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Sex on the brain
Gene that helps determine gender linked to Parkinson's disease.

By Carina Dennis
February 20, 2006

Biologists have proof that men do, in fact, have sex on the brain. A crucial sex-determining gene on the male Y chromosome, called Sry, is known to be expressed in the male brain as well as in the testes.

But now researchers have come up with a surprise: Sry's effects on the brain seem to be involved in motor coordination rather than more sex-related traits. And loss of the gene leads to symptoms similar to those of Parkinson's disease.

"It was a big surprise. I was expecting Sry to have more to do with a region involved in sexual behaviour, like the hypothalamus, than a region involved in motor control," says Eric Vilain of the University of California, Los Angeles. "We repeated it many times to be sure," he adds.

Vilain and his colleagues studied Sry proteins in rat brains and found that they occur in the substantia nigra in males; this is a region of the brain involved in motor function and is affected in Parkinson's.

By using injections to block the expression of the Sry gene in this region of the male rat brain, the researchers showed that the mice developed motor problems reminiscent of Parkinson's. When they stopped the injections, the rats recovered.

"We have this prejudice with sex chromosomes. We think they should be expressed in parts of the brain involved in reproductive behaviour. And clearly that's not necessarily the case - this paper really opens our eyes," says Emilie Rissman, a behavioural neuroscientist at the University of Virginia School of Medicine in Charlottesville, Virginia.

Boys will be boys

So what is Sry doing in this part of the brain? All the clues so far suggest that it switches on the expression of tyrosine hydroxylase (TH), an enzyme involved in making a neurotransmitter called dopamine. TH-expressing neurons are sexually dimorphic - there are 20% fewer in females than males, as reported in this study. Sry seems to maintain TH levels in the male: when Sry is turned off, the expression of TH falls. When the gene is turned back on, the neurons recover.

Sry could explain why men are about 1.5 times more likely to develop Parkinson's than women, says Vilain. It could also potentially explain why other dopamine-linked diseases are more common in males, such as schizophrenia and addiction, adds Vincent Harley of Prince Henry's Institute of Medical Research in Melbourne, Australia, who is a co-author on the paper.

Harley is now investigating Sry levels in the brains of human cadavers, comparing levels in men with Parkinson's and those without the disease.

Meanwhile, the team plans to pursue the gene's link to sexual behaviour. Harley notes that their team has also spotted Sry expression in the medial mammillary bodies of the brain. Earlier studies have reported that destroying this region in rodents alters their sexual behaviour, and Harley says there are anecdotal medical case studies showing that damage to this region in people can lead to changes in sexual appetite.

Original source: http://www.nature.com

 

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