Week 6: Kellendonk and Moore

I was really excited to read this week’s papers because schizophrenia is something that has always fascinated me, and I was curious to see how scientists could mimic schizophrenia in mice. The supplemental data of the Kellendonk et. al paper did a great job answering my questions about the behavioral protocols used to measure schizophrenic symptoms. Many of the paradigms used were those used to test anxiety and depression, while a few others were completely new to me. However, I am not entirely convinced that this animal model is close enough to a successful representation of schizophrenia. Unlike depression models which can capture symptoms such as anhedonia and anxiety, it is impossible to definitely induce certain schizophrenic symptoms in animals, such as hearing voices and paranoia. I kept this thought in mind throughout my entire reading, and it was nice to see the researchers address this concern and admit that their model was imperfect by the time the discussion section rolled around.  Despite this, I enjoyed the clarity of this paper and how easy it was to follow. Almost all my BNS classes have mentioned the importance of dopamine regulation in schizophrenia, and it was nice to see researchers narrow in on D2 receptors in the striatum. Their conclusion about an increase in D1 receptors actually being responsible for the working memory deficits due to the increased density of D2 receptors in the striatum was decently supported, and I would love to see if this was pursued and investigated further.

The Moore et. al paper approached schizophrenia differently, by using the methylating agent MAM on embryonic day 17 in rats. The coolest part of this research to me was the noticeable difference between administering MAM on day 15 vs. day 17. This also raised some questions about how this could translate to a human model. Although I don’t know much about schizophrenia, I tend to think it is something that develops over time, either due to childhood trauma or due to something that happens during puberty. Although the MAM injection did induce schizophrenic symptoms in the rats, it does not prove that something like this can naturally occur in humans during pregnancy. After reading both these papers, I would like to see if schizophrenic symptoms could be induced in rodents by mimicking some sort of early life trauma, or something more natural along those lines. While overexpressing D2 receptors or silencing certain genes with MAM are both interesting methods, they don’t answer the question of why these things may happen to people and what can be done to prevent it.