Ayhan et al and Burrows et al

The papers read for this week, both Burrows et al and Ayhan et al studied schizophrenia models.  Both papers were very clear in their manner of presenting background information and going through their specific experimentation and results. 

Ayhan et al wanted to study the effects of mutants DISC1 on neurodevelopment at different times since the effects of it prenatally hadn’t been studied previously.  Expressing mutant hDISC1 was achieved by regulating the consumption of DOX containing food.  They had 4 different groups, one without mutant DISC1, prenatal, postnatal and the prenatal+postnatal. Their main conclusion was that mutant hDISC1 results in very different effects quantitatively and qualitatively depending on when in their life it was expressed.

This is the first paper I think I have read where the groups consist of both female and male mice and in fact these showed differing results. For example, post female mice spent significantly more time immobile in the behavioral tests while the male didn’t show any effects.  I am not really sure why this is but I might think it has to do with hormonal changes since it is common for females to experiences depressive like behavior during hormonal imbalances.  However, I can’t make sense of the fact that MK801 injections resulted in total locomotor activity in the male of pre-post but no difference was observed in the female groups. Ayhan et al weren’t able to truly explain these gender specific results with all of the imaging and specific brain details they gathered.  I am really interested in knowing more about this. I have seen that other studies show that women have later onset of schizophrenia and believe this is due to estrogen.  Therefore, I think it would be interesting to continue this study but incorporating the alterations of hormones and maybe even injecting estrogen to the male mice and see how these behavioral test results are affected.

            Burrows et al focused on the gene-environment interactions and its role on schizophrenia. This paper was recently published, and is following previous research they published in 2011.   The experiment wanted to study the effects of Environmentally Enrichment on behavioral endophenotypes in regard to schizophrenic mice lacking mGlu5.   Moreover, the role of NMDAR wasn’t clear either. I really enjoy the studies combining genes and environment since I am true believer of the fact that the environment has effects on the genetic issues.  I was very impressed with the therapeutic effects the environmentally enriched household had on mice.   This has been shown to be reduced by drugs such as clozapine which increase NMDAR binding.  Therefore, this has a lot of human applications since one can truly find similar therapeutic alterations that might be accompanied by small drugs dosage in order to alleviate the psychotic behavior of schizophrenic patients. I was impressed by the fact that EE was able to reduce locomotor activity in WT mice, it seems to me that it has some sort of like meditation effects.  I am very interested in understanding why EE was able to relieve the long term memory loss but no the short term.  One of their most important findings was the fact that NMDAR can be modulated by mGLU5 and from here I think they have a very strong base upon which to  keep expanding their studies. I really liked both papers a lot, however I think I liked this one more just because it included the environment interventions as therapeutic effects.