Regulation of proliferation and AQP4 expression in adult neural precursor by GABAAR

GABAAR 对成人神经前体细胞增殖和 AQP4 表达的调节

• 批准号: 278467575
• 负责人: Dr. Francesca Ciccolini
• 金额: --
• 依托单位: Abteilung für Neurobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/278467575?language=en
• 关键词: Regulation; proliferation; AQP4; expression; adult

The lateral subependymal zone (SEZ) represents the main neurogenic niche in the adult murine brain. In this region the neurotransmitter gamma-aminobutyric acid (GABA) modulates the proliferation of both neural stem cells (NSCs) and their progeny. However, the outcome of this regulation on adult NSCs and the mechanisms involved are still debated. We have previously shown that in the neonatal SEZ GABAA receptor (GabaAr) activation induces osmotic swelling of NSCs by promoting Cl- influx as well as an increase in the expression of the Aquaporin (Aqp) 4 at the cell membrane. In the neonatal SEZ this leads to NSC activation and proliferation. We here propose to investigate whether GABA similarly affects adult NSCs and the contribution of the regulation of Aqp4 on the effect of the neurotransmitter on adult NSC proliferation. We will also examine the molecular mechanisms underlying the GABAergic regulation of Aqp4 expression. As we found that GabaAr function affects water exchange between the lateral ventricle and the germinal niche, the proposed project may provide new insights relevant not only to NSC proliferation but also to water exchange dynamics in the central nervous system.

外侧室管膜下区（SEZ）是成年小鼠脑内主要的神经原性小生境。在该区域中，神经递质γ-氨基丁酸（GABA）调节神经干细胞（NSC）及其后代的增殖。然而，这对成年神经干细胞的调节结果和所涉及的机制仍有争议。我们以前已经表明，在新生儿SEZ GABAA受体（GabaAr）激活诱导渗透性肿胀的神经干细胞通过促进Cl-流入以及增加水通道蛋白（Aqp）4在细胞膜上的表达。在新生儿SEZ中，这导致NSC活化和增殖。在这里，我们建议调查是否GABA同样影响成人神经干细胞和贡献的调节Aqp 4的神经递质对成人神经干细胞增殖的影响。我们还将研究GABA能调控Aqp 4表达的分子机制。由于我们发现GabaAr功能影响侧脑室和生殖器龛之间的水交换，因此该项目可能不仅与NSC增殖有关，而且与中枢神经系统中的水交换动力学有关。