Skip to main content

Schizophrenia, Ayhan & Burrows

By

The papers by Ayhan et al and Burrows et al focused on mouse models of schizophrenia and possible mechanisms that underlie its pathology. I really appreciate that both of these papers included female and male mice in their studies since schizophrenia in humans does not seem to be sex-specific. Ayhan et al focused on the effects of the mutant human DISC1 gene (hDISC1) seen in schizophrenic patients, whereas Burrows et al mainly studied the role of metabotropic glutamate receptor 5 (mGlu5) in schizophrenia.

The Ayhan paper immediately makes me think of the long-standing debate of “nature vs. nurture.” Their data indicate that different effects on both neuroanatomy and behavior depending on when the hDISC1 protein is expressed. This is especially relevant in light of the discovery of epigenetics, where some genes can preferentially express in individuals depending on their experiences. Therefore, I am interested to know how environmental factors, such as maternal care and absolute “mouse poverty” could affect those specifically with the hDISC1 gene. Are the same behavioral effects seen in hDISC1 mutants with enriched upbringings the same as those seen in hDISC1 mutants brought up under adverse conditions? In my opinion, that would make their study much more translatable to humans, especially to the groups who are identified to have the DISC1 gene mutation, since human upbringings can substantially affect one’s health in adulthood. Additionally, if no significant effects were seen in the experiments testing environmental factors, it would strengthen the Ayhan paper’s argument that hDISC1 expression itself causes the effects seen in schizophrenia. I acknowledge that this is much easier said than done.

The Burrows paper addresses the possibility of environmental factors contributing to schizophrenia and its associated symptoms. However, they identify mGlu5 as a mediator of behavioral impairments seen in schizophrenia. These results, along with the results from the Ayhan paper, highlight the complexity of schizophrenia as a neurological disorder. I would be very interested to see how environmental enrichment from the Burrows paper affected the hDISC1 mice from the Ayhan paper. Can environmental enrichment truly act as a therapeutic treatment for schizophrenia and counteract the effects of genetic mutations? Or are these beneficial effects of enrichment only sufficient when symptoms of schizophrenia are induced by dysregulation of NMDAR’s?

The Ayhan and Burrows papers certainly elucidate possible causes that underlie the pathology of schizophrenia. I think it’s extremely important for readers to critically think about the results regarding such complex disorders so that neither genetic nor environmental factors are discounted as possible contributors to the symptoms of schizophrenia. As always, more research is needed to paint a clearer picture of schizophrenia as a human disorder.

Comments

Post a Comment

Popular posts from this blog

Week 2- Dopamine Modulation of Depressive-like Behaviors

By
The Chaudhury et al paper explored the neural circuit mechanisms involved in the dopamine modulation of certain symptoms of depression. In this study, the researchers looked at social interaction and sucrose preference as part of their social-defeat paradigm, which has been shown in the past to be indicative of depressive-like behaviors. Although I initially did not completely see the connection between the social-defeat stress model of depression and the tonic vs phasic firing of dopamine neurons, it seemed that susceptibility and resilience to stress played a role in the functional/behavioral effects of dopamine firing. It was interesting to see how chronic mild stress with phasic firing of VTA dopamine neurons converted even resilient mice into susceptible mice.  The Tye et al paper similarly looked at the dopamine modulation of depressive-like behaviors, focusing on motivation with the forced swim tests and open field tests, followed by measurement of anhedonia by quantifyi...
Post a Comment
Read more

Sial & Allsop

By
Sial et al. derived a novel approach for studying what they deem vicarious defeat stress (VSDS) as a model for MDD, PTSD, and other mood-related disorders as an alternative to the classical CSDS paradigm. Using adult male mice, they demonstrate that their model induces a robust and measurable social avoidant phenotype as well as other stress and anxiety related behavioral outputs. Their subsequent rescue study with chronic fluoxetine treatment shows reversal of the behavioral phenotypes and emphasizes the predictive validity of the model. Allsop et al. found that BLA-projecting ACC neurons preferentially encode socially derived aversive cue information by encoding the demonstrator’s distress response during observational learning, hence enabling acquisition of negative valence of cue by BLA neurons and behavioral output. In order to test their hypothesis, Allsop et al. used an observational fear conditional paradigm to create association between a conditioned stimulu...
Post a Comment
Read more

Buffington and Reber

By
Buffington et al. explore a mechanism by which maternal obesity can induce neuronal and subsequent behavioral disorders. Using a model of high-fat diet (MHFD)-induced obesity, the authors showcase the strong connection between the brain and the gut, and its impact on behavior. The findings are provocative; by exposing these offspring to the microbiome of control offspring, there was evidence of a rescued observed behavioral phenotype. Furthermore, a phylogenetic profiling of the gut microbiome revealed a decrease in L. reuteri within MHFD offspring, and introduction of live L. reuteri into the drinking water shows successful rescue of the behavioral issues in the MHFD offspring. L. reuteri-induced expression of oxytocin within the paraventricular nuclei of the hypothalamus provides a potential mechanistic explanation for the behavioral changes. I thought this paper provided robust support for the hypothesized interaction between the gut biome and the developing CNS, with tremendous po...
Post a Comment
Read more