By analyzing over 1 million brain cells, the research team found more than 100 genes that showed consistent variation in expression between males and females across various brain regions.
According to the journal Nature, by analyzing more than 1 million brain cells, researchers discovered widespread differences in gene activity patterns between male and female brains.
This groundbreaking finding could help explain why the risk of developing certain brain disorders—such as schizophrenia and Alzheimer's disease—differs between the sexes.
The study, published in the journal Science in mid-April, determined sex based on chromosome combinations. The research team identified over 100 genes showing consistent variation in expression between males and females across various brain regions.
Jessica Tollkuhn, a neuroscientist and molecular biologist at the Cold Spring Harbor Laboratory (New York, USA), praised the discovery: "Having these gene expression markers provides a molecular basis for understanding biologically how the brains of men and women may be functioning slightly differently in the context of the different hormonal environments their bodies create."
She added that "understanding gender differences in disease susceptibility could lead to better treatments that benefit everyone."
Numerous previous studies have noted significant differences in the risk of neurological disorders between the sexes. For example, schizophrenia, attention deficit hyperactivity disorder (ADHD), and Parkinson's disease are generally more common in men (those with XY chromosomes). Conversely, Alzheimer's disease and mood disorders such as depression and anxiety tend to occur more frequently in women (those with XX chromosomes).
"What lies beneath the surface has always been a central question," Tollkuhn shared. She explained that gender differences in the brain tend to be "extremely subtle," emphasizing, "The vast majority of the brain doesn't exhibit gender differences in its everyday functioning."
However, subtle differences at the molecular level play a significant role. Study co-author Alex DeCasien, an evolutionary and computational biologist at the National Institute of Mental Health, said that differences in gene expression between male and female brain cells may "modulate the effects of disease variants."
To reach this conclusion, DeCasien and his colleagues conducted research on tissue samples from 30 people. They analyzed cells from six areas of the cerebral cortex, identifying approximately 680,000 excitatory neurons, 290,000 inhibitory neurons, along with 270,000 glial cells and other cell types.
Through the analysis of more than 4,300 genes, the research team reported that sex actually accounts for less than 1% of the variation in gene expression across all brain cells.
Commenting on this figure, Donna Maney, a neuroscientist at Emory University (Georgia, USA), stated: "This finding is consistent with what we already know about variability in humans – there is more variability within a single sex than between sexes."
Nevertheless, this small percentage opens up promising new avenues for developing more targeted and personalized medical treatments for each gender in the future.