Rab18調節雄性小鼠的成年神經元新生和嗅覺行為
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2022
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在哺乳動物大腦中有兩個地方有成年神經元新生。在側腦室的腦室下區 (subventricular zone, SVZ)，神經幹細胞 (neural stem cell, NSC) 產生神經母細胞，並且沿著rostral migratory stream (RMS) 遷移到嗅球 (olfactory bulb, OB) 進而分化為成熟的神經元。齒狀回 (dentate gyrus, DG) 的顆粒下區 (subgranular zone, SGZ) 中的神經幹細胞產生祖細胞，進而在齒狀回中產生神經元。在SVZ-OB的成年神經元新生的功能是氣味的分辨和母性行為，而在齒狀回中的成年神經元新生功能為抗焦慮以及依賴海馬迴的學習和記憶。Rab18是Ras相關的小GTP水解酶家族中Rab蛋白的一員，其調控神經內分泌細胞多巴胺的釋放。先前研究發現，在出生後的SVZ中，Rab18能維持神經幹細胞的增殖。這裡，我們測試了在Rab18活化和不活化時期對神經幹細胞的影響。我們在NSC中轉染了Rab18 Q67L（有活性）或Rab18 S22N（無活性）。研究顯示，在Rab18不活化時，減少了神經幹細胞的增殖及神經幹細胞的自我更新，但並不影響其分化。這表示了Rab18對神經幹細胞的增殖及自我更新是必須的。除此之外，在體內試驗中，我們檢查了Rab18雄性小鼠的成年神經元新生。結果顯示，Rab18-/-雄性小鼠的神經幹細胞、增殖細胞和神經母細胞減少，在嗅球中新生的細胞和新生的神經元也減少，而對於神經元的分化並未減少，表示了Rab18對於成年神經元新生是必須的。此外，我們檢查了Rab18-/-雄性小鼠氣味分辨的能力和嗅覺敏感性。結果顯示Rab18-/-小鼠不能區分氣味且有較差的嗅覺能力，表示了Rab18可以調節雄性小鼠分辨氣味的能力以及嗅覺敏感性。所以，我們的結果顯示Rab18調節小鼠的成年神經元新生和嗅覺行為。
There are two places in the mammalian brain with adult neurogenesis. In the subventricular zone (SVZ) of the lateral ventricle, neural stem cells (NSCs) produce neuroblasts, which migrate along the rostral migratory stream (RMS) to the olfactory bulb (OB) and differentiate into mature neurons. NSCs 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 SVZ-OB neurogenesis is odor discrimination and maternal behaviors and the function of adult DG neurogenesis is anti-depression and hippocampal-dependent learning and memory. Rab18, a member of Ras-related small GTPase superfamily, regulates Ca2+-mediated exocytosis of dopamine in neuroendocrine cell lines. Previously, Rab18 has been shown to maintain the proliferation of NSCs in the postnatal SVZ. Here, we examined the proliferation and self-renewal of NSCs when Rab18 was active or inactive. We transfected Rab18 Q67L (active) or Rab18 S22N (inactive) in NSCs. This analysis revealed that the proliferation and self-renewal of NSCs was decreased when Rab18 was inactive, suggesting that Rab18 is required for the proliferation and self-renewal in NSCs. Moreover, we examined adult neurogenesis in adult Rab18-/- male mice. Neural stem cells, proliferation cells and neuroblasts in the SVZ of adult Rab18-/- mice were decreased. Newborn cells and newborn neurons, but not the neuronal differentiation in the OB of adult Rab18-/- mice were also decreased, suggesting that Rab18 is required for adult neurogenesis. Furthermore, we examined odor discrimination and olfactory sensitivity in Rab18-/- male mice. Rab18-/- mice could not discriminate odors and had poor olfactory detection ability, suggesting that Rab18 could regulate odor discrimination and olfactory sensitivity in male mice. Taken together, our results suggest that Rab18 regulates adult neurogenesis and olfactory behaviors in male mice.
There are two places in the mammalian brain with adult neurogenesis. In the subventricular zone (SVZ) of the lateral ventricle, neural stem cells (NSCs) produce neuroblasts, which migrate along the rostral migratory stream (RMS) to the olfactory bulb (OB) and differentiate into mature neurons. NSCs 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 SVZ-OB neurogenesis is odor discrimination and maternal behaviors and the function of adult DG neurogenesis is anti-depression and hippocampal-dependent learning and memory. Rab18, a member of Ras-related small GTPase superfamily, regulates Ca2+-mediated exocytosis of dopamine in neuroendocrine cell lines. Previously, Rab18 has been shown to maintain the proliferation of NSCs in the postnatal SVZ. Here, we examined the proliferation and self-renewal of NSCs when Rab18 was active or inactive. We transfected Rab18 Q67L (active) or Rab18 S22N (inactive) in NSCs. This analysis revealed that the proliferation and self-renewal of NSCs was decreased when Rab18 was inactive, suggesting that Rab18 is required for the proliferation and self-renewal in NSCs. Moreover, we examined adult neurogenesis in adult Rab18-/- male mice. Neural stem cells, proliferation cells and neuroblasts in the SVZ of adult Rab18-/- mice were decreased. Newborn cells and newborn neurons, but not the neuronal differentiation in the OB of adult Rab18-/- mice were also decreased, suggesting that Rab18 is required for adult neurogenesis. Furthermore, we examined odor discrimination and olfactory sensitivity in Rab18-/- male mice. Rab18-/- mice could not discriminate odors and had poor olfactory detection ability, suggesting that Rab18 could regulate odor discrimination and olfactory sensitivity in male mice. Taken together, our results suggest that Rab18 regulates adult neurogenesis and olfactory behaviors in male mice.
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Rab18, 成年神經元新生, 嗅覺行為, Rab18, adult neurogenesis, olfactory behavior