Parkinson’s disease is an especially pernicious neurodegenerative disorder. Instead of a single cause, the illness develops as a result of a combination of genetics, aging, and environmental factors. It’s also around twice as common in men as women. And researchers, such as Julia Schulze-Hentrich of the Center for Gender-Specific Biology and Medicine in Germany, are eager to find out why.
One of the environmental factors linked to Parkinson’s is exposure to pesticides, so Schulze-Hentrich focused her earlier work on agricultural workers. Comparing blood samples from workers with early signs of Parkinson’s and healthy controls showed differences in epigenetic markers between the sexes, which alter gene expression. Women with the disease had DNA methylation changes in 69 regions of the genome, while men only had two.
To get a better understanding of these changes, Schulze-Hentrich and her colleagues investigated the gene expression patterns in post-mortem brain tissue samples from women and men with Parksinon’s as part of a study being presented this week at a conference of the Federation of European Neuroscience Societies. Although the disease caused similar changes in the brains of both sexes—the regions in question showed signs of being under stress—they found that genetic activity differed between men and women in some key neural cells: astrocytes and oligodendrocytes.
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Astrocytes, star-shaped “support cells,” showed differences in the expression levels of genes linked to mitochondria and energy production. Oligodendrocytes, which are responsible for providing the myelin sheath surrounding neurons, showed differences in the genes responsible for that activity. Importantly, the researchers found these differences between the sexes in all the regions of the brain they surveyed.
“This shows that Parkinson’s disease triggers some shared ‘stress responses’ in everyone’s brain cells, but also there are differences between men and women at the cellular level, especially in how the brain ‘support’ cells manage energy and protect nerve connections,” Schulze-Hentrich explained in a statement. “Our findings help to explain why symptoms and disease progression in Parkinson’s differ between men and women.”
While these new findings may one day lead to more personalized treatments for Parkinson’s, the more immediate effect, according to the team, should be a change in how future Parkinson’s research is conducted. Because of the vast differences in gene expression, they argue data from men and women should no longer be grouped together. Or as Schulze-Hentrich put it, “Our results indicate that it’s crucial to recognize that biology varies between the sexes in Parkinson’s disease research and that, wherever possible, researchers should analyze data separately in males and females instead of pooling everyone together.” 
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Lead image: bill2499 / Adobe Stock
