A gene found only in men is key to regulating the brain's production of dopamine, a new study shows. The finding offers a clue to why men are more likely than women to develop dopamine-related illnesses such as Parkinson's disease, schizophrenia, and addiction. Together with another new study, the work suggests that women and men have distinctive dopamine-regulating systems.
The gene, called Sry, is found on the Y chromosome and is therefore exclusive to men. Sry determines gender, signaling an embryo's gonads to develop into testes rather than ovaries.
Unexpectedly, the gene also performs a function not related to sex, says geneticist Eric Vilain of the University of California, Los Angeles. The researchers found that Sry makes a protein that controls concentrations of dopamine, a neurotransmitter produced in a central brain region called the substantia nigra. Dopamine carries signals from the brain to the body that control movement and coordination.
In people with Parkinson's disease, dopamine-producing neurons in the substantia nigra start to die off, and the brain gradually loses control of physical movements. Tremors and eventually paralysis result. Men are 1.5 times as likely as women to develop the degenerative disease.
To test the effect of Sry, the researchers suppressed the gene's expression in one side of the substantia nigra of male rats. The rats lost 38 percent of the dopamine-producing neurons on that side, the team reports in the Feb. 21 Current Biology. The rats also suffered Parkinson's-like loss of motor function on the side of the body controlled by the altered portion of the brain.
"What this research implies is that the mechanisms of control and production of dopamine are just different between men and women," Vilain says. He adds that the study provides the first evidence for a nonhormonal factor that produces sex differences in the brain.
Because women's brains also produce dopamine, Vilain suggests that Sry "must compensate for something that's present in females and not males."
Estrogens are one possibility, and they could also explain women's apparent advantage when it comes to Parkinson's disease, says neurologist Charlotte Haaxma of Radboud University's Nijmegen Medical Centre in the Netherlands. She notes that men tend to develop Parkinson's at a younger age than women do. Furthermore, women are more likely to develop a milder form of the illness.
At the World Parkinson Congress in Washington, D.C., on Feb. 22 to 26, Haaxma and her team presented data suggesting that estrogens may control dopamine concentrations and stave off the onset of Parkinson's disease. For 96 women with Parkinson's, the team compared estrogen-boosting or -depleting events, such as pregnancies and menopause. The onset of Parkinson's was delayed by an average of 2.7 years per child born, and each year of fertility beyond the group's average age of menopause held off the disease by half a year.
Vilain agrees that these data suggest that estrogen is probably the factor that drives dopamine regulation in women. Investigating such gender differences in the brain, he adds, is "an emerging field."
Department of Neurology
Nijmegen Medical Centre
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Departments of Human Genetics, Pediatrics, and Urology
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University of California, Los Angeles
Los Angeles, CA 90095-7088
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