July 16, 2013. Mice carrying a genetic glitch associated with mental illness have problems with flexible thinking and motivation, according to a report published July 8 in the Proceedings of the National Academy of Sciences. Led by Akira Sawa and Michela Gallagher, both at Johns Hopkins University in Baltimore, Maryland, the researchers also found signs of oxidative stress, a condition marked by too many oxygen-related molecules that can damage neurons, in the brains of these mice. The results suggest that calming oxidative stress may be a treatment strategy for psychiatric disorders, including schizophrenia and major depressive disorder.
The researchers engineered mice to carry fragments of a protein called DISC1 (for disrupted in schizophrenia 1). These short versions of DISC1 are suspected to occur in humans who have inherited the faulty DISC1 gene and who are predisposed to mental illness. In tasks testing whether mice could learn new rules or work for a reward, mice carrying the short DISC1 struggled. In addition, their brains contained signs of oxidative stress in the prefrontal cortex, a brain region crucial for these behaviors. This suggests that problems with DISC1 translate into troubles for the prefrontal cortex, which can result in the thinking problems and apathy found in mental illness. (For more details, see the related news story.)—Michele Solis.