https://scholars.lib.ntu.edu.tw/handle/123456789/627359
標題: | Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control | 作者: | PEI-HSIN HUANG Yang, Tsung-Ying Yeh, Chia-Wei Huang, Sheng-Min Chang, Ho-Ching Hung, Yun-Fen Chu, Wen-Chia Cho, Kuan-Hung TZU-PIN LU PO-HSIU KUO LI-JEN LEE Kuo, Li-Wei Lien, Cheng-Chang Cheng, Hwai-Jong |
關鍵字: | TREATMENT-RESISTANT DEPRESSION; BCL-2 FAMILY; MITOCHONDRIAL DYSFUNCTION; ANXIETY; CONNECTIVITY; DISORDERS; NEUROGENESIS; EPIDEMIOLOGY; METAANALYSIS; UNDERLIES | 公開日期: | 26-九月-2022 | 出版社: | SPRINGERNATURE | 卷: | 12 | 期: | 1 | 來源出版物: | Translational psychiatry | 摘要: | Mood disorders are an important public health issue and recent advances in genomic studies have indicated that molecules involved in neurodevelopment are causally related to mood disorders. BLM-s (BCL-2-like molecule, small transcript isoform), a BH3-only proapoptotic BCL-2 family member, mediates apoptosis of postmitotic immature neurons during embryonic cortical development, but its role in the adult brain is unknown. To better understand the physiological role of Blm-s gene in vivo, we generated a Blm-s-knockout (Blm-s-/-) mouse. The Blm-s-/- mice breed normally and exhibit grossly normal development. However, global depletion of Blm-s is highly associated with depression- and anxiety-related behaviors in adult mutant mice with intact learning and memory capacity. Functional magnetic resonance imaging of adult Blm-s-/- mice reveals reduced connectivity mainly in the ventral dentate gyrus (vDG) of the hippocampus with no alteration in the dorsal DG connectivity and in total hippocampal volume. At the cellular level, BLM-s is expressed in DG granule cells (GCs), and Blm-s-/- mice show reduced dendritic complexity and decreased spine density in mature GCs. Electrophysiology study uncovers that mature vGCs in adult Blm-s-/- DG are intrinsically more excitable. Interestingly, certain genetic variants of the human Blm homologue gene (VPS50) are significantly associated with depression traits from publicly resourced UK Biobank data. Taken together, BLM-s is required for the hippocampal mood control function. Loss of BLM-s causes abnormality in the electrophysiology and morphology of GCs and a disrupted vDG neural network, which could underlie Blm-s-null-associated anxiety and depression. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627359 | ISSN: | 2158-3188 | DOI: | 10.1038/s41398-022-02184-6 |
顯示於: | 病理學科所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。