Depression is a serious and worldwide neuropsychiatric disesase, and developing novel antidepressant targets beyond the monoaminergic systems is now popular and necessary. Bone morphogenetic protein (BMP) signals modulate numerous developmental, physiological, and homeostatic processes. The functions of BMPs are also regulated by secreted extracellular antagonists such as chordin and noggin. Chordin has abundant expression in adult brain, and may play critical role in the central nervous system. In this study, the chronic social defeat stress (CSDS) model of depression, various behavioral tests, western blotting, quantitative real-time reverse transcription PCR, immunohistochemistry, recombinant mouse chordin protein and AAV-Chordin-EGFP were together used to explore the role of chordin in the pathogenesis of depression. It was found that CSDS significantly decreased the expression of chordin in the hippocampus but not other related brain regions. Moreover, both pharmacological and genetic overexpression of hippocampal chordin fully protected against the CSDS-induced depressive-like effects in mice. Collectively, hippocampal chordin could be a novel antidepressant target, and this study further highlights the importance of the hippocampal BMP system in the pathophysiology of depression.

中文翻译：

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海马脊索蛋白的过度表达可防止小鼠慢性社交失败压力引起的抑郁样效应。

抑郁症是一种严重的全球性神经精神疾病，开发单胺能系统以外的新型抗抑郁药靶点现在很流行，也很有必要。骨形态发生蛋白 (BMP) 信号调节许多发育、生理和稳态过程。BMP 的功能也受分泌的细胞外拮抗剂如 chordin 和 noggin 的调节。Chordin 在成人大脑中有丰富的表达，可能在中枢神经系统中起关键作用。本研究将抑郁症的慢性社会失败压力（CSDS）模型、各种行为测试、蛋白质印迹、实时定量逆转录PCR、免疫组织化学、重组小鼠chordin蛋白和AAV-Chordin-EGFP共同探讨了其作用。 chodin 在抑郁症发病机制中的作用。结果发现，CSDS 显着降低了海马区 chordin 的表达，但不降低其他相关脑区的 chordin 表达。此外，海马脊索蛋白的药理学和遗传过表达完全保护小鼠免受 CSDS 诱导的抑郁样作用。总的来说，海马脊索蛋白可能是一个新的抗抑郁靶点，这项研究进一步强调了海马 BMP 系统在抑郁症病理生理学中的重要性。