Why do men and women often respond differently to the same drug, the same stress, or the same brain condition? Worcester Polytechnic Institute (WPI) neuroscientist Jagan Srinivasan has been awarded $554,599 from the National Institutes of Health (NIH) for a three-year project that looks to an unlikely source for answers: a soil-dwelling worm the size of an eyelash.
Srinivasan, a professor in the Department of Biology and Biotechnology and director of WPI’s Neuroscience program, will investigate how Caenorhabditis elegans, or C. elegans—a nematode with a nervous system so simple that scientists have mapped every one of its roughly 300 neurons—responds to a pheromone that normally signals mating opportunities.
C. elegans has two biological sexes: males and self-fertilizing hermaphrodites. Even with nearly identical brain wiring, however, male and hermaphrodite worms respond differently to the same mating pheromone. Srinivasan’s lab will study how worms learn to avoid this pheromone and how serotonin—the same brain chemical that helps regulate mood in humans—can dial that avoidance behavior up or down depending on sex.
“Brain disorders can be difficult to treat,” Srinivasan says. “One challenge is that the activities of our brain are regulated by more than one chemical at a time. Understanding these signals and why sex differences may determine human reactions could help us build the next generation of drugs for human brain disorders.”
The project focuses on neuropeptides, small molecules that act as chemical messengers in the brain, and how they enable two versions of essentially the same neural circuit to produce two different behaviors. It’s a question with implications beyond worms. Many human psychiatric and neurological conditions, from depression to anxiety disorders, show sex-based differences in treatment response, and the underlying biology remains poorly understood.
