Kobe University · Graduate School of Medicine / Faculty of Medicine

Research keywordsPACAP signaling・PAC1 receptor・sleep regulation・circadian rhythm・Parkinson disease models・dendritic spine morphogenesis

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• Strategy for the development of small-molecule antidepressant targeting PAC1 receptor2024 · Japanese Pharmacological Society, 2024年07月, Folia Pharmacologica Japonica, 159(4) (4), 219 - 224
• Protective Role of Apelin in a Mouse Model of Post-Intensive Care Syndrome.Post-Intensive Care Syndrome (PICS) is a serious condition involving physical weakness, depression, and cognitive impairment that develop during or after an intensive care unit (ICU) stay, often resulting in long-term declines in quality of life. Patients with acute respiratory distress syndrome (ARDS) and severe COVID-19 are at particularly high risk, yet the molecular mechanisms underlying PICS remain poorly understood. Here, we identify impaired Apelin-APJ signaling as a potential contributor to PICS pathogenesis via disruption of inter-organ homeostasis. Using a mouse model combining acute lung injury and hindlimb immobilization, we observed PICS-like features including muscle atrophy, lung inflammation, and neurobehavioral abnormalities such as anxiety-like behavior and special working memory. Single-cell RNA sequencing in brain revealed upregulation of gene programs associated with Alzheimer disease, depression, and neuroinflammation, particularly in endothelial cells and microglia. Concurrently, Apelin-APJ signaling was downregulated in skeletal muscle. These changes were exacerbated in Apelin-deficient mice and attenuated by muscle-specific Apelin overexpression, which also reduced systemic IL-6 and restored circulating Apelin levels. In ARDS survivors with severe COVID-19, ICU-acquired weakness (ICU-AW) was associated with reduced plasma Apelin and elevated IL-6 levels. Transcriptomic profiling of peripheral blood mononuclear cells from ICU-AW patients showed gene expression signatures linked to depression and neurodegeneration, mirroring murine findings. These data suggest that impaired Apelin-APJ signaling may play a role in PICS pathophysiology. While skeletal muscle appears to contribute to systemic Apelin levels, further studies are needed to clarify tissue-specific roles. Modulating this pathway could offer a therapeutic strategy to mitigate long-term outcomes in ICU survivors.
• Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice.Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide, implicated in emotional stress responses and anxiety-related disorders. Here, we examined whether our recently developed small-molecule non-peptide PACAP receptor antagonists could ameliorate anxiety-like behaviors induced by acute restraint stress in mice. The antagonists PA-9 and its derivative PA-915 improved anxiety-like behaviors in mice subjected to restraint stress. An anxiolytic effect was observed with single acute dose, suggesting their fast-acting properties. PA-915 demonstrated a statistically significant anxiolytic effect whereas fluoxetine did not. These results indicate the potential of PAC1 antagonists as a novel treatment for anxiety.
• Knockdown of the mitochondria-localized protein p13 protects against experimental parkinsonism.Mitochondrial dysfunction in the nigrostriatal dopaminergic system is a critical hallmark of Parkinson's disease (PD). Mitochondrial toxins produce cellular and behavioural dysfunctions resembling those in patients with PD Causative gene products for familial PD play important roles in mitochondrial function. Therefore, targeting proteins that regulate mitochondrial integrity could provide convincing strategies for PD therapeutics. We have recently identified a novel 13-kDa protein (p13) that may be involved in mitochondrial oxidative phosphorylation. In the current study, we examine the mitochondrial function of p13 and its involvement in PD pathogenesis using mitochondrial toxin-induced PD models. We show that p13 overexpression induces mitochondrial dysfunction and apoptosis. p13 knockdown attenuates toxin-induced mitochondrial dysfunction and apoptosis in dopaminergic SH-SY5Y cells via the regulation of complex I. Importantly, we generate p13-deficient mice using the CRISPR/Cas9 system and observe that heterozygous p13 knockout prevents toxin-induced motor deficits and the loss of dopaminergic neurons in the substantia nigra. Taken together, our results suggest that manipulating p13 expression may be a promising avenue for therapeutic intervention in PD.

• ミクロ・マクロスケールの蛍光ライブイメージング解析による幻覚の神経基盤の解明 新谷 勇介 日本学術振興会, 科学研究費助成事業, 特別研究員奨励費, 神戸大学, 2026年04月01日 - 2029年03月31日2026 · KUID parsed section
• 幻覚の責任領野の同定 新谷勇介 公益財団法人 先進医薬研究振興財団, 精神薬療分野 若手研究者助成金, 2025年12月 - 2026年11月2025 · KUID parsed section
• マルチモーダルVR装置を用いた幻覚の神経基盤に関する薬理学研究 新谷 勇介 日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 2024年04月 - 2027年03月2024 · KUID parsed section
• 大脳皮質マクロイメージング法を用いたうつ病の病態と治療機構に関する検討 日本学術振興会, 研究活動スタート支援, 2023年10月 - 2025年03月, 研究代表者2023 · KUID parsed section

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