Skip to main content

Modeling Schizophrenia: Ayhan et al. and Burrows et al.

By
Both of these papers aimed to model schizophrenia in mice models, albeit by very different avenues. The first paper, published in 2011 by Ayhan et al., investigated the role of mutant human DISC1 gene in neurobehavioral abnormalities associated with the disorder by examining the effect of the mutant hDISC1 expression at different timepoints of development. Across these developmental stages of mutant expression, the researchers tested social interaction, depressive-like behaviors, and drug-induced activity. 
I very much appreciated that this paper used both male and female mouse models (which is surprising for a 2011 paper, I think). However, for multiple behavioral tests, the groups of male and female mice exhibited different behaviors, and for some reason this was not addressed in the paper. Specifically, female mice in the “post” group spent more time in immobility compared to the female mice in the “no” group, but “expression of mutant hDISC1 had no effect on these behaviors in male mice of either group.” Also, the male mice in the “pre + post” group exhibited an increase in locomotion with injections of MK-801 and d-amphetamine, but there was no difference among the groups of female mice. Is this not significant? Perhaps I am missing something here, but I would expect an explanation, at the very least, for why the results were different for the male and female mice. Moreover, I found the data from the frontal cortex of the male mice (specifically the decrease in tissue content of DA and DOPAC in the experimental groups when compared to the control) very convincing, but what about the frontal cortex in females? I could not even find this in supplementary. All in all, I did find the data in this paper compelling, but I would have liked an explanation for why the behavioral effects of the mutation were not consistent across the male and female mice.
The second paper, published in 2015 by Burrows et al., used an mGlu5r deficient-model to investigate the interactions between genes and the environment in the context of the development of a schizophrenia phenotype. I believe that this is a very important aspect of all neurological disorders that must be addressed; however, I was shocked to find that their study used only male mice. I feel that it would have been interesting to assess the differential effects of environmental enrichment on male and female mice – can’t we agree that there is possibly a difference in the way that genetics in males and females are modulated by the environment? I would have been much more convinced if this had been addressed in the paper. 

Comments

Post a Comment

Popular posts from this blog

Buffington et al (2016) and Reber et al. (2016)

By
This week's articles were about the role of the gut-brain axis in neurodevelopment and stress. Reber and colleagues used a heat-killed version of the bacteria, M. vaccae, as a type of vaccine and found that administration to mouse models resulted in decreased response to chronic stress, prevented colitis related to stress, and reduced measures of anxiety. Reber et al. also used the inactivated M. vaccae in a mouse model of IBD and found that the bacteria prevented stress-induce flare-ups of colitis, but that this could be reversed by removing T cells. Buffington and colleagues instead examined the role of gut microbiota in maternal high-fat diets (MHFD) in the neurodevelopment and social behaviors of their offspring. Buffington et al. found that housing MHFD rats with the offspring of regular diet (MRD) rats prevented social deficits in their offspring. They also found that this co-housing arrangement prevented an imbalance in the gut bacteria Reber and colleagues' findings w...
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

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