Depression affects women nearly twice as much as men, but unraveling the brain’s blueprint that regulates this behavior, let alone identifying specific molecular differences between sexes, has proven difficult.
In a new study, researchers have found and flipped a switch in the brain, revealing a single circuit that may activate during stress and is controlled by testosterone.
The research was conducted by a team from Michigan State University.
The team focused on the activity between neurons in the ventral hippocampus, which become active under stress and emotion, and their activation of nucleus accumbens neurons, critical players in reward and motivation.
They found that the activity in male brains during stress was much lower than in females, and this required testosterone.
When they removed testosterone, however, the male mice began expressing depression-like behaviors.
Conversely, the team found increased circuit activity in female brains, but when testosterone was introduced, the neurons quieted, and the female mice became resistant to depression-like behaviors.
The researchers say that what makes these findings stand out is not only identifying this new circuit, but also observing and confirming how it drives different behaviors in males and females.
In the study, the team used chemo-genetic tools to manipulate specific circuit activity in the mouse brain in this study.
Such tools may inform the development of “genetic medicine” for the treatment of human diseases in the future.
The lead author of the study is A.J. Robison, an MSU physiologist.
The study is published in Biological Psychiatry.
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