Week 6 Articles

I was caught in mixed feelings after reading both of this weeks papers.  Moore employed the use of methylazoxymethanol, a neurotoxin, to model symptoms of schizophrenia, while Kellendonk focused on manipulating an over expression of D2 receptors in the striatum.  The use of MAM to induce schizophrenia like morphological changes and behavioral pathologies seems a little rudimentary in approaching an animal model of the disorder.  Although the following studies revealed a wide scope of observations, including morphologically relevant discrepancies from a control, the context specific impacts seemed to be too selective to warrant a more generalized application to schizophrenia.  A strong point of the Moore paper however, was the focus on E15 versus E17 stages of MAM administration and the subsequent differences in schizophrenia related effects.  This both showed that schizophrenia does have roots in developmental stages and exposed MAM to have a temporal dependency as a mimicking agent of the disorder.  This type of limitation is crucial to understanding the extent of which a single variable is in constant battle with confounding variables when under going such testing.

The Kellendonk paper sat a little better with me as I felt they confronted their limitations head on and made sure to convey their results very honestly and in light of their shortcomings.  Their pursuit to me also seemed more reasonable, a focus specifically on the cognitive symptoms due to up regulation of receptors as opposed to the broad-spectrum approach Moore took. Regarding their actual results, it was clear that D2 receptor up regulation in the striatum impacted dopamine levels and more specifically dopamine turnover rates in the prefrontal cortex.  There were observed impairments in working memory tasks and other behavioral tests but none that relied on continued expression of the excess receptor, which brought back the significance of a critical developmental window in the manifestation of the disorder.  By the end of the Kellendonk paper, I was convinced that the striatum D2 receptor to prefrontal cortex D1 receptors relationship deserved more experimentation in creating a working animal model of schizophrenia.