The subtypes of brain cells that die in Parkinson’s disease have been identified using new techniques to determine which genes are active in individual cells.
We have shown for decades that Parkinson’s disease, a progressive condition that causes tremors and difficulty moving, is associated with the gradual cell death of a part of the brain called the substantia nigra. The cells in question produce signaling chemicals called dopamine that are involved in motor control, but their exact identity is unknown.
Parkinson’s disease drugs raise dopamine levels in a variety of ways, but their effects wane over time, so more effective treatment is needed, say the Broad Institute at MIT and Evan Makosco at Harvard.
Makosco’s team studied eight substantia nigra cells that agreed to donate their brains for postmortem research, not for Parkinson’s disease.
The researchers have used a relatively new technique called single-cell RNA sequencing. This allows you to analyze individual cells in a tissue to see which genes are active and making proteins. They found that the substantia nigra has 10 different subtypes of dopamine-producing cells.
The researchers then applied the same technique to the brains of 10 people who died of Parkinson’s disease or a similar condition called Lewy body dementia. They found that only one of the brain cell subtypes was reduced. This suggests that many cells of that subtype died during human life.
The brain of a healthy adult has around 100,000 of these cells. “It’s a very small subset,” says Makosko. “It was like looking for a needle in a haystack.”
He said the results should lead to a better understanding of the causes of Parkinson’s disease and ways to evaluate potential treatments. If the cells grow in the plate, they can be used, for example, to test new drugs. Some groups are trying to develop dopamine-producing cells that can be transplanted into the brains of people with Parkinson’s disease.
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