Week 7

Wow, the Ayhan et al paper was packed full of information. It was great to learn a little more about this DISC1 protein that I’ve heard so much about, and I thought it was great that they used a combination of chemical and behavioral tests – very convincing. After finishing this paper, I am convinced that DISC1 has an important role in schizophrenia, pre and postnatally. It makes sense that if the DISC1 protein is acting in a dominant-negative fashion like they propose, that people with DISC1 mutations would experience the effects of the mutation both pre and postnatally. Although they only saw reduced brain volume in the prenatal mice, they didn’t really test any environmental effects coupling with the DISC1 mutation, so I am not ready to throw out DISC1’s role prenatally quite yet. One thing I was concerned about was that they took the postnatal group off Dox on day E12. This seemed a little early to me, especially since it took around 3-5 days to reestablish expression of the mutant DISC1 protein. It could be possible that the mutant DISC1 was present during the last days of development, which from the previous papers we saw are still really important and have a huge effect on resulting phenotype. It would have been nice to see more groups with more temporal specificity, like the authors mentioned in their conclusion (although I am sure someone is working on that now). I was also a little disappointed that they didn’t address any changes in behavior before and after puberty. When they said they ran behavioral experiments between months 3-7 I already got excited and thought they would show some data comparing changes due to puberty. I also thought the sex-differences shown in this paper were really interesting. The fact that the female mice showed depressive behaviors, while the males showed aggressive behaviors was really cool, and made me think about whether there are behavioral differences in female and male people with schizophrenia. I also wondered whether the male’s increase in aggression could be due to an inability to properly interpret social cues from the other mice… Not sure whether inability to read social cues is common in schizophrenia, but it also made me think about autism and how there are a lot of sex-differences in that disease as well. I feel like this paper had so many different points that could be talked about, so I’m going to stop there for now.

The Burrows paper was also interesting. It was really cool to see the effects of environmental enrichment on the schizophrenic like behavior of the mGlu5 model. It’s really exciting to think that EE along with therapeutics could lead to better outcomes, and maybe even work as a preventative treatment. I was convinced of this paper’s results, although I wish they had given more information on the validity of the mGlu5 KO as a model for schizophrenia. Yes they saw memory and spatial learning deficits and PPI loss, but this paper seemed to kind of skim over these ideas more so than the other papers. I’m sure there’s probably another paper out there specifying the validity of this model. As of right now, I feel a little overwhelmed by the complexity of schizophrenia. First we saw dysregulation in dopamine, now in NMDA and glutamate. I wish I knew a little bit more about the basics of schizophrenia before reading these so I could better understand the thought process behind these experiments.