METHODS: We used chronic social defeat stress (CSDS) to mimic depression in C57 mice to investigate the pathophysiological changes in the hippocampus associated with depression and assess the antidepressant effect of electroacupuncture (EA). Molecular, histological, and electron microscopic techniques were utilized to study intracellular stress responses, including the ER stress pathway reaction, mitochondrial damage, and structural and functional changes in MAMs in the hippocampus after CSDS. Proteomics technology was employed to explore protein-level changes in MAMs caused by CSDS.
RESULTS: CSDS caused mitochondrial dysfunction, ER stress, closer contact between ER and mitochondria, and enrichment of functional protein clusters at MAMs in hippocampus along with depressive-like behaviors. Also, EA showed beneficial effects on intracellular stress responses and depressive-like behaviors in CSDS mice.
CONCLUSIONS: The cellular specificity of MAMs related protein changes in CSDS mice was not explored.
CONCLUSIONS: In the hippocampus, ER stress and mitochondrial damage occur, along with enriched mitochondria-ER interactions and MAM-related protein enrichment, which may contribute to depression\'s pathophysiology. EA may improve depression by regulating intracellular stress responses.
方法:我们使用慢性社会失败应激(CSDS)模拟C57小鼠的抑郁症,以研究与抑郁症相关的海马的病理生理变化,并评估电针(EA)的抗抑郁作用。分子,组织学,和电子显微镜技术被用来研究细胞内应激反应,包括内质网应激途径反应,线粒体损伤,CSDS后海马MAMs的结构和功能变化。采用蛋白质组学技术探讨CSDS引起的MAMs蛋白水平变化。
结果:CSDS导致线粒体功能障碍,ER压力,内质网和线粒体之间更紧密的接触,海马MAMs功能蛋白簇的富集以及抑郁样行为。此外,EA对CSDS小鼠的细胞内应激反应和抑郁样行为显示出有益的作用。
结论:没有研究CSDS小鼠MAMs相关蛋白变化的细胞特异性。
结论:在海马中,ER应激和线粒体损伤发生,随着富集的线粒体-ER相互作用和MAM相关的蛋白质富集,这可能有助于抑郁症的病理生理学。EA可以通过调节细胞内应激反应来改善抑郁。