期刊
JOURNAL OF AFFECTIVE DISORDERS
卷 75, 期 1, 页码 59-64出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0165-0327(02)00044-7
关键词
astrocyte; fluoxetine; neurogenesis; S100; RAGE
Background: Since the early 1950s, various molecular mechanisms have been invoked to explain how antidepressants work. The most recent suggests that pharmacologically stimulated adult neurogenesis might be involved. Surprisingly, in the adult brain, an important source of new neurons and possibly mediators of neurogenesis appears to be glia, i.e., astrocytes. We have recently shown that protracted administration of the antidepressant fluoxetine to adult rats upregulated the astrocytic protein S100beta content and increased neurogenesis in the hippocampus. Methods: Rats were treated with fluoxetine for 21 days; before sacrifice bromodeoxyuridine (BrdU) was injected to label the proliferating cells. Immunofluorescence was used to identify proliferating BrdU-positive cells, and cells immunopositive for S100beta and its receptor receptor for advanced glycation end products (RAGE). Results: Typically, S100beta-positive cells were observed in the vicinity of BrdU-positive cells. On the other hand, we observed colocalization of RAGE receptors and BrdU immunoreactivities, suggesting that some proliferating cells express these receptors for S100beta. RAGE expression by neuronal cells or neuronal precursors and its activation by S100beta may promote their survival. Limitations: The anatomical localization of hippocampal S100beta, its receptor RAGE, and BrdU-positive cells that we describe in this study is only indicative of a putative role for glia in antidepressant-stimulated neurogenesis. Functional in vitro and in vivo studies are needed to directly investigate this role; quantitative assays and time-course studies are also warranted. Conclusion: We propose that a better understanding of glia functioning could establish its role as a target for novel antidepressant treatments. (C) 2002 Elsevier Science B.V. All rights reserved.
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