Maternal Immune Activation and Neurodevelopmental Disorders: Integrating Molecular, Cellular and Systems Mechanisms
Yong Qi, Chao Zhao, Lu Xia, Tengfei Zhu, Kun Xia
Abstract
Neurodevelopmental Disorders (NDDs) represent chronic cerebral dysfunctions arising from gene-environment interactions, encompassing conditions such Autism Spectrum Disorders (ASD) and attention-deficit/hyperactivity disorders (ADHD). Emerging evidence identifies Maternal immune activation (MIA) as a critical environmental risk factor for NDDs. Gestational infections, inflammatory responses, or immune dysregulation elevate maternal-fetal inflammatory mediators, which disrupt neurodevelopmental trajectories via placental-fetal signaling cascades. Preclinical models (rodents, non-human primates) demonstrate that MIA induces characteristic NDD phenotypes-including social deficits and cognitive impairments-through microglial hyperactivation, aberrant synaptic pruning, oxidative stress, and mitochondrial dysfunction. Concurrently, gut microbiota dysbiosis and Th17/Treg immune imbalance exacerbate neuroinflammatory processes. Novel therapeutic strategies targeting inflammatory pathways microglial modulation, or microbial homeostasis restoration show translational promise. Future investigations must unravel MIA's molecular underpinnings and multifactorial interactions to enable early-risk stratification and precision interventions for NDDs.