Different Rodent Models of Schizophrenia - Annissa DeSilva


The papers this week focus on creating relevant models for schizophrenia. Kellendonk et al . produced a mouse model using transgenic means that had over expression of the D2 receptor in the striatum, this was relevant due to the notion that most effective anti-psychotics (treating positive symptoms) are D2 receptor antagonists. Moore et al. created a developmental animal model by injecting the methylation agent methylazoxymethanol acetate (MAM) into dams on E17 which produced mice with abnormal development of the frontal and limbic cortical circuits and and abnormal dopamine (DA) input to the striatum. I thought Moore et al’s findings were very interesting especially the inclusion of cerebral cortex abnormalities which are absent from other models of schizophrenia such as the neonatal hippocampal lesion model and the chronic phencyclidine model. The inclusion of this symptom seems very significant because as seen in the study and in those with schizophrenia, a decrease in cortical thickness is evident. Cortical thickness relates to and includes the projections (terminals and dendrites) of neurons, thus the inclusion of the decreased thickness may play a key role in understanding how to treat the cognitive deficits (and other potential negative symptoms) that arise with this disorder. The MAM-E17 model seems to incorporate the already presenting symptoms in other models with additional anatomical features which may be implicated in lack of cognitive ability. When looking into other rodent models of schizophrenia, it seems that most only address positive symptoms related to schizophrenia, not negative ones. Thus, I think the development of the MAM-E17 model is necessary and could aid pharmacological development of antipsychotics especially considering that both classes of antipsychotics are mainly effective for positive symptoms. However, I feel as if Moore et al. left out one important measure for schizophrenia: ventricular enlargement. Other studies using the MAM model have noted that MAM does not produce a significant ventricular enlargement. It is not a requirement for every model to exhibit every symptom, however I find it noteworthy because there is consistent data to suggest that ventricular enlargement is a hallmark morphological aspect of schizophrenia and Moore et al put a lot of emphasis on the nuances of the schizophrenic neuroanatomy of the brain of their model.
Overall, I think the development of new animal models of schizophrenia are significant for the discovery of new anti-psychotics and potentially uncovering the etiology of the disorder. However, I do find it hard to completely asses the validity of each model due to the fact that neither study used anti-psychotics as a control to further support their model (as we saw last week Sial et al used anti-depressants effects to further support their model of emotional stress). As mentioned previously anti-psychotics are not effective in treating negative symptoms, which are produced in both models, so it is understandable why that was left out. Perhaps If a more efficient drug that effectively treats the positive and negative symptoms of schizophrenia is developed, we will see an emergence of “standard schizophrenia” mouse models out of the many we have currently.

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