Examining schizophrenia modeling in mice - John Lambert

            The papers this week both focused on animal models of schizophrenia, a rather uniquely challenging mental illness. Kellendork et al. investigated the link between overactive dopamine function and schizophrenia-like behaviors and changes in mice. Moore et al. took an extremely different approach by specifically targeting specific cortical development in rat embryos. Despite both papers’ similarity and the fact that they were published the same year, they have very different styles. I assume this was due to some combination of different journal expectations and differing backgrounds of the authors, but it was interesting to notice. Both papers found task deficits in working memory and behavioral flexibility, which are commonly found in human schizophrenia patients. 
           Kellendork et al. began with a dopamine hypothesis of schizophrenia, and cited previous work that examined the striatum and the mPFC. To look at this, they modulated the expression of D2 receptors (D2Rs) in the striatum of transgenic mice. They found that overexpression directly impacted receptor binding, cortical activity, and task performance. Kellendork et al. frequently tied together their rational and findings with clinical data, which was actually quite helpful since I am not as familiar with the neurophysiology and behavior observed in schizophrenia as I am with other mental illnesses. As part of their controls, they turned off the transgenic expression of D2R with doxycycline; something that Moore et al. was unfortunately unable to also do. Their downstream findings, which implicated D1, must have been replicated and investigated in the past 13 years, I’m interested in the current research on that. 
            Moore et al. used MAM at E17 to alter brain development in rats, inducing schizophrenia-like brain structure changes and task deficits in those same rats at adulthood. It is incredible the difference between MAM administration on E15 and E17 and normal rats, and how well MAM administration on E17 specifically induced later life schizophrenia models. One of my roommates asked what I was reading this morning and he laughed for a while about the fact that someone’s job was to give schizophrenic rats PCP (never forget neuroscience experiments sound weird at times!). I didn't expect these methods or results, but I found both to be very interesting. This paper’s new (circa 2006) model for schizophrenia and their findings definitely are noteworthy. Similar to Kellendork et al., I am interested in the more recent findings that have stemmed from this paper, especially in regards to embryonic development and drug discovery. 

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