小胶质细胞,存在于中枢神经系统(CNS)中的内在神经免疫细胞,对大脑发育产生重要影响,稳态,和功能,涵盖衰老和病理状态期间的关键作用。在理解大脑可塑性和功能方面的最新进展突出了男性和女性大脑之间的明显差异,特别是在神经发生中,神经元髓鞘形成,轴突成束,和突触发生。然而,小胶质细胞对性别特异性脑细胞可塑性的精确影响,雕刻不同的神经网络架构和电路,在很大程度上仍未探索。本文旨在阐明目前对小胶质细胞参与大脑发育的理解,可塑性,和功能,特别强调大脑性别多态性中的小胶质细胞信号。开始概述中枢神经系统中的小胶质细胞及其相关的信号级联,随后,我们探讨了有关小胶质细胞在性别依赖性大脑发育可塑性中的分子信号传导的最新启示,功能,和疾病。值得注意的是,C-X3-C基序趋化因子受体1(CX3CR1),在骨髓细胞2(TREM2)上表达的触发受体,钙(Ca2+),载脂蛋白E(APOE)作为分子候选物出现,显着促进性别依赖性大脑发育和可塑性。总之,我们致力于围绕小胶质细胞在发育和衰老大脑的功能多样性中的关键作用的新兴调查,考虑它们对神经退行性疾病中按性别定制的治疗策略的潜在影响。
Microglia, the intrinsic neuroimmune cells residing in the central nervous system (CNS), exert a pivotal influence on brain development, homeostasis, and functionality, encompassing critical roles during both aging and pathological states. Recent advancements in comprehending brain plasticity and functions have spotlighted conspicuous variances between male and female brains, notably in neurogenesis, neuronal myelination, axon fasciculation, and synaptogenesis. Nevertheless, the precise impact of microglia on sex-specific brain cell plasticity, sculpting diverse neural network architectures and circuits, remains largely unexplored. This article seeks to unravel the present understanding of microglial involvement in brain development, plasticity, and function, with a specific emphasis on microglial signaling in brain sex polymorphism. Commencing with an overview of microglia in the CNS and their associated signaling cascades, we subsequently probe recent revelations regarding molecular signaling by microglia in sex-dependent brain developmental plasticity, functions, and diseases. Notably, C-X3-C motif chemokine receptor 1 (CX3CR1), triggering receptors expressed on myeloid cells 2 (TREM2), calcium (Ca2+), and apolipoprotein E (APOE) emerge as molecular candidates significantly contributing to sex-dependent brain development and plasticity. In conclusion, we address burgeoning inquiries surrounding microglia\'s pivotal role in the functional diversity of developing and aging brains, contemplating their potential implications for gender-tailored therapeutic strategies in neurodegenerative diseases.