Increased adult neurogenesis in mice with a permanent overexpression of the postsynaptic 5-HT receptor.

Depression is among the leading causes of disability and disease burden. Recent studies point to an involvement of altered serotonin receptor (5-HTR) -mediated adult neurogenesis in depression. However, the exact underlying mechanisms remain unclear, mainly due to the complexity of the serotonergic system with its various receptors and their locations. Mice with permanent overexpression of postsynaptic 5-HTRs (OE mice) represent a unique tool for investigating the involvement of postsynaptic 5-HTRs in this context. Correct 5-HTR coupling and functioning has been demonstrated earlier, indicating that more postsynaptic 5-HTRs can be activated in these mice. Initially we examined morphometric parameters of the dentate gyrus (DG) and the prefrontal cortex as they are involved in adult hippocampal neurogenesis and/or depression. The volume of the DG in OE mice was increased in comparison to wildtype controls. We therefore investigated parameters of adult neurogenesis by the bromodeoxyuridine method. Proliferation and survival of newborn cells in the DG of OE mice were significantly increased. Significant increases in survived neurons were only detected in the female but not in the male subgroup. Additional staining for early precursor cells (Sox2) and progenitor cells of the neuronal lineage (doublecortin) showed an increase in type-1/2a as well as in type-2b/3 cells in OE mice. Our study suggests a leading role of the postsynaptic 5-HTR in adult hippocampal neurogenesis and might open an important link to depression.