Healthy mice show resilience to chronic nano- and microplastic exposure in the brain

Micro- and nanoplastics (MNPs) have recently been detected in multiple human tissues, including the brain, raising concerns regarding their potential contribution to neuroinflammation and neurodegeneration. However, whether chronic exposure to MNPs is sufficient to perturb the healthy central nervous system remains unresolved. Here, we combined spatial transcriptomics, flow cytometry, blood-brain barrier analyses, microglial morphometry, inflammatory profiling, and behavioural testing to define how chronic oral exposure to micro- and nanoplastics affects the healthy young mouse brain. Spatial transcriptomics identified subtle alterations in cellular neighbourhood organisation and modest transcriptional remodelling across multiple cell populations, including endothelial cells and macrophages. Nevertheless, chronic MNP exposure did not cause detectable blood-brain barrier leakage, alter brain immune cell composition, induce overt microgliosis or astrogliosis, or trigger elevated cytokine production. Likewise, extensive behavioural phenotyping across oral gavage and dietary exposure paradigms failed to reveal detectable impairments in locomotion, anxiety-like behaviour, cognition, or fear conditioning. Together, our findings demonstrate that, under the chronic oral exposure conditions and endpoints tested, healthy young mice display substantial resilience to MNP exposure in the brain. These findings establish an important baseline for future studies investigating whether inflammatory, metabolic, or neurodegenerative conditions sensitize the brain to MNP-associated pathology.