Burrows et. al and Ayhan et. al

I really enjoyed reading the papers this week in comparison with last week. I felt that this research was much more applicable to clinical populations of schizophrenia. In the Burrows et. al (2015) paper, mice with a knockout mGlu5 were separated into two groups one with an environmentally enriched housing and the others with standard housing. The paper found that environmental enrichment can help prepulse inhibition and locomotor hyperactivity, which are both two phenotypes that have been shown to be affected by mGlu5 knockout mice. As we read last week and in this paper this week, lower startle responses in prepulse inhibition can be a test for modeling schizophrenia in animals. I thought showing the role that the environment can play through an animal model on the symptoms of schizophrenia was extremely interesting. I think that this could be readily applied to clinical populations by creating new enriching programs to help cope with their symptoms. If we could target environmental ways that change the regulation of mGlu5 receptors, this could be potentially very beneficial for patients with schizophrenia. 

However, this week I was drawn more to the Ayhan et. al (2011) paper. Another really important aspect of schizophrenia in humans is the later onset of the disease (we also saw this beginning to be studied last week). This paper took a different approach in studying schizophrenia by taking a known human gene (DISC1) that is affected in humans with schizophrenia and mutating this gene in mice and performing various tests. I thought it was interesting that they included male and female mice in this study, which is something throughout the semester that we have not really seen in other animal models. I did think the inclusion of other genders did add to the study, but I also think that there could have been some external factors that may show differences in some of the results. For example, we have talked earlier in the semester about how having an all female or all male lab techs can affect and change the results of certain experiments, so I wondered if maybe an external factor like this could be attributing to the differences in the behavioral tests that are seen in this paper. I thought it was interesting though that this difference throughout the experiments is pretty much only seen in the behavioral tests. Also females and males in the human species have different behaviors, so potentially this is a difference in the evolutionary changes and behaviors that are different between genders. Another interesting part I thought was that in figure 3 they only examined the differences in norepinephrine, 5ht, da, 5hiaa, hva, and dopac and their interactions in the frontal cortex of male mice. Whereas, the same things were studied but only in the hippocampus of females. Maybe I missed this information elsewhere in the paper, but I thought it was interesting that they limited their study to only focus on those particular brain regions in each gender. Although this paper does not give one clear-cut model for schizophrenia it does a couple of really important things: 1) it changed the gene expression of DISC1 at different developmental periods (which is a really important factor for clinical schizophrenia) and 2) it shows that the change in gene expression groups show different features. This may be indicative of the clinical population as well. I think that studying schizophrenia is extremely difficult, because there is such a wide range of symptoms and clinical populations in this disorder, but using animal models to show these differences may be crucial to making differing diagnoses and understanding this disease better. Much later on this could lead to more effective treatments. But all in all, I thought that both of these studies were very translatable to humans than the previous week's papers.