Many brain disorders vary between the sexes, but how biology and culture contribute to these differences has been unclear. The neuroscientists found an intrinsic biological difference between males and females in the molecular regulation of synapses in the hippocampus. This provides a scientific reason to believe that female and male brains may respond differently to drugs targeting certain synaptic pathways.
“The importance of studying sex differences in the brain is about making biology and medicine relevant to everyone, to both men and women,” said Catherine S. Woolley, senior author of the study and a professor of neurobiology at Northwestern University. “It is not about things such as who is better at reading a map or why more men than women choose to enter certain professions.”
Among their findings, the scientists found that a drug called URB-597, which regulates a molecule important in neurotransmitter release, had an effect in females that it did not have in males. While the study was done in rats, it has broad implications for humans because this drug and others like it are currently being tested in clinical trials in humans. “Our study starts to put some specifics on what types of molecular differences there are in male and female brains,” Woolley said. “We don’t know whether this finding will translate to humans or not, but right now people who are investigating endocannabinoids in humans probably are not aware that manipulating these molecules could have different effects in males and females.”
Specifically, Woolley and her research team found that in female brains the drug URB-597 increased the inhibitory effect of a key endocannabinoid in the brain, called anandamide, causing a decrease in the release of neurotransmitters. In male brains, the drug had no effect. (The difference is not related to circulating reproductive hormones.) The subject of many clinical trials, endocannabinoids are molecules that help regulate the amount of certain neurotransmitters released at synapses, the gap between neurons. These molecules are involved in a variety of physiological processes including memory, motivational state, appetite and pain as well as in epilepsy, a neurological disorder. (Their name comes from the fact that endocannabinoids activate the same neural receptors as the active ingredient in marijuana.)
Understanding what controls the synthesis, release and breakdown of endocannabinoids has broad implications both for normal and pathological brain function, Woolley said.