2-B-P-004 〇山下 怜矢、石本 尚大、増尾 友佑、加藤 将夫 Reiya Yamashita, Takahiro Ishimoto, Yusuke Masuo, Yukio Kato 金沢大・院薬・分子薬物治療学 Fac. Pharm., Kanazawa Univ. Tropomyosin related kinase B (TrkB) is a neurotrophic factor receptor that plays an important role in neurogenesis, generating neurons from neural stem cells. A decline in hippocampal neurogenesis has been reported to be related to the pathology of various neurodegenerative diseases such as depression. Therefore, promoting TrkB-mediated neurogenesis may be a potential therapeutic target for these diseases. In this study, we investigated the effects of TrkB overexpression on neurogenesis and depression-like behavior in a mouse model exposed to chronic social defeat stress (CSDS). For such purpose, we used the blood-brain barrier-permeable adeno-associated virus serotype PHP.eB containing a gene of Flag-tagged mouse TrkB (AAV-mTrkB). In mice intravenously (i.v.) administered AAV-mTrkB, the area of hippocampal newborn neuron marker Dcx-positive cells was significantly higher than that in the control AAV-treated group, suggesting that AAV-mTrkB promotes neurogenesis. After CSDS exposure, stress-susceptible mice and stress-resilience mice were separated and injected with each AAV. In the forced swimming test, the immobility time in stress susceptible mice i.v. administrated AAV-mTrkB was significantly shorter than the control AAV-treated group, suggesting that AAV-mTrkB shows an antidepressant-like activity. Taken together, peripheral administration of AAV-mTrkB may promote neurogenesis and show antidepressant-like activity. Further analysis of its pharmacological effects is needed for treatment of neurodegenerative diseases.