Effects of Micro- and Nanoplastic Exposure During Critical Developmental Periods on the Central Nervous System: A Systematic Review of Rodent Models.

Micro- and nanoplastics (MNPs) are persistent environmental pollutants capable of crossing biological barriers, including the placenta and the blood-brain barrier, raising concerns about their impact on neurodevelopment. This systematic review synthesizes evidence from experimental rodent models, revealing morphological, molecular, and behavioral alterations associated with developmental MNPs exposure in rodent models and highlighting their potential relevance for understanding neurodevelopmental vulnerability. Following PRISMA guidelines (PROSPERO CRD420251127469), MEDLINE, EMBASE, Scopus and Web of Science were searched without date limits (last search: 18 Aug 2025). The review followed a PECO framework: population: mammalian in vivo models; exposure: MNPs during gestation, lactation, childhood, or adolescence; comparator: non-exposed or vehicle-treated controls; outcomes: behavioral, structural, or molecular central nervous system effects. Study reliability was assessed using ToxRTool. Due to heterogeneity, findings were narratively synthesized by exposure window (prenatal, postnatal, combined prenatal-early postnatal exposure). Of 542 records, 20 studies met inclusion criteria. All included studies used rodents (mice or rats) and evaluated polystyrene, polypropylene, polyethylene, or polyvinyl chloride particles delivered mainly by oral routes. Our analysis identified the central nervous system as an important target of MNPs, with convergent findings across exposure windows revealing oxidative stress and mitochondrial dysfunction, neuroinflammation (microglial/astrocytic activation), apoptosis/ferroptosis, disrupted neurogenesis and myelination, and synaptic/dendritic abnormalities. Neurochemical alterations frequently involved GABAergic and glutamatergic imbalance, with context-specific dopaminergic changes. Behaviorally, MNPs were associated with impaired learning and memory, increased anxiety-like responses, altered sociability, and repetitive/stereotyped behaviors. Several studies suggested microbiota-gut-brain interactions via intestinal barrier disruption, dysbiosis, and systemic inflammation. In rodent models, the available evidence suggests that early-life MNPs exposure may contribute to developmental neurotoxicity, which is characterized by multilevel central nervous system alterations and behavioral impairments. Standardized, environmentally relevant exposure paradigms, sex-stratified analyses, and longitudinal follow-up are needed to clarify dose-response, persistence, and human relevance.