Sunday, October 30, 2016

10/31 Moore et al. and Kellendock et al.

            Moore et al. administered MAM to pregnant rat dams. This model exhibited a neuropathology similar to that of schizophrenia, along with cognitive inflexibility and sensorimotor gating deficits, when the MAM was administered on E17. Previously, most work done with a MAM model of schizophrenia involved administering the drug on E15. They believe that the E17 model is better model of schizophrenia since there are less unrelated side effects, like microcephaly and motor impairments, when it is administered on E17 rather than E15.
I was curious about how E17 was chosen. I would be curious to see the results of their tests on other days, like E16 or E18. MAM-E17 brains were still about 7% smaller than control brains, so maybe administering it on E18 would have less of an effect on overall brain size.
            In the reversal learning task, the methods stated that females were used as controls. It didn’t seem like there were females used at any other time in the paper, so this may affect the results of the task. I would also like to see if they get the same results from using the MAM-E17 model on females. Also, the authors are unsure of how MAM preferentially affects cortical neurons. If more were known about how this model works, the model would be more convincing to me.

            Kellendock et al. used a transgenic mouse model of schizophrenia that overexpressed D2 receptors using a tetracycline transactivator (tTA). This expression was limited to the striatum. Overexpression of DA did not cause more locomotor activity, deficits in sensorimotor gating, or increased anxiety compared to control mice. In an attentional set-shifting task, DA overexpression mice had increased latency to choose between odors during reversal trials. This corresponds to executive function impairment in schizophrenia. The transgenic mice were tested in a DNMTS maze task off and on dox. The cognitive deficits remained even when the mice were put on dox so the DA receptor overexpression gene was turned off. The authors also found increased D1 expression in the mPFC, which is involved in executive function. They believe that the cognitive deficits are due to an imbalance in D1 activation in the mPFC. There is evidence that striatal dysfunction affects the PFC, so more research could be done on this pathway in the future. Since there are differences in circuits between rodents and humans, it is difficult for the rodent research to be translational. However, rodent models can still be used to test single aspects of schizophrenia. In the future, more research could be done on the additional cognitive deficits of schizophrenia.

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