Overworked dopamine neurons burn out, fuelling Parkinson’s‑like damage in mice

# Overworked dopamine neurons burn out, fuelling Parkinson’s‑like damage in mice

*Parkinson’s may be a burnout problem in the brain, not just a breakdown.*

Scientists at Gladstone Institutes report that pushing dopamine neurons to fire for weeks causes them to wither and die—mirroring Parkinson’s disease. The mouse study, published 26 August 2025 in eLife and summarised 3 September 2025 by ScienceDaily, links chronic overactivity to the same selectively vulnerable cells hit in patients. The findings suggest that calming these circuits could slow the disease.

> “An overarching question in the Parkinson’s research field has been why the cells that are most vulnerable to the disease die,” says Ken Nakamura, who led the study.

## What the researchers tested
The team used a chemogenetic switch to boost activity in midbrain dopamine neurons. To mimic long‑term stress, they added the activating drug to the mice’s drinking water, keeping the cells firing for weeks.

> “By delivering CNO through drinking water, we get a relatively continuous activation of the cells,” says first author Katerina Rademacher.

## What happened to the cells
Within days, the animals’ day–night activity was thrown off. After one week, axons from some dopamine neurons began to degenerate; by one month, neurons started to die. Damage hit movement‑controlling substantia nigra neurons, while those tied to motivation were largely spared—just as seen in Parkinson’s.

## Why it matters for Parkinson’s
Overactivity raised baseline calcium and altered genes involved in dopamine handling. Early‑stage patient samples showed similar patterns. Together, the results support hyperactivity as a driver of selective vulnerability and offer a toxin‑free model for testing protective strategies.

## What could come next
The work does not pin down why activity rises in people. Possible causes include genetics, environmental toxins, or compensation for lost cells. If overactivity fuels a vicious cycle, therapies that rebalance firing—potentially including deep brain stimulation—might help protect vulnerable neurons.

### Takeaway
Protecting dopamine neurons may require easing their workload before they burn out.

Read more in the original summary on [ScienceDaily](https://www.sciencedaily.com/releases/2025/09/250902085158.htm).