Overworked brain cells may burn out in Parkinson’s disease: Study
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New Delhi: Constant overactivation of brain cells can cause them to degenerate and die, a discovery that may shed light on what happens in the brains of people with Parkinson’s disease, scientists have reported.
While researchers have long known that specific neurons are lost as the disease progresses, the reasons behind their vulnerability have remained unclear. The new study, published in the journal eLife, shows that in mice, prolonged activation of dopamine-producing neurons directly leads to their death.
The researchers suggested that in Parkinson’s disease, this overactivation could be triggered by a mix of genetic predisposition, exposure to environmental toxins, and the brain’s attempts to compensate for lost neurons.
“An overarching question in the Parkinson's research field has been why the cells that are most vulnerable to the disease die,” said Ken Nakamura, investigator at Gladstone Institutes in the US. “Answering that question could help us understand why the disease occurs and point toward new ways to treat it.”
Parkinson’s disease affects more than 8 million people worldwide and is marked by tremors, slow movement, stiff muscles, and difficulties with walking and balance.
In the study, Nakamura’s team engineered mice to carry a receptor in their dopamine neurons that allowed scientists to artificially increase cell activity through a drug added to the animals’ drinking water. This drove persistent overactivation of the neurons.
Within days, the animals showed disrupted sleep–wake cycles. After one week, degeneration was observed in the long axons extending from dopamine neurons. By one month, the neurons themselves had begun to die.
The team also examined the molecular changes in the affected neurons, finding alterations in calcium levels and in genes involved in dopamine metabolism. When they compared these results with brain samples from patients with early-stage Parkinson’s, they discovered similar patterns, reduced activity of genes linked to dopamine metabolism, calcium regulation, and stress responses.