A study team led by researchers at the University of Iowa recently bred mice lacking two types of proteins, SAPAP3 and MC4R, in the brain, and found an unexpected brain circuit interaction between them.
The lead researchers, Andrew Pieper, an associate professor of psychiatry and neurology, M.D., Ph.D. and Michael Lutter, an assistant professor of psychiatry, M.D., Ph.D. at the UI Carver College of Medicine, also included researchers from Stanford University School of Medicine, the University of Texas Southwestern Medical Center, Beth Israel Deaconess Medical Center, and Harvard Medical School. The study was published the week of June 10th in the online early edition of the Proceedings of the National Academy of Sciences (PNAS).
Pieper has an interest in researching compulsive behavior, and his mouse model lacks the brain protein SAPAP3. These mice with compulsive behaviors groom themselves excessively to the point of damaging their skin. The commonly used drug to treat the obsessive-compulsive disorder (OCD) in people is known as fluoxetine.
Lutter is interested in the development of obesity, and he works with mice lacking the brain protein MC4R, which causes a similar form of inherited human obesity. Mutations in the MC4R gene are the most common single-gene cause of morbid obesity and over-eating in people.
A previous study hinted that MC4R might also be a factor of compulsive behavior when it exists in brain, which got Pieper and Lutter thinking about performing tests about the possible interaction of SAPAP3 and MC4R. As a result, the experiment proved their original hypothesis: knocking out and chemically blocking the MC4R protein in the OCD mouse normalized their grooming behavior.
However, this breeding experiment revealed another totally unexpected result when they experimented with both of these two protein deficiencies: loss of the SAPAP3 protein in mice that were obese due to the lack of MC4R, normalized the weight of mice.
Although obesity and obsessive-compulsive behavior may seem unrelated, Lutter suggests that the connection may be rooted in the evolutionary need to eat safe, clean food in times of a food abundance, and to lessen this drive when food is scarce.
“We completely rescued body weight and food intake in the double null mouse. I think this circuit that we have uncovered is probably involved in determining whether or not people should eat calorically dense foods,” Lutter says.