moore and kellendonk

The two articles this week used very different methods to model the symptoms and pathology of schizophrenia. The Moore et al paper focused on affecting the development of rat brains in order to obtain a model of schizophrenia that accurately reflected the symptoms displayed in patients, without severely altering cognitive function. The MAM E-17 model produced a significant decrease in the gray matter of the cortex and thalamus, and produced orofacial dyskinesias/perseveration that is consistent with the symptoms of schizophrenia. This paper sheds a great deal of light on the possibility that many of the symptoms associated with schizophrenia may be due to developmental issues before birth, as well as reduction in cortical gray matter and and increase in neuronal density.

The Kellendonk article focused more of its attention on the dopamine D2 receptors that are known to be linked to some of the symptoms of schizophrenia, in particular the positive symptoms. By overexpressing D2 receptors using transgenic mice, certain cognitive deficits could be measured, such as working memory and cognitive flexibility. The most interesting aspect of this article, to me, was that even when switching off the D2R transgene at birth the cognitive deficits were still seen. This implies that simply overexpressing the D2 receptors during development was sufficient to cause significant cognitive impairment in behavioral tasks, such as the DNMTS T-maze task. It was also interesting to me that they were able to prove a link between D2 overexpression in the striatum and D1 receptor activation in the prefrontal cortex.

Overall, I think that the Kellendonk article had more application for the future, in that it addressed some of the symptoms of schizophrenia caused by D2 overexpression (cognitive inflexibility and working memory deficits) and the potential causes for them. Although there are antipsychotic drugs that antagonize D2 receptors, these drugs generally only diminish the positive symptoms of schizophrenia, and this paper showed the symptoms of schizophrenia that are left untreated using typical antipsychotics, and potential causes of them.