More than 10 million people in the world suffer from Parkinson’s, a neurodegenerative disease that causes the death of the neurons that are responsible for producing dopamine in our brain, a substance that we need to transmit emotional and motor responses between the different neurons. Therefore, among the symptoms of Parkinson’s, motor disorders such as tremors, muscle rigidity, or balance disorders stand out, although there are others that do not affect movement such as cognitive or gastrointestinal problems, depression or fatigue.
Now, for the first time, scientists from the Broad Institute in Boston (United States) have managed to identify the 10 types of dopaminergic neurons -which are responsible for producing dopamine- and have discovered that one of them is specifically vulnerable to this disease, according to published in the journal Nature Neuroscience.
The results of his study can help to better understand how the disease appears and progresses and to develop new treatments against Parkinson’s, since those currently used contribute to replacing lost dopamine and reducing symptoms, but the neuronal deterioration they experience patients is irreversible.
Neurons especially vulnerable to Parkinson’s disease
The researchers studied 22,000 dopaminergic neurons in human brain samples, some of which came from people who had died with Parkinson’s, and others from individuals who had not been diagnosed with the disease before they died. During the study they measured gene expression in these samples and discovered that there were 10 different subtypes of these cells in the more compact zone of the substantia nigra (an area located in the midbrain of the brain).
“We found 10 types of dopamine neurons in the midbrain, one of which was especially vulnerable to cell death in Parkinson’s disease.”
They found that the subtype that harbors the active AGTR1 showed a greater vulnerability to Parkinson’s, significantly decreasing compared to the rest. Therefore, the results of the work show that Parkinson’s attacks a certain subgroup of dopaminergic neurons, which, having been identified, can facilitate the search for new therapeutic options.
Evan Macosko, an institute fellow at the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard and a psychiatrist at Massachusetts General Hospital and lead author of the research, explained: “Previous studies have suggested that there are two or three types of dopamine neurons in the midbrain. We found 10 types, one of which, marked by the expression of a gene called AGTR1, was especially vulnerable to cell death in Parkinson’s disease. And using Slide-seq, a technology my lab has been developing together with Broad core member Fei Chen, we were able to pinpoint exactly where these particular neurons are within the substantia nigra.”
“Our results help explain a long-standing mystery about Parkinson’s: why this particular subset of dopamine cells dies in the midbrain. These dying cells express more risk-related variants compared to other cell types and to similar cells from people without Parkinson’s. So human genetics act within these cells to make them more vulnerable to cell death, compared to other related dopaminergic neuron subtypes, which don’t die as much and don’t express as many of these risk genes.”
Although only a small number of human brains have been studied in this research, its authors intend to study more brains. Macosko concludes: “We were able to get some pretty interesting insights with a relatively small number of people,” but “when we reach larger numbers of people with other types of illnesses, I think we’ll learn a lot.”
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