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Post 6: Genetic and environmental effects on mouse models of Schizophrenia

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Schizophrenia is an extremely complex disorder that, like most other psychological disorders, can be impacted by numerous genetic and environmental factors before and after birth. Ayhan et al. and Burrows et al. both explore some of these factors and how they affect neuronal morphology, behavior, and biochemistry in mouse models of schizophrenia. I was excited to see that both papers utilized both male and female disease models, but I was somewhat surprised by the lack of sex effects reported by Burrows, especially given the differential timeline and manifestations of schizophrenia in men and women. I imagine that the lack of sex effects in Burrows, as compared to significant sex effects in Ayhan, may be due to the fact that different genes/proteins with different functions are being manipulated and those manipulations are occurring in different ways. Perhaps the fact that DISC1 is scaffold protein that has a wide range of proteins it binds to accounts, in part, for the presentation of sex differences not seen with mGlu5. Ayhan did report different results between sexes in behavior, monoamine content, and responses to drugs, but did not find any underlying differences in brain morphology or monoamine levels. It seems that further research could be conducted to identify possible sources of differentiation between males and females. I found it especially interesting that some of the behavioral results seem to reflect those seen in humans (females showing more depression-like behaviors and males showing more aggressive behaviors) and would be interested in further exploration to see if this apparent similarity is significant. 

While reading these papers, I also became interested in the importance of temporal precision of the methods in both papers. In Ayhan, the Tet-off system is used with Dox-containing food to temporally control expression of hDISC1 in pre- and post-natal mice. Because so many aspects of development are time-dependent, I wonder how precise this method can be prenatally, and whether results for the prenatal group would differ if Dox was delivered at a different embryonic timepoint. As for Burrows, I am very curious about how changing the timing of environmental enrichment might influence its efficacy in modulating schizophrenia-like impairments. Perhaps earlier postnatal environmental enrichment could further improve schizophrenia-like effects in mGlu5 KO animals. Additionally, I wonder if environmental enrichment of a pregnant mouse could improve the outcome of her offspring, leading to an improved prenatal environment—which can be an important factor contributing to schizophrenia risk. Having a greater understanding of internal and external factors related to schizophrenia during adulthood as well as development is crucial to understanding and decreasing risk of disease. 

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