Week 7: Burrows et al and Ayhan et al

This week's papers continued to discuss animal models of schizophrenia.

In Ayhan et al.'s paper, transgenic mice were used to show the different effects of a mutant hDISC1 protein expressed during various times of neurodevelopment. Table 1 is extremely useful in summarizing the results, showing that the Pre+Postnatal expression group, followed by the Postnatal expression group, had the largest amount of significant changes. Ayhan et al looked at behavior, pharmacological effects, dendritic spine density, brain and ventricle volumes, and endogenous levels of DISC1 and LIS1 in order to better understand the mechanisms of mutant DISC1. I enjoyed the fact that such a variety of tests were used, giving a fuller picture and addressing many aspects of schizophrenia. I was left with a few questions regarding some of the results and figures, but it seems that despite the progress that has been made, there is quite a bit more research needed before some of those questions can be answered. This paper suggested the direction for that research to go, including further research on gender, specific postnatal timing, discriminating between immature/mature dendrites, etc., so I hope that they are able to move forward in further studies.
Ayhan et al proposed many explanations and possible mechanisms for the results they saw, which I appreciated. I also liked that they provided gender-specific results, allowing us to see the differences and similarities between genders in this mouse model. This is something we haven't seen so far in any of the paper we've discussed.
Since enlarged lateral ventricles are a characteristic of schizophrenia, I thought it was interesting that they suggested DISC1 as a possible biomarker after finding that it caused the enlargement of the ventricles as well as many other features of schizophrenia. Overall, I found this paper to have many interesting findings, but more more research is needed to explain some of the results obtained here.

Burrows et al presented a different approach than what we've seen so far in our models of schizophrenia. By using environmental enrichment, they were able to show the strong effects it can have on reversing behavioral deficits caused by an mGlu5 knockout. I found it especially interesting that some of these results were compared to the effects of clozapine, an antipsychotic used to treat symptoms of schizophrenia, because this shows the potential for an alternative treatment. As with any other study that has potential human application, I wonder how translatable to humans these results are, especially given the controversy and lack of understanding of the mechanisms of schizophrenia. I'm curious if enriched environment has been used a treatment in humans before, and what it consists of.

In last week's papers, many of us expressed the desire to see a combination of the two studies. I feel similarly here - it would be interesting to see if environmental enrichment has the same effects in the mutant DISC1 mice. Throughout this class, I've learned that there are so many factors that affect mental illness, meaning that there can't be just one proper way to model a mental disease. However, I think combining these two studies and conducting further research based upon these papers would allow us to get closer to modeling schizophrenia in animals and to finding potential treatments.