Emerging role of microglia in the developing dopaminergic system:Perturbation by early life stress
Kaijie She1
Naijun Yuan2
Minyi Huang1
Wenjun Zhu1
Manshi Tang1
Qingyu Ma1
Jiaxu Chen3
1.Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,School of Traditional Chinese Medicine,Jinan University,Guangzhou,Guangdong Province,China2.Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,School of Traditional Chinese Medicine,Jinan University,Guangzhou,Guangdong Province,China;Shenzhen People's Hospital,The 2nd Clinical Medical College,Integrated Chinese and Western Medicine Postdoctoral Research Station,Jinan University,Shenzhen,Guangdong Province,China3.Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,School of Traditional Chinese Medicine,Jinan University,Guangzhou,Guangdong Province,China;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing,China
摘要：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 preclinicaI 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 by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress-induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic-pituitary-adrenal axis,the gut-brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.
机标关键词：stresssystemrolelifedevelopingdopaminergicearlyemerging
论文发表日期：2026-01-30
在线出版日期：2025-12-11（本平台首次上网日期，不代表文献的发表时间）
页数：15( 126-140 )
英文信息