Chronic exposure to noise levels as loud as those in a busy restaurant led to Parkinson’s disease-like characteristics in mice.
Frequent rock concert attendees, those who work in manufacturing, or even people living in dense cities may want to invest in ear protection. Researchers at the Huazhong University of Science and Technology discovered that chronic exposure to loud noise led to irreversible movement defects due to dopamine neuron death in a mouse model of early Parkinson’s disease.1 The findings, which were published in PLOS Biology, revealed a previously unknown link between the brain regions involved in auditory processing and movement and the potential role of environmental noise exposure in Parkinson’s disease.
Genetics, the environment, and lifestyle factors contribute to the risk of developing Parkinson’s disease.2 Prior research has shown that chronic exposure to loud noise associates with multiple neurological conditions, including Alzheimer’s disease and Parkinson’s disease, but whether there was a mechanistic link between the two was unknown.3,4
To answer this question, the researchers, led by neuroscientist and study coauthor Pei Zhang at Huazhong University of Science and Technology, took a mouse model of pre-symptomatic Parkinson’s disease and exposed the animals to loud noises from 85 to 100 decibels—essentially the volume of noise inside a busy restaurant to a motorcycle revving its engine—for one hour as an acute noise exposure. They found that the mice showed motor defects right after the sound exposure, but when the researchers tested the mice again 24 hours later, their movements were back to normal. The researchers also found that the mice had no loss of dopamine neurons in the substantia nigra, the brain region where dopamine neuron loss occurs as a key characteristic of Parkinson’s disease.
However, when the researchers chronically exposed their mouse model to loud sounds for one hour per day for seven days in a row, the mice had significant motor impairments that did not improve even one week later. When they looked in the mice’s brains, they saw significant dopamine neuron loss in the substantia nigra.
To uncover the potential neural circuits involved, the researchers looked to the inferior colliculus (IC), which is a brain region that processes sound. They found that exposure to loud noise led to increased activity of dopamine neurons in the substantia nigra, and when they inhibited the IC neurons, dopamine neuron activity decreased.
Due to this connection, the researchers wondered if optogenetically activating IC neurons would lead to the same motor defects induced by loud noise. When they did a short-term activation of the IC neurons using blue light, the mice had motor defects but did not lose dopamine neurons in the substantia nigra, replicating the results of the acute noise exposure. However, chronic activation of these neurons led to dopamine neuron loss and movement troubles.
But what about the opposite: Could inhibiting the IC neurons protect against these Parkinson’s disease-like changes? Indeed, the researchers found that chemically inhibiting IC neurons before acute or chronic noise exposure prevented both dopamine neuron loss in the substantia nigra and motor defects.
Finally, to better understand the molecular mechanisms involved, the team performed transcriptomics on dopamine neurons after noise exposure, and they found that expression of the gene vesicular monoamine transporter 2 (VMAT2)—which is important for transporting dopamine—was significantly reduced. In fact, when the team activated the IC-dopamine neural circuit without any noise exposure, the researchers saw reduced VMAT2 protein expression in the substantia nigra. However, when the researchers overexpressed VMAT2 in either the IC or the dopamine neurons in the presence of noise, it protected the mice from movement changes and neuron loss, pointing to a new potential therapeutic path.
“Our study reveals that environmental noise exposure changes the IC-[substantia nigra] circuit, leading to motor deficits and increased neuronal vulnerability in a Parkinson’s disease mouse model. This highlights the potential role of environmental factors in exacerbating Parkinson’s Disease pathogenesis,” said the authors in a press release.
