New Delhi, Aug 28 Scientists have showed that when brain cells are constantly overactivated for weeks on end, they degenerate and ultimately die, a finding that may help explain what goes awry in the brains of people with Parkinson's disease.
Researchers have long known that a particular subset of neurons dies as Parkinson's disease progresses, but they weren't sure why.
The new study, published in the journal eLife, shows that in mice, chronic activation of these neurons can directly cause their demise.
The scientists hypothesise that in Parkinson's, neuron overactivation could be triggered by a combination of genetic factors, environmental toxins, and the need to compensate for other neurons that are lost.
"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," Nakamura added.
More than 8 million people worldwide are living with Parkinson's disease -- a degenerative brain disease that causes tremors, slowed movement, stiff muscles, and problems walking and balancing.
In the new study, Nakamura and his colleagues introduced a receptor specifically into dopamine neurons in mice that allowed them to increase the cells' activity by treating the animals with a drug, which was added to the animals' drinking water, driving chronic activation of the neurons.
Within a few days of overactivating dopamine neurons, the animals' typical cycle of daytime and nighttime activities became disrupted. After one week, the researchers could detect degeneration of the long projections (called axons) extending from some dopamine neurons.
Further, the team studied the molecular changes that occurred in the dopamine neurons before and after the overactivation. They showed that overactivation of the neurons led to changes in calcium levels and in the expression of genes related to dopamine metabolism.
When the researchers measured the levels of genes in brain samples from patients with early-stage Parkinson's, they found similar changes; genes related to dopamine metabolism, calcium regulation, and healthy stress responses were turned down.
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