Environmental noise-induced changes to the IC-SNc circuit promotes motor deficits and neuronal vulnerability in a mouse model of Parkinson’s Disease

TL;DR

Exposure to loud noise worsens Parkinson's disease symptoms in mice by affecting a specific brain circuit.

Contribution

The study reveals a new role of the IC-SNc circuit in linking environmental noise to Parkinson's disease progression.

Findings

Acute noise exposure causes temporary motor issues in early-stage Parkinson's mice.

Chronic noise exposure leads to permanent motor deficits and neuron loss in the SNc.

The IC-SNc circuit activation down-regulates VMAT2, contributing to Parkinson's vulnerability.

Abstract

Emerging clinical evidence suggests a link between environmental noise and the severity of Parkinson’s disease (PD). However, the effects of high-decibel noise exposure on PD and its underlying mechanisms remain unclear. In this study, we demonstrate that acute noise exposure induces reversible motor deficits in subacute low-dose 6-hydroxydopamine (6-OHDA) mice, a model of presymptomatic early-stage PD, while chronic noise exposure results in irreversible motor deficits and significant loss of substantia nigra compacta (SNc) dopaminergic (DA) neurons. Additionally, noise exposure activates the inferior colliculus (IC), which sends monosynaptic projections to SNcDA neurons. Optogenetic or chemogenetic bidirectional activation or inhibition of the IC-SNc circuit can mimic or reverse the 6-OHDA vulnerability caused by acute or chronic noise exposure. Mechanistically, noise exposure and IC-SNc circuit activation down-regulate vesicular monoamine transporter 2 (VMAT2) in the SNc, and overexpression of VMAT2 in IC-innervated SNcDA neurons ameliorates noise exposure-induced 6-OHDA vulnerability. Our findings uncover a previously unappreciated role of the IC-SNc circuit in early-stage PD mice in response to environmental noise, which has significance for preventing the onset and progression of PD and highlights the need for environmental harmony to reduce neurodegeneration.

Prolonged exposure to environmental noise has been associated with the occurrence neurodegenerative diseases. This study demonstrates that environmental noise promotes the onset of Parkinson's disease phenotypes in a mouse model and shows that the IC-SNc circuit mediates this increased susceptibility.

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