Polystyrene nanoplastics were evaluated in an A53T α-synuclein mouse model to assess gastrointestinal, metabolic, hepatic, and neurologic outcomes after chronic exposure. In this study, published in npj Parkinson’s Disease, mice were fed polystyrene nanoplastics every other day for three months. This followed intestinal administration of A53T α-synuclein to mimic Parkinson's disease pathology.
The researchers found that mice exposed to nanoplastics had fewer mucus-producing cells in part of the small intestine and more cell death in the gut lining. This happened whether or not the mice carried the A53T α-synuclein gene mutation. The gut bacteria of nano-plastic exposed mice also differed, showing a wider mix of microbes than the control mice, including more of a type of bacteria called Desulfovibrio. Earlier studies have linked this bacterium to the production of hydrogen sulfide—a gas that can damage cells — and to the clumping of the protein α-synuclein. Additional analyses showed that biological pathways related to cell death and the production of inflammatory molecules were more active in the nanoplastic-exposed mice.
Metabolomic profiling of fecal samples identified more than 5,000 metabolites, of which more than 200 showed significant changes in nanoplastic-exposed mice. Many of these altered metabolites were involved in the processing of amino acids, fats, foreign chemicals, and certain drugs. The study also reported significant changes in specific metabolites – including phenylacetylglycine, glycodeoxycholic acid, 7-ketodeoxycholic acid, and 5-hydroxyindole. Histopathologic evaluation of liver tissue demonstrated signs of inflammation in nanoplastic-exposed mice, while levels of cell death in the liver did not differ greatly.
Mass spectrometry of brain tissue detected higher concentrations of A53T α-synuclein when nanoplastics were co-administered. Brain tissue from exposed mice also showed elevated interleukin-6 and lipopolysaccharide levels, and intestinal microbes showed elevated generation of lipopolysaccharide.
Researchers noted that future investigations should include polyethylene, polyamide, charge-neutral particles, and larger microplastic controls to distinguish general nanoplastic effects from those observed with polystyrene. They also indicated that larger, sex-balanced cohorts will be needed to evaluate potential sex-specific responses, as the current sample size limits conclusions in this area.
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