Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia.
Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department, 115419 Moscow, Russia.
Int J Mol Sci. 2022 Apr 12;23(8):4261. doi: 10.3390/ijms23084261.
The dentate gyrus (DG), an important part of the hippocampus, plays a significant role in learning, memory, and emotional behavior. Factors potentially influencing normal development of neurons and glial cells in the DG during its maturation can exert long-lasting effects on brain functions. Early life stress may modify maturation of the DG and induce lifelong alterations in its structure and functioning, underlying brain pathologies in adults. In this paper, maturation of neurons and glial cells (microglia and astrocytes) and the effects of early life events on maturation processes in the DG have been comprehensively reviewed. Early postnatal interventions affecting the DG eventually result in an altered number of granule neurons in the DG, ectopic location of neurons and changes in adult neurogenesis. Adverse events in early life provoke proinflammatory changes in hippocampal glia at cellular and molecular levels immediately after stress exposure. Later, the cellular changes may disappear, though alterations in gene expression pattern persist. Additional stressful events later in life contribute to manifestation of glial changes and behavioral deficits. Alterations in the maturation of neuronal and glial cells induced by early life stress are interdependent and influence the development of neural nets, thus predisposing the brain to the development of cognitive and psychiatric disorders.
齿状回（DG）是海马的重要组成部分，在学习、记忆和情绪行为中起着重要作用。在其成熟过程中，可能影响 DG 中神经元和神经胶质细胞（小胶质细胞和星形胶质细胞）正常发育的因素会对大脑功能产生持久影响。早期生活应激可能会改变 DG 的成熟，并诱导其结构和功能的终身改变，从而导致成年人的脑病理学。本文全面综述了神经元和神经胶质细胞（小胶质细胞和星形胶质细胞）的成熟以及早期生活事件对 DG 成熟过程的影响。早期产后干预影响 DG，最终导致 DG 中的颗粒神经元数量改变、神经元异位和成年神经发生改变。生命早期的不良事件会导致海马神经胶质细胞在应激暴露后立即发生细胞和分子水平的促炎变化。之后，细胞变化可能消失，但基因表达模式的改变仍然存在。以后生活中的额外应激事件会导致神经胶质细胞的变化和行为缺陷的表现。早期生活应激引起的神经元和神经胶质细胞成熟的改变是相互依存的，并影响神经网络的发育，从而使大脑容易发生认知和精神障碍。
