4.5 Article

Subfield-specific effects of chronic mild unpredictable stress on hippocampal astrocytes

期刊

EUROPEAN JOURNAL OF NEUROSCIENCE
卷 54, 期 5, 页码 5730-5746

出版社

WILEY
DOI: 10.1111/ejn.15234

关键词

astrocyte; CA1; CA3; hilus; molecular layer; Mus musculus; Sholl analysis; stress

资金

  1. Department of Science and Technology, Government of India [DST/INSPIRE/04-I/2016/000002]
  2. Science and Engineering Research Board [ECR/2017/003240]
  3. CSIR-NET Junior and Senior Research Fellowship

向作者/读者索取更多资源

Major depressive disorder is a debilitating neuropsychiatric illness affecting over 20% of the global population. Recent research has shown that astrocytes play a significant role in the pathophysiology and potentially the pathogenesis of major depression. Chronic stress has differential effects on astrocyte subpopulations within the hippocampus.
Major depressive disorder (MDD) is a debilitating neuropsychiatric illness affecting over 20% of the population worldwide. Despite its prevalence, our understanding of its pathophysiology is severely limited, thus hampering the development of novel therapeutic strategies. Recent advances have clearly established astrocytes as major players in the pathophysiology, and plausibly pathogenesis, of major depression. In particular, astrocyte density in the hippocampus is severely diminished in MDD patients and correlates strongly with the disease outcome. Moreover, astrocyte densities from different subfields of the hippocampus show varying trends in terms of their correlation to the disease outcome. Given the central role that hippocampus plays in the pathophysiology of depression and in the action of antidepressant drugs, changes in hippocampal astrocyte density and physiology may have a significant effect on behavioral symptoms of MDD. In this study, we used chronic mild unpredictable stress (CMUS) in mice, which induces a depressive-like state, and examined its effects on astrocytes from different subfields of the hippocampus. We used SOX9 and S100 beta immunostaining to estimate the number of astrocytes per square millimeter from various hippocampal subfields. Furthermore, using confocal images of fluorescently labeled glial fibrillary acidic protein (GFAP)-immunopositive hippocampal astrocytes, we quantified various morphology-related parameters and performed Sholl analysis. We found that CMUS exerts differential effects on astrocyte cell numbers, ramification, cell radius, surface area, and process width of hippocampal astrocytes from different hippocampal subfields. Taken together, our study reveals that chronic stress does not uniformly affect all hippocampal astrocytes; but exerts its effects differentially on different astrocytic subpopulations within the hippocampus.

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