Rab18 Negatively Regulates Dopamine to Induce Adult Neurogenesis and Maternal Behaviors in Postpartum Mice

• Main Authors: Huang, Po-Wen, 黃柏文
• Other Authors: Wang, Tsu-Wei
• Format: Others
• Language: en_US
• Online Access: http://ndltd.ncl.edu.tw/handle/5f82p6

碩士 === 國立臺灣師範大學 === 生命科學系 === 106 === There are two places in the mammalian brain with adult neurogenesis. In the subventricular zone (SVZ) of the lateral ventricles, neural stem cells produce neuroblasts, which migrate along the rostral migratory stream (RMS) to the olfactory bulb (OB) and differentiate into mature neurons. The function of adult OB neurogenesis is odor discrimination and maternal behaviors. Neural stem cells of the subgranular zone (SGZ) in the dentate gyrus (DG) generate progenitor cells, which give rise to neurons in the DG of the hippocampus. The function of adult DG neurogenesis is anti-depression and hippocampal-dependent learning and memory. Rab18 is a member of Rab proteins, which belong to Ras-related superfamily of small GTPase. Previously, we find that Rab18 homozygous mutation mice (Rab18-/-) have defective adult neurogenesis and impaired maternal behaviors. In addition, we also discover that Rab18 negatively regulates dopamine secretion and positively regulates prolactin concentration in postpartum female mice. Therefore, we hypothesize that Rab18 regulates adult neurogenesis and maternal behaviors through inhibiting dopamine and increasing prolactin. To test it, Rab18-/- virgin female mice were treated with dopamine D2 receptor (D2Rs) antagonist haloperidol (HAL) and OB/DG neurogenesis was examined. We found that proliferating cells and neuroblasts in the SVZ were rescued when Rab18-/- virgin female mice were injected with HAL. Furthermore, proliferating cells and neuroblasts in the SGZ and neurogenesis in the DG were rescued in Rab18-/- virgin mice with HAL injection. In conclusion, Rab18 regulates proliferating cells and neuroblasts in the SVZ by inhibition of dopamine in virgin mice. Moreover, Rab18 regulates proliferating cell, neuroblast and neuron numbers in the SGZ/DG by inhibition of dopamine in virgin mice. In postpartum mice, Rab18 was required for neural stem cells in the SVZ and dopamine inhibited adult AOB neurogenesis. Furthermore, Rab18 regulated adult DG neurogenesis, the maintenance of neural stem cells in the SGZ, proliferating cells in the SVZ and SGZ and the production of neuroblasts in the SVZ through inhibition of dopamine in postpartum mice. In addition, we found that Rab18 might regulate maternal behaviors through inhibition of dopamine and it was required for odor discrimination, but not through inhibition of dopamine in postpartum mice. In the future, we will continue to study how Rab18 regulates maternal behaviors and odor discrimination in postpartum mice.