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14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de
Depression is among the leading causes of disability and disease burden. Recent studies point to an involvement of altered serotonin1A receptor (5-HT1AR) -mediated adult neurogenesis and gliogenesis in depression. However, the exact underlying mechanisms remain unclear, mainly due to the diverse external and internal influences on neurogenesis and the complexity of the serotonergic system with its various receptors and their locations. Mice with permanent overexpression of postsynaptic 5-HT1ARs (OE mice) represent a unique tool for investigating the involvement of postsynaptic 5-HT1ARs in this context. Previous studies demonstrated correct 5-HT1A receptor coupling and functioning in OE mice. Here, we examined proliferation and survival of newborn cells in the adult dentate gyrus (DG) of OE mice in comparison to wild-type (WT) mice. Ten weeks old OE and WT mice were treated with bromodeoxyuridine (BrdU) to label newly generated cells. (50 mg/kg intraperitoneally on three consecutive days). Animals were killed either one day (proliferation) or 21 days (survival) after the last injection. For labelling of newborn cells, immunohistochemistry for BrdU (1:500) followed by the peroxidase method was performed. Proliferation as well as survival in the adult DG of new born cells in the dentate gyrus of OE mice was significantly increased. According to previously observed sex differences, a further analysis revealed only significant increases in the number of newly generated cells in the female but not in the male subgroup. In line with the hypothesis of a proneurogenic effect of the postsynaptic 5-HT1AR, our studies seem to confirm a leading role of this receptor in adult hippocampal neurogenesis. Future behavioral and immunohistochemical studies are under way to identify the phenotype of newborn cells and the influence of 5-HT1AR stimulation on the found alterations.