Neurogenesis, the process in which new neurons are generated, occurs throughout life in the mammalian hippocampus. Decreased adult hippocampal neurogenesis (AHN) is a common feature across psychiatric disorders, including schizophrenia, depression- and anxiety-related behaviours, and is highly regulated by environmental influences. Epidemiological studies have consistently implicated maternal immune activation (MIA) during neurodevelopment as a risk factor for psychiatric disorders in adulthood. The extent to which the reduction of hippocampal neurogenesis in adulthood may be driven by early life exposures, such as MIA, is however unclear. We therefore reviewed the literature for evidence of the involvement of MIA in disrupting AHN. Consistent with our hypothesis, data from both in vivo murine and in vitro human models of AHN provide evidence for key roles of specific cytokines induced by MIA in the foetal brain in disrupting hippocampal neural progenitor cell proliferation and differentiation early in development. The precise molecular mechanisms however remain unclear. Nonetheless, these data suggest a potential latent vulnerability mechanism, whereby MIA primes dysfunction in the unique hippocampal pool of neural stem/progenitor cells. This renders offspring potentially more susceptible to additional environmental exposures later in life, such as chronic stress, resulting in the unmasking of psychopathology. We highlight the need for studies to test this hypothesis using validated animal models of MIA, but also to test the relevance of such data for human pathology at a molecular basis through the use of patient-derived induced pluripotent stem cells (hiPSC) differentiated into hippocampal progenitor cells.

神经发生，即产生新神经元的过程，发生在哺乳动物海马体的整个生命周期中。成人海马神经发生（AHN）减少是精神疾病的一个共同特征，包括精神分裂症、抑郁和焦虑相关行为，并且受到环境影响的高度调节。流行病学研究一致表明，神经发育过程中的母体免疫激活（MIA）是成年期精神疾病的危险因素。然而，成年期海马神经发生的减少在多大程度上可能是由早期生活暴露（如 MIA）引起的，目前尚不清楚。因此，我们回顾了文献，寻找 MIA 参与扰乱 AHN 的证据。与我们的假设一致，AHN体内小鼠和体外人类模型的数据提供了 MIA 在胎儿大脑中诱导的特定细胞因子在破坏发育早期海马神经祖细胞增殖和分化中的关键作用的证据。然而，确切的分子机制仍不清楚。尽管如此，这些数据表明了潜在的潜在脆弱机制，即 MIA 引发了独特的海马神经干/祖细胞库的功能障碍。这使得后代在以后的生活中可能更容易受到额外的环境暴露，例如慢性压力，从而导致精神病理学的暴露。我们强调需要进行研究，使用经过验证的 MIA 动物模型来检验这一假设，同时还需要通过使用分化为海马的患者来源的诱导多能干细胞 (hiPSC)，在分子基础上测试这些数据与人类病理学的相关性。祖细胞。