Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Genetics and Molecular Biology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Neuron. 2020 Oct 28;108(2):349-366.e6. doi: 10.1016/j.neuron.2020.07.039. Epub 2020 Sep 1.
Neural stem cells (NSCs) in the dentate gyrus (DG) reside in a specialized local niche that supports their neurogenic proliferation to produce adult-born neurons throughout life. How local niche cells interact at the circuit level to ensure continuous neurogenesis from NSCs remains unknown. Here we report the role of endogenous neuropeptide cholecystokinin (CCK), released from dentate CCK interneurons, in regulating neurogenic niche cells and NSCs. Specifically, stimulating CCK release supports neurogenic proliferation of NSCs through a dominant astrocyte-mediated glutamatergic signaling cascade. In contrast, reducing dentate CCK induces reactive astrocytes, which correlates with decreased neurogenic proliferation of NSCs and upregulation of genes involved in immune processes. Our findings provide novel circuit-based information on how CCK acts on local astrocytes to regulate the key behavior of adult NSCs.
神经干细胞（NSCs）位于齿状回（DG）中的特定局部龛位，支持其神经发生性增殖，从而在整个生命周期中产生成年新生神经元。局部龛位细胞如何在回路水平上相互作用以确保 NSCs 的持续神经发生尚不清楚。在这里，我们报告了内源性神经肽胆囊收缩素（CCK）从齿状回 CCK 中间神经元释放，在调节神经发生龛位细胞和 NSCs 中的作用。具体来说，刺激 CCK 的释放通过占主导地位的星形胶质细胞介导的谷氨酸能信号级联反应来支持 NSCs 的神经发生性增殖。相比之下，减少齿状回 CCK 会诱导反应性星形胶质细胞，这与 NSCs 的神经发生性增殖减少以及与免疫过程相关的基因上调相关。我们的研究结果提供了关于 CCK 如何作用于局部星形胶质细胞以调节成年 NSCs 的关键行为的新的基于回路的信息。
