Week 7

There are so many things to say about these papers, especially the Ayhan et al, but I will try to be brief. To start with the Burrows et Al paper, I found it underwhelming in terms of results, but I do not think that is by fault of experimental design but rather a function that the diverse effects of mGlu5 on the endophenotype of schizophrenia. I initially had my doubts that the results would indicate that mGlu5 KOs are a model of schizophrenia in mice based on the seemingly opposite effects mGlu5 stated in the Introduction. I was confused that treatment that the mGlu5 antagonists augment hyperlocomotive effects of PCP and MK-801 while a mGlu5 KO show a baseline hyperactivity, and put a note to myself to think about this going thru the paper. However, getting to the results did not help my confusion but only amplified it. I’m troubled that there is significant cross over between the results of EE seen for both the KO’s and WT’s, which to me indicate that the EE isn’t helping the KO’s compensate but rather overall provides “beneficial” neuroplasticity changes to the brain. This is indicated by the GluN2A, locomotion, and escape latencies data. While on the other hand there are some KO specific effects of EE, the data as a whole does not lead me to develop any concrete conclusions about mGlu5 KOs. The NMDA receptor antagonist data did not help me clarify an opinion – it seems as though EE helps ameliorate some of the effects of an mGlu5 KO except when a schizophrenic phenotype is induced through the NMDA antagonists, where it instead served to exacerbate schizophrenic-like symptoms. Perhaps the data as a whole just show the complexity of the NMDARs, environment, and mGlu5, but the lack of clarity in regards to mGlu5’s effects in the data disallowed me from drawing any concrete conclusions about the data presented.

            To move on to the Ayhan et al paper, which I found incredibly thorough, I was able to draw more concrete conclusions from the data presented. Specifically, I thought this paper demonstrated a clear influence of the “pre+post” activation of the hDISC-1 gene, but also some interesting caveats to that point in regards to neurobiological developments. It seems as though most of the “behavioral” effects of the hDISC-1 mutant occur based on post activation, whereas a lot of the morphological and neurobiological effects are seen regardless of when the gene is activated. This is super interesting, because it somewhat correlates what we know about schizophrenia in humans. Additionally, the gender-specific effects of the hDISC-1 gene shine some light on how concurrent endogenous differences in brain structure and development between genders may influence how schizophrenia develops differently between males and females. Overall, I loved this paper. I found it so incredibly thorough, and I loved the data they found (I’m sure they did too!).