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The gut-brain axis involved in polystyrene nanoplastics-induced neurotoxicity via reprogramming the circadian rhythm-related pathways

Journal of Hazardous Materials 2023 89 citations ? Citation count from OpenAlex, updated daily. May differ slightly from the publisher's own count.
Huiwen Kang, Wei Zhang, Jiaru Jing, Danyang Huang, Lei Zhang, Jingyu Wang, Han Lin, Ziyan Liu, Ziyan Wang, Ai Gao

Summary

Researchers found that polystyrene nanoplastics given orally to mice crossed the blood-brain barrier and caused neuronal damage in the hippocampus, the brain region responsible for learning and memory. The nanoplastics disrupted the gut-brain connection by altering gut bacteria and circadian rhythm pathways, leading to measurable declines in learning and memory ability. This study provides a biological mechanism showing how ingested plastic nanoparticles could contribute to brain-related health problems in humans.

Polymers
Body Systems
Models

The production of plastic is still increasing globally, which has led to an increasing number of plastic particles in the environment. Nanoplastics (NPs) can penetrate the blood-brain barrier and induce neurotoxicity, but in-depth mechanism and effective protection strategies are lacking. Here, C57BL/6 J mice were treated with 60 μg polystyrene NPs (PS-NPs, 80 nm) by intragastric administration for 42 days to establish NPs exposure model. We found that 80 nm PS-NPs could reach and cause neuronal damage in the hippocampus, and alter the expression of neuroplasticity-related molecules (5-HT, AChE, GABA, BDNF and CREB), and even affect the learning and memory ability of mice. Mechanistically, combined with the results of hippocampus transcriptome, gut microbiota 16 s ribosomal RNA and plasma metabolomics, we found that the gut-brain axis mediated circadian rhythm related pathways were involved in the neurotoxicity of NPs, especially Camk2g, Adcyap1 and Per1 may be the key genes. Both melatonin and probiotic can significantly reduce intestinal injury and restore the expression of circadian rhythm-related genes and neuroplasticity molecules, and the intervention effect of melatonin is more effective. Collectively, the results strongly suggest the gut-brain axis mediated hippocampal circadian rhythm changes involved in the neurotoxicity of PS-NPs. Melatonin or probiotics supplementation may have the application value in the prevention of neurotoxicity of PS-NPs.

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