An overview of research on the association between microplastics and central nervous system disorders

The paper frames microplastics (<5 mm; nanoplastics <1 µm) as pervasive pollutants originating from breakdown of macroplastics and everyday sources (tires, textiles, personal care products). They are found in aquatic and atmospheric environments and can enter organisms via inhalation, ingestion, dermal absorption, and potentially the olfactory route. Microplastics act as vectors for chemical contaminants and, due to small size, can penetrate biological membranes, accumulate in organs including the brain, and elicit neuroinflammation, oxidative stress, cytotoxicity, and hormonal disruption. The study’s purpose is to synthesize evidence linking microplastic exposure to CNS dysfunction and disease, elucidate mechanisms across molecular, cellular, and organ levels, and inform public health risk assessment and policy.

The review synthesizes evidence on microplastics’ biocompatibility, bioaccumulation, and CNS effects. Smaller particles, specific shapes, surface charges, and compositions increase uptake and biodistribution; microplastics <1,000 µm are more readily absorbed. Entry routes include digestive tract, respiratory system, skin, and olfactory pathway enabling potential bypass of the blood–brain barrier. In neural cells, polystyrene nanoplastics reduce viability, induce astrogliosis and apoptosis, downregulate BDNF, and disrupt BBB integrity with size-dependent uptake and toxicity; 0.2 µm particles show greater uptake and damage than 1.0 µm, and inflammatory conditions enhance toxicity. Neurodevelopmental impacts include maternal PS-NP exposure reducing fetal cortical thickness, disturbing neuronal migration and synaptic structure, leading to anxiety-like behavior and memory deficits; PS-NPs cross the placenta and accumulate in cerebellum, hippocampus, striatum, and prefrontal cortex, impairing myelination (reduced MBP/MOG, thinner myelin, increased apoptosis) and motor function. Human stem cell-derived cortical spheroids exposed long-term show decreased viability and downregulated neuronal markers (β-tubulin III, TBR1/TBR2), with smaller particles more readily endocytosed. Mechanistic sections map microplastics to CNS disorders via MIDNIGHTS categories: metabolic (gut microbiota dysbiosis, lipid/glucose metabolism disruption; reduced colonic mucin; decreased oxytocin in mPFC; BBB damage), inflammatory (glial activation, cytokine changes, intestinal permeability alterations; microglial inflammatory responses), neurodegenerative (BBB crossing; energy metabolism and mitochondrial dysfunction; proteostasis impairment; α-synuclein amyloidogenesis and gut–brain transmission; impaired Aβ clearance via microglial dysfunction; glymphatic disruption with elevated Aβ and P-Tau), neoplasms (toxicity to neuroblastoma cells), infectious (acting as pathogen vectors; immune gene downregulation facilitating viral replication; human CSF data linking PP/PE to BBB impairment), neuroendocrine (reduced sociability and oxytocin via gut–brain axis), genetic (RNA/DNA damage; large sets of DEGs/miRNAs/circRNAs linked to synaptic dysfunction), toxic encephalopathy (adsorbing toxic chemicals; neuronal microtubule disruption; biofilm-amplified neurotoxicity), and stroke (inflammation and oxidative stress, vascular dysfunction, capillary occlusion). The lung–brain axis is highlighted: inhaled PS-MPs induce hippocampal structural damage, pulmonary injury, microbiota disruption and LPS release, microglial M1 polarization, and cognitive impairment. Mitigation evidence includes vitamin D reducing NPs accumulation and anxiety-like behaviors by modulating the brain–gut–virome, vitamin K2 normalizing inflammatory and cell death gene expression and reducing neuroinflammation, FGF1 suppressing lipophagy to alleviate neuroinflammation and cognitive deficits, and luteolin modulating G6PD/glutathione-dependent pathways to reduce ferroptosis.

- Microplastics enter via ingestion, inhalation, dermal contact, and possibly the olfactory pathway, accumulate in brain regions, and induce neuroinflammation, oxidative stress, cytotoxicity, and hormonal disruption. - In a BBB model, 0.2 µm polystyrene microplastics had higher uptake and toxicity than 1.0 µm; permeability increased 15.6-fold (24 h) and 27.3-fold (72 h), and TNF-α–induced inflammation enhanced uptake and toxicity. - Maternal PS-NP exposure reduced fetal cortical thickness, disrupted neuronal migration and hippocampal synapses, and caused anxiety-like behavior and spatial memory deficits; PS-NPs selectively accumulated in fetal cerebellum, hippocampus, striatum, and prefrontal cortex, reducing MBP/MOG and myelin thickness, increasing apoptosis, and impairing motor function. - Long-term exposure in human cortical spheroids decreased viability and downregulated neuronal maturation markers (β-tubulin III, TBR1/TBR2); smaller microplastics were preferentially endocytosed. - Gut–brain axis disruptions: 50 µm MPs reduced colonic mucin, altered gut microbiota, decreased oxytocin in mPFC, and damaged BBB; 200–800 nm MPs perturbed energy, bile acid, nucleotide, and carnitine metabolism, leading to neurotoxicity and cognitive impairment. - Neurodegeneration: oral PS-NPs crossed the BBB, distributed to cortex, hippocampus, SNc, and striatum, downregulated PD-related pathways, decreased ATP, and induced motor deficits; intestinal epithelial Nrf2 deficiency exacerbated PD-like neurodegeneration with mitochondrial ultrastructural damage. - PS-NH2 exposure elevated cortical/hippocampal Aβ and P-Tau; NF-κB activation impaired AQP4 polarization at astrocytic endfeet, disrupting glymphatic clearance and causing learning-memory deficits. - Inhaled nanoplastics deposited in olfactory bulb, cortex, and cerebellum, reduced locomotion, increased anxiety-like behaviors, and decreased AChE activity; smaller nanoparticles (e.g., 80 nm) had higher neuronal uptake and toxicity. - Human evidence: cross-sectional study of 5,670 children showed higher urinary microplastics were dose-dependently associated with inattentiveness and impaired working memory (Two-Back/Three-Back tasks). - Vascular and stroke-related findings: microplastics detected in carotid plaques; MPs in circulation induced capillary occlusion in cerebellar cortex, reduced blood flow, and triggered neurobehavioral dysfunction; microplastics exacerbated neuronal death after global cerebral ischemia. - Therapeutic mitigation: vitamin D reduced brain (by ~20%) and intestinal NPs accumulation (by ~58.8% and 52.2%), increased 5-HT, and alleviated anxiety-like behavior in zebrafish; vitamin K2 normalized inflammatory and cell-death gene expression and reduced cytokines and ROS; FGF1 suppressed lipophagy, reducing neuroinflammation and cognitive deficits; luteolin mitigated ER Ca2+ imbalance and ferroptosis via G6PD/glutathione axis.

The compiled evidence supports a multifaceted association between microplastics and CNS dysfunction and disease. Microplastics exhibit size- and surface-dependent biocompatibility that facilitates absorption, transport, and accumulation in brain regions through systemic circulation, direct olfactory translocation, and compromised BBB. Mechanisms converge on oxidative stress, neuroinflammation, mitochondrial and energy metabolism disruption, proteostasis impairment, neurotransmission alterations, glymphatic dysfunction, and microbiota-mediated gut–brain and lung–brain axis effects. Developmental vulnerability is pronounced, with maternal exposures affecting neuronal migration, myelination, synaptogenesis, and behavior in offspring. Evidence spans model organisms, human cell systems, and human observational data indicating cognitive associations. The findings have public health relevance, highlighting microplastics as emerging risk factors for neurodevelopmental, neurodegenerative, inflammatory, vascular, and neuroendocrine conditions, and provide a basis for risk assessment and environmental policy considerations.

Microplastics can enter the human body via ingestion, inhalation, and dermal contact, permeating multiple organs including the brain and causing neurotoxicity, impaired cell proliferation, and immune suppression across life stages. The review underscores age-independent, multi-organ, and multi-level pathological effects and identifies CNS impacts as complex and critically underexplored. The synthesis provides a foundation for public health risk assessment and environmental policy formulation regarding microplastic exposure and CNS health.