11/7 Ayhan and Burrows

Ayhan et al. used a genetic approach to model schizophrenia. They used a tTA transgenic mouse expressing the mutant hDISC1 gene. Genetic studies had previously identified DISC1 to be important to schizophrenia in both neurodevelopment and adulthood. In Ayhan et al.’s experiments, mice expressed hDISC1 prenatally, postnatally, pre- and postnatally, or not at all. I liked that they used experimental groups that accounted for problems with the gene that could occur developmentally or during adulthood, when schizophrenia symptoms occur.

Males were used in most experiments, but females were used in some tests, but not all. The tail suspension test and forced swim tests were done only on females. In other tests, like drug induced locomotion and open field interaction test, only males were used. Since they decided to include females in their experiment, it would have been better to see them used in all tests so the results could be more easily compared and interpreted.

Burrows et al. tried to alleviate the effects of knocking out the glutamatergic receptor mGlu5 by providing mice with an enriched environment rather than standard housing. On most of their behavioral tests, they saw that an enriched environment alleviated the schizophrenia related symptoms in mice. They saw many positive results with environmental enrichment, like reduced hyperactivity and less deficit in PPI.  However, environmental enrichment did not improve all aspects of schizophrenia tested; novelty preference in the Y maze was not affected. This research is important because environmental enrichment would be a viable translational approach to treating schizophrenia in humans. Mice began enriched housing at 4 weeks, which is around the time of adolescence in humans. Since symptoms of schizophrenia usually begin to occur shortly after adolescence, the results of this experiment may be useful to humans.

Something that bothered me about the methods was that drug-induced hyperlocomotion preceded prepulse inhibition. Even though the tests were about 3 weeks apart, I was wondering if there were any lasting changes in the brain after the drug was administered that could affect the way mice behaved in PPI.