Emerging role of microglia in the developing dopaminergic system: Perturbation by early life stress

作者：Kaijie She, Naijun Yuan, Minyi Huang, Wenjun Zhu, Manshi Tang, Qingyu Ma, Jiaxu Chen · 发表于：Neural Regeneration Research · 年份：2024 · DOI：10.4103/nrr.nrr-d-24-00742 · 被引用次数：17 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Stress Responses and Cortisol、Nuclear Receptors and Signaling

Early life stress correlates with a higher prevalence of neurological disorders, including autism, attention-deficit/hyperactivity disorder, schizophrenia, depression, and Parkinson's disease. These conditions, primarily involving abnormal development and damage of the dopaminergic system, pose significant public health challenges. Microglia, as the primary immune cells in the brain, are crucial in regulating neuronal circuit development and survival. From the embryonic stage to adulthood, microglia exhibit stage-specific gene expression profiles, transcriptome characteristics, and functional phenotypes, enhancing the susceptibility to early life stress. However, the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood. This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia, leading to dopaminergic system disorders, along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions. Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support (e.g., insulin-like growth factor-1) and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning. Furthermore, blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission. Furthermore, inflammation and oxidative stress induced b...