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According to a new study, male and female mouse brains are different.
The brains of men and women are likely to be different.
The structures within the mouse brain are known to be used forrating, dating, and hating behaviors. These behaviors help the animals reproduce and their offspring survive, for example, males' quick determination of a stranger's sex, females' receptivity to mating, and maternal protectiveness.
More than 1,000 genes are more active in the brains of one sex than the other, according to an analysis of brain tissue enriched for sex hormones. Most of a cell's work is done by genes, which are the blueprints for the proteins. Gene-activation levels determine a cell's functions.
The findings help explain behavioral sex differences in mammals.
The study's senior author, Nirao Shah, PhD, professor of psychiatry and behavioral sciences and of neurobiology, said that the study identified specific groups of brain cells that orchestrate specific sex-typical behaviors.
The lead author of the study is a graduate student in Shah's lab.
The researchers found more than 600 differences in the levels of genes that are activated in different phases of the estrus cycle. Female mice don't menstruate and this is referred to as the menstrual cycle in women.
Shah, who has devoted his career to understanding how sex hormones regulate sex-typical behaviors, was surprised to find hundreds of genes whose activity levels depend only on the female's cycle stage.
Humans and mammals share the same brain structures.
Shah said that ice aren't humans. It's reasonable to think that brain cell types will play roles in our sex-typical social behaviors.
Insight into mental disorders.
Some of the genes the researchers catalogued are established risk factors for brain disorders that are more common in one or the other sex. The researchers identified 39 genes that are more active in the brains of males and females, which is four times as common in men as in women. They found genes linked to Alzheimer's disease and multiplesclerosis that are more activated among female mice.
The researchers theorize that males and females need different genes to be working harder, and that a high-activated gene in females may do more damage than a low-activated one in males.
Shah said that the menstrual cycle can vary in the frequencies of migraines, epileptic seizures and psychiatric disorders.
Sex-typical social behaviors.
Over millions of years of evolution, sex-typical social behaviors have been built into animals' brains.
Male mice are quick to distinguish the sex of strangers. They immediately attack the man if he is another male. If it's a female, they will initiate a quick courting.
Female mice attack anything that threatens their pups. They are more likely to retrieve strays than males. Depending on the stage of their cycle, their willingness to mate varies powerfully.
Shah said that the behaviors are essential to survival and reproduction. It's probably too late to learn how to mate or fight when the situation arises. The evidence shows that the brain isn't a blank slate just waiting to be shaped by the environment.
Shah's group mused that previous attempts to find differences between male and female brain cells have come up with only about 100 of them.
Shah said that they found about 10 times as many genes as they had originally thought. In all, these add up to a solid 6% of a mouse's genes being regulated by sex or stage of the cycle.
There are needles in a haystack.
Shah likened the methods his team used to find needles.
The cells we identified as mission-critical for these sex-typical rating, dating, mating or hates behavioral displays account for less than 1% of all the cells in a mouse's brain. To determine what made these cells tick, you have to separate them from their surrounding cells and look at their genetic contents one cell at a time.
The researchers vastly improved their prospects by zeroing in on scarce but crucial cells that are responsive to estrogen, which is a major female sex hormone. Estrogen is present in males. Similar female-sex-typical behaviors are found in many mammals, like waxing and waning of hormones, like phases of the moon. The estrus stage is marked by peaks in both hormones' levels and troughs in the hormone levels.
Shah was able to purify tissue from each of the four key brain structures in a way that enriched the resulting brain-cell population for estrogen-responsive cells. The researchers compared males, females in estrus and females in diestrus and found 1,415 genes with activity levels that differed among the groups.
The cells were different. In the brain structure called the bed nucleus of the stria terminalis, there were 36 different cell types that were distinguished by the genes in each cell type that were active in one or another of the mouse groups. Human brains have the bed nucleus of the stria terminalis.
The scientists found that only one of the 36 estrogen-responsive cell types was essential to male mice's ability to quickly recognize the sex of an unfamiliar mouse.
The ventromedial hypothalamus, also known as the human brain, contains 27 estrogen-responsive cell types that are distinguishable by different patterns of gene activation. Knocking out the performance of just one of those cell types, but not of the other 26, changed females who would normally be sexually interested into those who rejected sexual advances even when they were in heat.
The "needles within needles" of the brain are the BNST and the VMH cell types that regulate males' and females' sexual receptivity. Shah said that it was not clear what tasks the other 35 sex-hormone-responsive cell types in the BNST and the other 26 equivalent cell types in the VMH were carrying out.
'Tip of the iceberg'
"This is probably the beginning of something bigger," he said. If you know how to look for sex-differentiated features in brain structures, there's likely to be many more.
The intellectual property associated with the study has been granted a patent by the Office of Technology Licensing.
Adarsh Tantry and Chung are graduate students at the university. The work was contributed to by researchers at Columbia University.
The journal contains information about the cell.
Sex-typical behavior of male and female mice is guided by differences in brain's genes.
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