Ayhen et al. (2011) and Burrows et al. (2015)

The Burrows et al. (2015) paper, in my opinion, made a very interesting breakthrough with regards to the effect of environmental enrichment (EE) on the mGlu5 and NMDAR pathways.  They tested the glutamate hypothesis of schizophrenia, unlike Ayhan et al. (2011) who tested the dopamine hypothesis of schizophrenia. 

In the Burrows et al. (2015) paper, the researchers investigated the consequences of an mGlu5 gene knockout (KO) with and without EE.  They found overall behavioral defects in mice with the knockout but also discovered that mice that underwent EE treatment displayed an alleviation of these defects. The last figure in their paper presented the most interesting aspect of it: that the hindering effects of MK-801 are not lessened by the presence of EE but strengthened by it.  I found that they stated their case very clearly through this paper, especially with how they presented their data.  However, I wish that they had included their data regarding the levels of BDNF proteins in the hippocampus of mice.  In the supplementary information, they add that EE increased BDNF proteins in WT mice but not in KO mice, which suggests the mGlu5 might be necessary for the presence of BDNF in the hippocampus.  This paper encourages scientists to further research mechanisms of treatment via glutamate receptors.

In the Ayhan et al. (2011) paper, the authors test the effects of mutating the Disrupted-In-Schizophrenia-1 (DISC1) gene at different stages of development.  These testing groups included mice that expressed the mutant DISC1 (hDISC1) during either the prenatal period, postnatal period, or both periods.  The pre-post group exhibited higher levels of depression, aggression, and psychosis when DISC1 was mutated.  For some reason, females showed significantly higher immobility during the forced swim test (FST) when hDISC1 was induced in the postnatal period.  These behavioral differences reveal the additive effects of hDISC1.  They also point to possible sex differences in the behavioral reactions to hDISC1 that could be applicable to schizophrenia.  This paper was interesting because it showed the different phenotypic effects of DISC1 mutations in different developmental stages.  However, I did not like this paper as much because the researchers presented confusing morphological figures and bar graphs.  Even though I know that “no results” are still important results, these figures did not seem necessary because they did not correlate very well to the graphs.  All in all, the Ayhen et al. (2011) paper further supports the dopamine hypothesis of schizophrenia.  After reading these two papers, I think that treating schizophrenia through both the glutamate and dopamine pathways of the brain is necessary.