A mechanism that may selectively silence the electrical activity of dopamine producing neurons is suggested in a paper in December's Nature Neuroscience.
The slowed movements, rigidity and tremor in Parkinson's disease are caused by a reduction in the neurotransmitter dopamine, following the death of certain dopamine-producing neurons. What makes these neurons particularly vulnerable is not known, but this newly observed silencing could ultimately reduce their survival.
A common observation in Parkinson's disease and its animal models is reduced activity of the cell's power plants, the mitochondria, which produce energy in the form of a molecule called ATP. Birgit Liss and colleagues report that reduced levels of ATP decreased the electrical activity of the vulnerable neurons more strongly than in other neurons that do not die in the disease. The electrical silencing depended on an electrical current normally inhibited by ATP. Toxins that reduce mitochondrial function, which are used to produce animal models of Parkinson's disease, also silenced the vulnerable neurons. Compared to normal mice, mice genetically altered to lack the ATP-sensitive current showed less neuron death in response to these toxins. These results suggest that silencing of electrical activity in these neurons might contribute to their selective vulnerability in Parkinson disease and its animal models.
Birgit Liss (Marburg University, Marburg, Germany)
Abstract available online.
(C) Nature Neuroscience press release.
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