STANFORD, Calif. — Men and women’s brains really do work in different ways, and scientists say it all comes down to their genes. A team from Stanford Medicine discovered over 1,000 genes that are much more active in the brain’s grey matter of one gender or another.
According to researchers, these genes are responsible for programming “rating, dating, mating, and hating.” The findings have implications for a host of diseases including Alzheimer’s, autism, and multiple sclerosis.
“Using these genes as entry points, we’ve identified specific groups of brain cells that orchestrate specific sex-typical behaviors,” says senior author Professor Nirao Shah in a university release.
The relationship guide “Men Are From Mars, Women Are From Venus” is famous for highlighting this phenomenon between the genders. In the international best seller, American author and counselor John Gray claimed men and women are so incompatible they could literally be from different planets.
Experiments on mice now suggest Gray was right. Male and female brains do indeed vary in important ways. Study authors believe their results will also apply to humans, highlighting important differences between the sexes.
“Mice aren’t humans,” Shah notes. “But it’s reasonable to expect that analogous brain cell types will be shown to play roles in our sex-typical social behaviors.”
Women’s reproductive cycles also lead to hundreds of differences
The study analyzed four tiny structures that help the animals reproduce and offspring survive. Other mammals, including humans, share these structures as well. They program a males’ quick determination of a stranger’s sex, females’ receptivity to mating, and maternal protectiveness.
Researchers extracted tissue from the animals which contained neurons enriched with sex hormones. Genes are the blueprints for proteins, which do virtually all of a cell’s work. Activation levels – the rate at which genes copy and convert information – determine its functions.
The team also pinpointed more than 600 differences between female mice in different phases of their estrous cycle, equivalent to a woman’s menstrual cycle.
“To find, within these four tiny brain structures, several hundred genes whose activity levels depend only on the female’s cycle stage was completely surprising,” Prof. Shah explains.
Women’s estrogen levels and those of another hormone, progesterone, wax and wane on a roughly monthly basis, like phases of the moon.
The link between these genes and diseases
Some catalogued genes are risk factors for brain disorders that are more common in either men or women, depending on the particular gene. Autism spectrum disorder is four times more common in men. Of 207 genes which confer high risk, 29 are more active in males, compared to just 10 in females.
Scientists found genes with a link to Alzheimer’s and multiple sclerosis, both of which afflict more women, in an overexcited state among female mice. The researchers speculate males and females need different genes to be working harder. A mutation in a gene that needs high activation may do more damage than one that is just sitting around.
“The frequency of migraines, epileptic seizures and psychiatric disorders can vary during the menstrual cycle,” Shah continues, “and our findings of gene activation differences across the cycle suggest a biological basis for this variation.”
Sex-typical social behaviors have been developing in animals’ brains over millions of years of evolution. Male mice, for example, quickly distinguish the sex of strangers infringing on what they consider their territory.
If an intruder is another male, they immediately attack it. If it is a female, they initiate a “whirlwind courtship.” Female mice, on the other hand, exhibit maternal rather than territorial aggression, attacking anything that threatens their pups. They are much more inclined to guard their youngsters and retrieve any that stray. Their willingness to mate varies powerfully depending on the stage of their cycle.
“These primal behaviors are essential to survival and reproduction,” the professor says, “and they’re largely instinctive. If you need to learn how to mate or fight once the situation arises, it’s probably already too late. The evidence is pretty clear that the brain isn’t purely a blank slate just waiting around to be shaped by environmental influences.”
‘Finding needles within needles’
Previous attempts to find gene differences in male and female rodent brain cells have come up with only about 100, seemingly too few for the numerous profound instinctual behaviors.
“We wound up finding about 10 times that many,” Shah reports, “not to mention the 600 genes whose activity levels in females vary with the stage of the cycle. In all, these add up to a solid 6% of a mouse’s genes being regulated by sex or stage of the cycle.”
Prof. Shah likens the team’s process “finding needles within needles in a haystack.”
“The cells we identified as mission-critical for these sex-typical rating, dating, mating or hating behavioral displays account for probably less than 0.0005% of all the cells in a mouse’s brain,” the study author explains.
Determining what makes mice tick also required separating surrounding cells and examining their genetic contents, one at a time.
“This is probably just the tip of the iceberg,” Prof. Shah concludes. “There’s likely to be many more sex-differentiated features to be found in these and other brain structures, if you know how to look for them.”
The study is published in the journal Cell.
South West News Service writer Mark Waghorn contributed to this report.