Week 6

This week, both papers, released in the same year, focused around producing rodent models of schizophrenia. Both recognized a developmental dysregulation inherent in the formation of the disease, albeit via different mechanisms. Kellendonk et al. found overexpression of D2 receptors in the transgenic mouse striatum to be sufficient to induce schizophrenic symptomology such as deficits to working memory, and physically induce changes to D1 transmission in the prefrontal cortex which may be related to the cognitive effects seen in the model. However, Moore et al. studied disruption of embryonic brain development in mice using methylazoxymethanol acetate (MAM) and its usage in producing a schizophrenic model. In their study, Moore et al. found that MAM resulted in general microencephaly and greater deficits to motion, executive control, and prepulse inhibition, and while there were selective decreases in cortical thickness in later exposure of MAM, early of exposure led to general microencephaly.

            Ultimately, this week’s discussion revolves around the question of a preference between two models of schizophrenia and whether one study provides a more thorough argument. At first, Kellendonk appeared to be a more convincing paper as it directly studied dopamine which has been classically associated with schizophrenia. As well, alterations to D2R specifically in the striatum would theoretically have an effect on the output of the corticostriatal pathway which may be reflected in the alterations in D1 activity in the PFC which may be cause of typical schizophrenia symptoms. Another interesting aspect uncovered in this study was the irreversibility of effects of developmental overexpression of D2R, if not greater severity induced by such an attempt at regulation. While I was initially skeptical of Moore et al.’s findings as it seemed more blunt in its focus on premature pharmacological cessation of cortical development without focus on neurotransmitter activity, their correlates between former findings in schizophrenia and findings in their own study were convincing at least from a neurological standpoint, and their use of orbitofacial activity measures was if nothing else novel and interesting. Ideally these two models could be combined, possibly with a more specific focus on cell identity in the Moore-style model.