Micro- and nanoplastics in the central nervous system: Transport pathways, neurotoxicity, and implications for brain disorders

Micro- and nano-plastics (MNPs) are widely distributed across global ecosystems and have been extensively detected in human tissues, including the brain. The levels of MNPs are highly correlated with the occurrence of various brain disorders, suggesting the potential central nervous system (CNS) toxicity of MNPs. In this review, we summarize the major circuits by which MNPs may transport into and out of the CNS, including blood-brain barrier crossing, nasal-to-brain routes, and glymphatic system transport. Small-sized MNPs are difficult to eliminate from the brain, which may explain why MNPs may accumulate in the brain. We further discuss the potential neurotoxic effects of MNPs, such as inducing synaptic and neuronal injury, promoting neuroinflammation, dysregulating the neuroendocrine system, and modulating the gut-brain axis. MNP-induced CNS toxicity follows a pattern in which increased susceptibility occurs before direct toxicity. We also review evidence that MNPs, together with environmental and genetic factors, may synergistically contribute to cognitive impairment in Alzheimer's disease, motor dysfunction in Parkinson's disease, and depression- and anxiety-like behaviors. Prenatal exposure to MNPs might induce autism spectrum disorder-related phenotypes in offspring. MNPs could also obstruct cerebral vessels and trigger acute cerebrovascular diseases, as well as promote the entry of viruses such as SARS-CoV-2 into the CNS, thereby increasing the occurrence of neurological symptoms. Finally, this review discusses physical, pharmacological, and plastics substitution interventions designed to regulate MNPs transport in the brain and enhance neuroprotection, thereby reducing CNS toxicity of MNPs.