Shimamura Tsukasa, Kitashiba Masashi, Nishizawa Kazutaka, Hattori Yuki
Department of Anatomy and Cell Biology, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
Front Cell Neurosci. 2025 Apr 7;19:1552241. doi: 10.3389/fncel.2025.1552241. eCollection 2025.
The interplay between the nervous and immune systems is well documented in the context of adult physiology and disease. Recent advances in understanding immune cell development have highlighted a significant interaction between neural lineage cells and microglia, the resident brain macrophages, during developmental stages. Throughout development, particularly from the embryonic to postnatal stages, diverse neural lineage cells are sequentially generated, undergo fate determination, migrate dynamically to their appropriate locations while maturing, and establish connections with their surroundings to form neural circuits. Previous studies have demonstrated that microglia contribute to this highly orchestrated process, ensuring the proper organization of brain structure. These findings underscore the need to further investigate how microglia behave and function within a broader framework of neurodevelopment. Importantly, recent epidemiological studies have suggested that maternal immune activation (MIA), triggered by various factors, such as viral or bacterial infections, environmental stressors, or other external influences, can affect neurogenesis and neural circuit formation, increasing the risk of neurodevelopmental disorders (NDDs) in offspring. Notably, many studies have revealed that fetal microglia undergo significant changes in response to MIA. Given their essential roles in neurogenesis and vascular development, inappropriate activation or disruption of microglial function may impair these critical processes, potentially leading to abnormal neurodevelopment. This review highlights recent advances in rodent models and human studies that have shed light on the behaviors and multifaceted roles of microglia during brain development, with a particular focus on the embryonic stage. Furthermore, drawing on insights from rodent MIA models, this review explores how MIA disrupts microglial function and how such disturbances may impair brain development, ultimately contributing to the onset of NDDs.
神经系统与免疫系统之间的相互作用在成人生理学和疾病背景下已有充分记载。在理解免疫细胞发育方面的最新进展凸显了神经谱系细胞与小胶质细胞（即驻留在大脑中的巨噬细胞）在发育阶段的显著相互作用。在整个发育过程中，尤其是从胚胎期到出生后阶段，多种神经谱系细胞依次生成，经历命运决定，在成熟过程中动态迁移到其合适位置，并与周围环境建立联系以形成神经回路。先前的研究表明，小胶质细胞有助于这一高度协调的过程，确保大脑结构的正常组织。这些发现强调了进一步研究小胶质细胞在更广泛的神经发育框架内的行为和功能的必要性。重要的是，最近的流行病学研究表明，由病毒或细菌感染、环境应激源或其他外部影响等各种因素引发的母体免疫激活（MIA）会影响神经发生和神经回路形成，增加后代患神经发育障碍（NDDs）的风险。值得注意的是，许多研究表明，胎儿小胶质细胞会因MIA而发生显著变化。鉴于它们在神经发生和血管发育中的重要作用，小胶质细胞功能的不适当激活或破坏可能会损害这些关键过程，潜在地导致异常的神经发育。本综述重点介绍了啮齿动物模型和人类研究中的最新进展，这些进展揭示了小胶质细胞在大脑发育过程中的行为和多方面作用，尤其关注胚胎期。此外，借鉴啮齿动物MIA模型的见解，本综述探讨了MIA如何破坏小胶质细胞功能以及这种干扰如何损害大脑发育，最终导致NDDs的发生。
