若手道場口演（Wakate Dojo）

Wakate Dojo Homeostatic Regulation 若手道場口演ホメオスタシス1

7月25日（木）10:00～10:20　第10会場（万代島ビル　6F　会議室） 1WD10bm2-1 単一細胞 RNA seq によるストレス応答性神経細胞の特性解析 Masato Tanuma（田沼将人）¹，Atsushi Kasai（笠井淳司）¹，Hiroyuki Okuno（奥野浩行）²，Kosei Yamaura（山浦港生）¹，Misaki Niu（丹生光咲）¹，Kaoru Seiriki（勢力薫）^1,3，Takanobu Nakazawa（中澤敬信）^1,4，Shun Yamaguchi（山口瞬）⁵，Hitoshi Hashimoto（橋本均）^1,6,7,8 ¹大阪大院薬神経薬理 ²鹿児島大院医歯生化学・分子生物 ³大阪大国際共創大学院学位プログラム推進機構 ⁴大阪大歯薬理 ⁵岐阜大院医神経統御・高次神経形態 ⁶大阪大院連合小児発達子どものこころ ⁷大阪大データビリティフロンティア機構バイオサイエンス部門 ⁸大阪大先導的学際研究機構超次元ライフイメージング研究部門 In order to address the mechanisms of stress response of the brain, it is important to characterize the molecular properties of each stress-responsive neuron and understand how they differ from non-responsive neurons. Recently, we performed whole brain imaging at a single cell resolution in Arc-dVenus reporter mice, which express destabilized Venus in activated neurons. In these mice exposed to a single stressor, dVenus signals were observed in a small brain region that strongly contributed to the classification of stressed and control brains. Focusing on this brain region, here we examined the gene expression profiles of excitatory neurons and compared stress responsive neurons with their neighbouring non-responsive neurons, using single-cell RNA sequencing (scRNA-seq). In Arc-dVenus mice, excitatory neurons were labeled with the red fluorescent protein tdTomato expressed under the CaMKII promoter using the AAV-PHP.eB vector. After the mice were subjected to single social defeat stress for 10 minutes, individual tdTomato-positive and dVenus-positive neurons were manually picked up from acute brain slices of the region and their gene expression profiles were compared by scRNA-seq. We identified several genes whose expression is induced by the stress and those that may potentially classify the stress-responsive neurons from the non-responsive neurons. This study contributes to the understanding of the molecular basis of acute stress response in the brain and may open the door for further specific analysis of stress responsive neurons.		7月25日（木）10:20～10:40　第10会場（万代島ビル　6F　会議室） 1WD10bm2-2 視床の灰白質体積に対するFK506結合タンパク質の一塩基多型と母親の受容性の交互作用効果 Izumi Matsudaira（松平泉）¹，Kentaro Oba（大場健太郎）²，Hikaru Takeuchi（竹内光）²，Atsushi Sekiguchi（関口敦）³，Hiroaki Tomita（富田博秋）⁴，Ryuta Kawashima（川島隆太）²，Yasuyuki Taki（瀧靖之）² ¹東北大院医 ²東北大加齢研 ³国立精神・神経セ ⁴東北大院精神 Investigating the effect of gene-environment interactions (G × E) on brain structure is crucial to elucidate putative mechanisms associated with individual differences in the risk of psychiatric disorders. rs1360780 (C/T) is a functional single-nucleotide polymorphism (SNP) in the FK506 binding protein 51 (FKBP5) gene, which regulates the hypothalamic-pituitary adrenal axis (HPA axis) stress response. The minor T allele is regarded as vulnerable to stress due to the overproduction of FKBP5 and dysregulation of the HPA axis. The interactive effect between childhood maltreatment and the rs1360780 genotype on brain structure has been previously reported. However, it is unclear how this SNP modulates the association between non-adverse environments and brain structure. In this study, we examined the interactive effect of the rs1360780 genotype and maternal acceptance on regional gray matter volume (rGMVs) in 202 Japanese children using voxel-based morphometry. Based on multiple regression analysis, we found a significant positive association between maternal acceptance and rGMVs in the left thalamus of T allele carriers, but a significant negative association in C homozygotes. Post-hoc analysis revealed that T allele carriers had reduced thalamic rGMVs relative to C homozygotes at or below the 70th percentiles of maternal acceptance. Thus, our investigation determined that the effect of maternal acceptance levels on brain development is different depending on the rs1360780 genotype. Importantly, we found that the difference in brain structure between T allele carriers and C homozygotes exists even with low to moderate levels of maternal acceptance, which is not equivalent to maltreatment. The present study has contributed to enhance G × E research by emphasizing the necessity to investigate the role of non-adverse environmental factors.

7月25日（木）10:40～11:00　第10会場（万代島ビル　6F　会議室） 1WD10bm2-3 Role of Tob in the brain: An insight into stress-responsiveness function Mohieldin Magdy Mahmoud Youssef（Youssef Mohieldin Magdy Mahmoud）¹，Yuji Kiyama（Kiyama Yuji）²，Hiroaki Hamada（Hamada Hiroaki）³，Kristopher Montrose（Montrose Kristopher）¹，Patrick Stoney（Stoney Patrick）¹，Toru Suzuki（Suzuki Toru）⁵，Toshiya Manabe（Manabe Toshiya）⁴，Tadashi Yamamoto（Yamamoto Tadashi）¹ ¹Cell Signal Unit, Okinawa Institute of Science and Technology (OIST), Japan ²Laboratory of Biochemistry and Molecular Biology, Graduate school of medical and dental sciences, Kagoshima University, Japan ³Neural Computation Unit, Okinawa Institute of Science and Technology (OIST), Japan ⁴Institute of Medical Science, University of Tokyo, Division of Neuronal Network, Tokyo, Japan. ⁵Laboratory of immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan During our daily life, we face stressful events to which our body generates responses and memories of these events are stored in order to cope with their future occurrence. Transducer of ErbB2 (Tob), a member of the Tob/BTG anti-proliferative family proteins, has been implicated in cell proliferation, differentiation and the DNA damage response. In the brain, there are reports suggesting that Tob regulates complex behavioral processes such as learning and memory. Interestingly, Tob knockout mice exhibited increased brain weights in conjunction with structural Magnetic Resonance Imaging (MRI) which revealed increased volume compared to wild-type mice. Behavior analyses showed increased levels of anxiety and fear expression in Tob knockout mice. Additionally, fMRI analysis for the functional connectivity between different brain parts in Tob-knockout mice revealed altered hippocampal and pre-frontal cortex connectivity, which might predispose for impaired stress handling in mice. Since Tob protein has been shown to be responsive to different stress stimuli, restraint stress for mice subjects has been utilized as a stress model in this study. The neuronal molecular pathway for Tob in response to stress involving dynamic phosphorylation signaling events and changes in neurotransmitter's postsynaptic receptor levels will be elucidated. This study sets the stage for investigating the potential function of Tob in the brain in response to stress and involvement in neurological disorders.