Mouse models of schizophrenia


This week we take a look at two articles form early 2006 focused on animal models of schizophrenia. Each of the articles develops and tests a distinct mouse model for schizophrenia. Importantly, both of these models are especially focused on the cognitive symptoms of schizophrenia, which other models do not present and which are not primarily targeted by current treatment in humans. 

In the article by Moore and colleagues (2006), the model is achieved by disrupting embryonic development of paralimbic frontal and temporal cortices, while in the article by Kellendonk and colleagues (2006) the model is achieved by overexpressing D2 receptors in the striatum. Results in cognitive tasks are not unlike in the two models, which highlights the fact the schizophrenia might be better conceptualized as a heterogeneous disease in which different neurobiological substrates given origin to similar symptoms across individuals. This means that not one model might be truer to the human disorder than the other, but they might better reflect the nature of the disorder to different degrees in different individuals. Another important result from both studies were the findings that there is a critical period during embryonic development during which dysfunction can result in schizophrenic like symptoms. Here, the two articles agree very closely on the time-frame for this dysfunction in mice – the Moore et. al (2006) found that MAM should disrupt development at week 17 and Kellendonk et. al (2006) found that the overexpression of D2 receptors in the striatum of transgenic occurs during week 17 as well. While this highlights the relevance of neurodevelopmental disruption in schizophrenia, these models fail to account for why the disorder appears in some individuals and not other. This is common across many animal models, where a targeted disruption result sin deficit in all individuals, which rarely is the case in humans, where identical twins might not both develop a disorder due to environmental factors. 

In conclusion, here two animal models for some symptoms of schizophrenia are presented. While they might not be ideal to inform on the disease as a whole, they can very well inform about different neural substrates that are likely be behind some of the symptoms of schizophrenia observed in humans.

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