Latchney Sarah E, Ruiz Lopez Brayan R, Womble Paige D, Blandin Katherine J, Lugo Joaquin N
Department of Biology, St. Mary's College of Maryland, St. Mary's City, MD, United States.
Department of Psychology and Neuroscience, Baylor University, Waco, TX, United States.
Front Mol Neurosci. 2023 Dec 7;16:1308066. doi: 10.3389/fnmol.2023.1308066. eCollection 2023.
Adult neurogenesis is a persistent phenomenon in mammals that occurs in select brain structures in both healthy and diseased brains. The tumor suppressor gene, phosphatase and tensin homolog deleted on chromosome 10 () has previously been found to restrict the proliferation of neural stem/progenitor cells (NSPCs) . In this study, we aimed to provide a comprehensive picture of how conditional deletion of may regulate the genesis of adult NSPCs in the dentate gyrus of the hippocampus and the subventricular zone bordering the lateral ventricles. Using conventional markers and stereology, we quantified multiple stages of neurogenesis, including proliferating cells, immature neurons (neuroblasts), and apoptotic cells in several regions of the dentate gyrus, including the subgranular zone (SGZ), outer granule cell layer (oGCL), molecular layer, and hilus at 4 and 10 weeks of age. Our data demonstrate that conditional deletion of in mice produces successive increases in dentate gyrus proliferating cells and immature neuroblasts, which confirms the known negative roles has on cell proliferation and maturation. Specifically, we observe a significant increase in Ki67+ proliferating cells in the neurogenic SGZ at 4 weeks of age, but not 10 weeks of age. We also observe a delayed increase in neuroblasts at 10 weeks of age. However, our study expands on previous work by providing temporal, subregional, and neurogenesis-stage resolution. Specifically, we found that deletion initially increases cell proliferation in the neurogenic SGZ, but this increase spreads to non-neurogenic dentate gyrus areas, including the hilus, oGCL, and molecular layer, as mice age. We also observed region-specific increases in apoptotic cells in the dentate gyrus hilar region that paralleled the regional increases in Ki67+ cells. Our work is accordant with the literature showing that serves as a negative regulator of dentate gyrus neurogenesis but adds temporal and spatial components to the existing knowledge.
成年神经发生是哺乳动物中一种持续存在的现象，在健康和患病大脑的特定脑结构中均会发生。肿瘤抑制基因10号染色体上缺失的磷酸酶及张力蛋白同源物（PTEN）先前已被发现可限制神经干/祖细胞（NSPCs）的增殖。在本研究中，我们旨在全面了解条件性缺失PTEN如何调节海马齿状回和侧脑室旁室下区成年NSPCs的发生。我们使用传统标记和体视学方法，对4周龄和10周龄时齿状回多个区域（包括颗粒下区（SGZ）、外颗粒细胞层（oGCL）、分子层和齿状回门）的神经发生的多个阶段进行了量化，这些阶段包括增殖细胞、未成熟神经元（神经母细胞）和凋亡细胞。我们的数据表明，小鼠中PTEN的条件性缺失会使齿状回增殖细胞和未成熟神经母细胞相继增加，这证实了PTEN对细胞增殖和成熟已知的负性作用。具体而言，我们观察到4周龄时神经源性SGZ中Ki67 +增殖细胞显著增加，但10周龄时未观察到。我们还观察到10周龄时神经母细胞延迟增加。然而，我们的研究通过提供时间、亚区域和神经发生阶段分辨率扩展了先前的工作。具体而言，我们发现PTEN缺失最初会增加神经源性SGZ中的细胞增殖，但随着小鼠年龄增长，这种增加会扩散到非神经源性齿状回区域，包括齿状回门、oGCL和分子层。我们还观察到齿状回门区凋亡细胞的区域特异性增加，这与Ki67 +细胞的区域增加平行。我们的工作与文献一致，表明PTEN作为齿状回神经发生的负调节因子，但为现有知识增加了时间和空间成分。
