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The researchers found gender differences in gene activity in cortical neurons (pictured) and other brain cells.Credit: David Scharf/Science Photo Library
By analyzing more than a million brain cells, the researchers found widespread differences in patterns of gene activity between male and female brains.
The work, which defines gender based on a person’s combination of sex chromosomes, may help explain why the risk of developing certain brain diseases — such as schizophrenia and Alzheimer’s disease — is different for men and women.
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Although the differences were subtle, the team identified more than 100 genes that showed consistent variation in their expression between males and females in several brain regions. The work was published on April 16 in Science1.
“Having these gene expression signatures provides molecular help in understanding the biology of how men’s and women’s brains may function slightly differently in the context of the different hormonal environments their bodies produce,” said Jessica Tolkun, a neuroscientist and molecular biologist at Cold Spring Harbor Laboratory in New York. She adds that “understanding gender differences in disease susceptibility may lead to better treatments that benefit everyone.”
Subtle differences
Previous studies2,3 have documented gender differences when it comes to the risk of developing various neurological conditions. For example, schizophrenia, attention deficit hyperactivity disorder (ADHD) and Parkinson’s disease are more common in biological males – who usually have XY sex chromosomes. In contrast, Alzheimer’s disease and mood disorders such as depression and anxiety are more common in women, whose sex chromosomes are usually XX.
“What underlies this is a central question,” says Tolkun. Gender differences in the brain are usually “extremely subtle,” she explains. “Most of the brain shows no gender differences in its daily function.”
However, molecular-level differences in gene expression between male and female brain cells can “modulate the impact of disease variants,” says study co-author Alex De Cassien, a computational and evolutionary biologist at the US National Institute of Mental Health in Bethesda, Maryland.
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To investigate this, DeCasien and her colleagues examined cells from six regions of the cerebral cortex, identifying about 680,000 excitatory neurons and 290,000 inhibitory neurons, as well as 270,000 glial and other cells in tissue samples from 30 people.
In an analysis of more than 4,300 genes, the team reported that gender accounted for less than 1% of the variation in gene expression in brain cells. “This finding fits with what we already know about human variation—there is much more variation within a sex than between sexes,” says Donna Maney, a neuroscientist at Emory University in Atlanta, Georgia.
