Overall effects of microplastics on brain

Su-jun Fang^1,2Zhao-di Yin³Li-fan Li²Qi Cai⁴Peng-fei Zheng⁵Li-zhen Chen^1,2*

• ¹Putian University, Putian, Fujian Province, China
• ²The First Hospital of Putian City, Putian, China
• ³Peking University People's Hospital, Beijing, Beijing Municipality, China
• ⁴Nankai University, Tianjin, China
• ⁵University of Science and Technology of China, Hefei, Anhui Province, China

Abstract 4 Microplastic (MP) and nanoplastic (NP) pollution represents a pervasive 5 environmental issue, raising significant concerns regarding potential neurotoxicity 6 and impacts on brain health. This review synthesizes recent research findings to 7 provide a comprehensive overview of the effects of MPs/NPs on the brain. 8 Evidence demonstrates that MPs/NPs can cross critical biological barriers, 9 including the blood-brain barrier and the placenta, gaining access to the central 10 nervous system (CNS) and the developing fetal brain, influenced by particle size, 11 charge, and the biomolecular corona. Once present, MPs/NPs trigger multiple 12 detrimental pathways, including oxidative stress, persistent neuroinflammation 13 involving microglia and astrocytes, mitochondrial dysfunction leading to energy 14 deficits, disruption of crucial neurotransmitter systems, and direct neuronal 15 damage. Critically, NPs have been shown to promote the aggregation of proteins 16 implicated in neurodegeneration, such as alpha-synuclein. These mechanistic 17 disturbances translate into observable adverse outcomes in experimental models, 18 ranging from cognitive impairments in learning and memory to behavioral 19 abnormalities and pathologies resembling human neurodegenerative and 20 neurodevelopmental disorders. Toxicity is modulated by particle characteristics, 21 co-exposures, and host factors like age and sex, with indirect effects via the 22 gut-brain axis also playing a significant role. While current evidence, primarily 23 from animal models often using high doses, strongly indicates a neurotoxic 24 potential, significant research gaps remain concerning human risk assessment 25 under chronic, low-level environmental exposure conditions and the effects of 26 environmentally aged, mixed-plastic particles. Future research should prioritize 27 human studies, environmentally realistic exposure scenarios, and differentiating 28 direct versus indirect neurotoxic mechanisms to accurately evaluate the threat 29 MPs/NPs pose to human brain health. 30