbing Fiber (CFs) terminals around the soma of PCs were abnormally retained suggesting that the synaptic elimination process between CFs and PC is disrupted. The GO analysis revealed that downregulated differentially expressed genes were significantly enriched in biological processes including anterograde trans-synaptic signaling, and synapse transmission. At the behavioral level, mice lacking NDNF showed behavioral abnormalities such as the absence of ultrasonic vocalizations and impairment in motor function. This work will uncover a novel molecular pathway that underlies cerebellar development and may hold therapeutical potential for treating ASD.		7月7日（金）　13:50-14:50　ポスター会場① 2P⑧-4 知的障害関連遺伝子CTBP1がマウス大脳皮質発達に果たす役割 Role of CTBP1 gene, a possible gene related to intellectual disability, in mouse cerebral cortex development 西條　琢真¹, 浜田　奈々子¹, 岡本　伸彦², 永田　浩一¹ 1. 愛知県医療療育総合センター　発達障害研究所　分子病態研究部, 2. 大阪母子医療センター　分子遺伝病研究部門 Takuma Nishijo¹, Nanako Hamada¹, Nobuhiko Okamoto², Koh-ichi Nagata¹ 1. Dept. of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Aichi, Japan, 2. Dept. of Molecular Medicine, Osaka Women's and Children's Hospital, Osaka, Japan The CTBP1 gene, encoding a transcriptional co-repressor, has been shown to be a possible gene related to intellectual disability and other neurodevelopmental disorders. However, pathophysiological mechanism caused by mutation of CTBP1 gene in the cortical development is not cleared. We here analyzed the role of CTBP1 in the development of mouse cerebral cortex using in utero electroporation and whole-cell patch clamp technique. Overexpression of CTBP1 mutants with the in utero electroporation technique in embryonic day 14 mice cortical layer II/III pyramidal neurons caused delay of neuronal migration, suppression of dendritic arborization and affected dendritic spine morphology in cortical layer II/III pyramidal neurons during brain development. On the other hand, axon elongation was not changed. Electrophysiological analyses using the whole-cell patch-clamp technique in postnatal day 12 to 19 mice cortical layer II/III pyramidal neurons showed that overexpression of CTBP1 mutants reduced firing rate and synaptic transmission. These results suggest that CTBP1 plays an essential role in corticogenesis especially neuronal migration, dendritic morphology and synaptic transmission. Its functional defects cause structural and functional impairment of cortical neurons, which is related to the pathophysiology of neurodevelopmental disorders.

7月7日（金）　13:50-14:50　ポスター会場① 2P⑧-5 マウス脳における小頭症/Seckel症候群責任遺伝子CEP152の発現解析 Expression analyses of Cep152, a responsible gene for Seckel syndrome/microcephaly, during mouse brain development 永田　浩一, 浜田　奈々子, 岩本　郁子愛知県医療療育総合センター発達障害研究所 Koh-ichi Nagata, Nanako Hamada, Ikuko Iwamoto Institute for Developmental Research, Aichi Developmental Disability Center Centrosomal protein 152 (Cep152) regulates centriole duplication as a molecular scaffold during the cell cycle. Its gene abnormalities are responsible for microcephaly and Seckel syndrome. In this study, we prepared an antibody against mouse Cep152, anti-Cep152, and performed expression analyses focusing on mouse brain development. Western blotting analyses revealed that Cep152 with a molecular mass of ~150 kDa was expressed strongly at E13 and then gradually decreased during the brain development process. In immunohistochemical analyses, Cep152 was enriched in the centrosome of neuronal progenitors at E14, whereas it was diffusely distributed mainly in the cytoplasm of cortical neurons at P18. In developing cerebellum at P7, Cep152 was localized at the centrosome in the external granular layer, where neurogenesis takes place. Notably, biochemical analysis revealed that Cep152 was also present in the post-synaptic density fraction. Subsequent immunofluorescent analyses showed co-localization of Cep152 with excitatory synaptic markers, PSD-95 and synaptophysin, but not with an inhibitory synaptic marker gephyrin in differentiated primary cultured hippocampal neurons. The obtained results suggest that Cep152 takes part not only in neurogenesis during corticogenesis but also in the regulation of synaptic function in differentiated neurons.