Lyamtsev Alexander Sergeevich, Sentyabreva Alexandra Vladislavovna, Kosyreva Anna Mikhailovna
Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery, 117418 Moscow, Russia.
Research Institute of Molecular and Cellular Medicine, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russia.
Int J Mol Sci. 2025 Sep 22;26(18):9250. doi: 10.3390/ijms26189250.
Maternal Immune Activation (MIA) is a phenomenon of pathophysiological stimulation of the maternal immune system during gestation which potentially leads to functional and structural disturbances of fetal neurogenesis. It occurs due to the alteration of paracrine signals between the maternal organism and the developing nervous system of the fetus. Any disturbances in the brain at embryonic and early postnatal stages might compromise its natural developmental trajectory, which could potentially increase the risk of developing neuropsychiatric disorders, such as schizophrenia, autistic spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), major depressive and bipolar disorders, etc. Presumably, all these conditions could initiate the development of age-related cognitive impairment in late ontogenesis, including Alzheimer's disease (AD), Parkinson's disease (PD), and others. As the main immune cell population in the CNS, microglia both mediate its proper development and receive pathological stimuli from the maternal organism. This could lead to microglia premature activation and could become a part of the mechanisms of the fetal CNS development alterations. In this review, we discuss the role of prenatal activation of microglia in neuropsychiatric disorders and neurodegenerative disease development. We highlight approaches to modeling MIA, as well as sex differences in the morphological and functional state of microglia in the context of physiological conditions. There is a hypothesis discussed regarding the contribution of these distinctions to neuropsychiatric disorders and neurodegenerative disease incidence, prevalence, and progression in males and females.
母体免疫激活（MIA）是孕期母体免疫系统发生病理生理刺激的一种现象，它可能导致胎儿神经发生的功能和结构紊乱。它是由于母体生物体与胎儿发育中的神经系统之间旁分泌信号的改变而发生的。胚胎期和出生后早期大脑的任何紊乱都可能损害其正常的发育轨迹，这可能会增加患神经精神疾病的风险，如精神分裂症、自闭症谱系障碍（ASD）、注意力缺陷多动障碍（ADHD）、重度抑郁和双相情感障碍等。据推测，所有这些情况都可能引发个体发育后期与年龄相关的认知障碍的发展，包括阿尔茨海默病（AD）、帕金森病（PD）等。作为中枢神经系统中的主要免疫细胞群体，小胶质细胞既介导其正常发育，又接收来自母体生物体的病理刺激。这可能导致小胶质细胞过早激活，并可能成为胎儿中枢神经系统发育改变机制的一部分。在这篇综述中，我们讨论了小胶质细胞产前激活在神经精神疾病和神经退行性疾病发展中的作用。我们强调了模拟MIA的方法，以及在生理条件下小胶质细胞形态和功能状态的性别差异。文中还讨论了关于这些差异对男性和女性神经精神疾病以及神经退行性疾病的发病率、患病率和进展的影响的假说。
