LAUSR

Adult neurogenesis persists throughout life in the mammalian subventricular zone (SVZ)-olfactory bulb (OB) pathway and the hippocampal dentate gyrus (DG). Although the precise mechanism regulating adult neurogenesis remains unclear, accumulating evidence implicates that adult neurogenesis plays important roles in neuropsychiatric disorders and maternal behaviors. Rab18, a Ras-like small GTPase, is recently identified to negatively regulate the secretory pathway. From ENU-mutagenized mouse screening, a null mutant line of Rab18 was identified and postpartum Rab18 null female mice had higher rates of neonaticide and infanticide, suggesting that these mice had defects in maternal behaviors and might suffer from postpartum anxiety/depression (PPD). Since adult neurogenesis is required for maternal behaviors and anti-anxiety, we hypothesize that Rab18 may regulate maternal behaviors through mediating adult neurogenesis. We found that adult neurogenesis in the OB and DG was decreased in both virgin and postpartum Rab18 null mice. Moreover, progenitor cell numbers and cell proliferation in neural stem cell niches of Rab18 null female mice were also decreased. In addition, prolactin was not induced in postpartum Rab18 null mice. Since dopamine is a prolactin inhibitor, we also found that the midbrain dopamine level in Rab18 null female mice was increased. Finally, prolactin could rescue neurogenic defects in postpartum Rab18 null mice. This study suggests that Rab18 regulates adult neurogenesis through dopamine and prolactin.