Skip to main content

Ayhan and Burrows

By
In their paper, Ayhan et al. (2011) discuss the importance timing plays in the expression of the protein hDISC1 during neurodevelopment, and how this contributes to the manifestation (or lack thereof) of Schizophrenia-like phenotypes. Burrows et al. (2015) explore the role of environmental enrichment in mGlu5 KO mice, and discover robust effects in restoration of spatial learning as well as amelioration of Schizophrenia-like behavioral phenotypes.
There are a few things I found notably interesting in both papers. In Burrows et al., there were no sex differences seen within the experimental group. On the other hand, Ayhan et al. reported sex-specific effects of mutant hDISC1 both in behaviorally and neurally. I thought this brought up an interesting point regarding the etiology and sex-specific nature of Schizophrenia, and whether the sex differences can be more attributed to temporal expression of protein as opposed to gene-environment interactions, or whether this is presumptous or simply incorrect. I would be curious to see a follow-up study by Ayhan et al. where they further explore these behavioral sex-differences in the mutant hDISC1 what that could mean on a more translational level.

I particularly enjoyed the developmental aspect of the Ayhan et al. paper. Although early onset Schizophrenia is not typical among children or adolescents, the aberrant developmental trajectory of the brain is established during gestation, long before clinical symptoms of the disease appear in early adult life. It brought me to thinking about the environmental enrichment model in Burrows et al., and whether we need to start directing more of our focus to exploring early intervention models for major psychiatric disorders like Schizophrenia. I believe a comprehensive characterization model of hDISC1 throughout pre and postnatal development into adolescence and adulthood would be a start, and then creating novel environment enrichment behavioral assays based on these differential patterns of expression. In either case, there is still a tremendous amount of research that would need to be done, but I certainly see a future clinical application for (time and maybe even sex-specific) catered enrichment intervention models.

Comments

Post a Comment

Popular posts from this blog

Gut-Brain Interactions: Buffington et al, Reber et al 2016

By
April 13 Papers (Buffington et. al, Reber et. al) I found this week’s papers to be quite novel in that they both proposed potential treatments for neurodevelopmental or psychiatric disorders that target bacterial or microbial abnormalities and how these give rise to certain behavioral and physical symptoms associated with the disorders. I thought this was a very unusual yet interesting approach, and as I have not previously studied the gut-brain axis, these papers offered me a fresh perspective on researching psychiatric and neurodevelopmental disorders. They were also unconventional in their focus of the physical symptoms that often accompany mental disorders, as this is not something that I have seen many other papers touch upon very much. Particularly, I was surprised by the Reber et al paper’s focus on the link between psychiatric disorders and inflammation in organs other than the brain, such as the colon, and the Buffington et al paper’s description of a relationship between ...
Post a Comment
Read more

Gut-brain axis

By
This weeks papers Reber et al. 2016 and Buffington et al. 2016 present a super interesting look into the gut-brain axis. Regarding both of these papers, it was amazing to see how potent favorable or unfavorable gut microbiome compositions are in affecting neuronal signaling and overall behavior. Reber et al. shows how immunoregulatory immunization with specifically heat killed M.vaccae can serve as a protective factor against chronic subordinate stress induce colotis as well as behavioral symptoms due to chronic stress as such. Interestringly, this paper depleted regulatory T cell activity via the anti CD25 antibody in order to show that the antiinflammatory mechanism induced by m vaccae immunization is depented on the secondary regulatory mechanisms offered by Treg proliferation and signaling. But, when T reg signaling was removed, this did not seem to cause a significant change in behavior . Therefore, this begs the consideration of what othe rmechanisms may be at play in order ...
Post a Comment
Read more

Ramirez et al.: 2013 and 2015 Papers

By
In these papers, Ramirez et al. strive to understand how memory encoding via optogenetic manipulation of engram-bearing cells in the hippocampus, specifically the dentate gyrus, can affect an animal’s response to a stressful context.  The first paper, published in 2013, was crucial to the field as it introduced this very exciting technique; in this paper, Ramirez et al. use tet-tag to manipulate brain circuity and establish associations between two contexts. Throughout the paper, this is referred to as “false memories.” Using these artificial memories, the investigators are able to manipulate the animal’s fear response in a specific context. Specifically, after the animals are conditioned to a repeated fearful stimulus (a foot shock, in context B), activation of the involved DG cells in a different context (context A’) will also initiate a fear response (in absence of any foot shock). In this experiment, the false memory is used to create an unnatural fear association in a given...
Post a Comment
Read more