Moore et. al. & Kellendonk et. al.

This week’s papers addressed schizophrenia, a disease we have not discussed previously. Both of these papers went about researching schizophrenia in different ways. Antipsychotics are known to relieve positive schizophrenic symptoms by down regulating the D2 receptors. Taking this into account, Kellendonk et. al. worked backwards and upregulated D2 receptors in the striatum. After doing this, they observed if over expression of D2 receptors caused deficits in working memory and cognition. In a different method, Moore et. al. created a model of schizophrenia by injecting MAM into damns during embryonic development. They then ran many tests (including histology, neurophysiology, and behavioral tests) with adult offspring to determine if this model can be used as a model of schizophrenia.

After showing that the transgene is successfully over expressing the D2 receptor, Kellendonk et. al conduct delay non-match to samples in which mice learn to associate a certain arm in a maze with food, and then after a delay, must learn to reverse the previous association. It was then recorded how long it took for the mice to learn the reversal. The D2R mice show a deficit in working memory when compared to the controls. I thought the most interesting part of this paper was Figure 5, in which the D2R transgene was turned off 90 days after birth. The D2R and control mice were then tested with the DNMTS task, and the D2R mice showed deficient working memory even when the transgene was off. This is demonstrated even further in C, in which they turned transgene expression off at birth. The D2R mice still showed a deficit in working memory, showing that there is a developmental aspect of the over expression of D2 receptors, enough that there are still lasting effects even when expression is turned off. I also thought it was interesting in Figure 6 when they looked overexpression of D2R in striatum and D1 receptors in the PFC, and tried to make inferences between PFC/striatum projections and working memory. I think that further studies could be conducted, solely focusing on the overexpressing D2 in striatum/working memory in PFC connection because in the paper they address the “U” effect of D1 receptors but are vague about the effect up or down regulation of these receptors.

The main point of Moore’s paper was to prove the validity of the MAM-E17 rat for modeling schizophrenia. I was pretty convinced after reading this paper. As the figures show similarities between the model in schizophrenia morphologically, neurphysiologically, and behaviorally. I found the results Figure 10 particularly intriguing, in which they looked at the effect of PCP on ambulation distance in prepubertal vs adult mice. Moore et. al. found that the symptom enhancing effects of PCP only occurred in E17 mice after puberty, phenomenon that is also found in schizophrenia.

I found these papers thought provoking, and opened my eyes to the heavy developmental aspect of schizophrenia, something I was not previously aware of. I would be interested in reading more research on the developmental aspects of schizophrenia and what exactly causes the schizophrenia symptoms to start appearing. I think that if we can understand the developmental aspects of schizophrenia more clearly, it could lead treatment preventing or reducing the introduction of schizophrenic symptoms during adulthood.