Polystyrene Nanoplastics Hitch-Hike the Gut–Brain Axis to Exacerbate Parkinson’s Pathology

The neurological implications of micro- and nanoplastic
exposure
have recently come under scrutiny due to the environmental prevalence
of these synthetic materials. Parkinson’s disease (PD) is a
major neurological disorder clinically characterized by intracellular
Lewy-body inclusions and dopaminergic neuronal death. These pathological
hallmarks of PD, according to Braak’s hypothesis, are mediated
by the afferent propagation of α synuclein (αS) via the
enteric nervous system, or the so-called gut–brain axis. Here
we first examined the effect of enteric exposure to polystyrene nanoplastics
on the peripheral and central pathogenesis of A53T, a representative
αS mutant. Specifically, the polystyrene nanoplastics accelerated
the amyloid aggregation of A53T αS, which subsequently elevated
the in vitro production of glial activation biomarkers, cytokines,
and reactive oxygen species and compromised mitochondrial and lysosomal
membrane integrity, further shifting cellular metabolite profiles
in association with PD pathophysiology. In vivo, coadministration
of the polystyrene nanoplastics and A53T αS facilitated their
synergistic gut-to-brain transmission in mice, leading to progressive
impairment of physical and motor skills in resemblance to characteristic
PD symptoms. This study provides insights into the response and vulnerability
of Parkinson’s gut–brain axis to polystyrene nanoplastics.