Gene expression in models of schizophrenia


This week we looked at two papers focused on how changes in gene expression influence the phenotype expressed in two genetic models of schizophrenia. The first paper (Ayhan et. al, 2011) focuses on the DISC1 model of schizophrenia, and looks at differential expression of the mutated gene over different stages of development. This study showed that expression of the DISC1 gene during specific periods (i.e. pre or post-natal) is critical for certain changes to take place. Interestingly, results also showed that some alterations require expression of the gene to occur exclusively during either the pre-natal or the post-natal phase. Such a result reveals how the expression of this gene will not only have differing effects depending on when it is expressed, but that expression at a certain time can influence the phenotype resulting from expression at another, different time.
                The second study, by Burrows and colleagues (2015) also looked at altered gene expression in a model of schizophrenia, albeit indirectly, but looking at the environmental effects observed in the GluM5 knockout model. In this study, it was observed that the environment had a significant effect on the phenotype expressed by the same genotypical model of schizophrenia. Furthermore, the results also showed that the same environment can have different a different impact on the phenotype expressed depending on the genotype. Together, these results highlight the impact the environment has on behavioral phenotypes, specifically those related to schizophrenia. Furthermore, these results also bring attention to the fact that there is not one single ideal environment that can ameliorate or avoid the onset of schizophrenia like symptoms, as gene-environment interactions are complex, and the same environment can have beneficial or detrimental effects on the animal. Finally, these results suggest that the environment has some level of influence on the expression of schizophrenia related genes, which is relevant for symptoms and treatment of the disease. Specifically, improvement observed from environmental enrichment suggests that enrichment of hospital wards in inpatient psychiatric facilities might be beneficial for treatment, although it is unclear how this paradigm could be translated to humans.

Comments

Post a Comment

Popular posts from this blog

Microbiotic effects on stress and social behavior in mice- Sierra Smith

For the final week of paper discussions, we dove into the fascinating and very new topic of the gut microbiome, and the influence of microbiotic composition on mice either under chronic subordinate colony housing situations or the offspring of dames fed a high-fat diet. In the first paper I read, Reber et al, there were fascinating findings that although supplementation with heat-killed Mycobacterium vaccae did not prevent all microbiotic changes induced by stressful housing conditions, it did have a significantly protective effect on the development of spontaneous colitis and stress-induced aggravation of pre-existing inflammatory bowel disease (colitis in mice). There was also a profound effect on proactive defensive behaviors in mice housed in CSC conditions, whereas they became defeated less easily and displayed significantly more proactive behaviors when faced with an aggressor. I was particularly excited to read about the increased Iba1 immunostaining in fear-regulato...
Read more

ACC-BLA Connections and Observational Learning- Annissa DeSilva

            Observational fear learning is an innate social behavior, Allsop et al. 2018 outlines the neural circuit underlying how the brain encodes emotionally salient (fear) behavior with neutral cues associated through observational fear learning. Allsop et al, found that projections from the Anterior cingulate cortex (ACC) to the Basolateral Amygdala (BLA) are essential in encoding observational learning. Specifically observing distress causes basal changes in the ACC neurons (encoding of the observed behavior through social cues) which enables the acquisition of the predictive nature of the aversive cue by BLA neurons. When ACC - BLA projections were optogenetically inhibited while mice were observing fear conditioning a reduced freezing response was seen when conditioned fear response was tested. Interestingly when the ACC - BLA projections were inhibited during testing of observational fear conditioning the...
Read more

Two sides of the same coin?: the bidirectional effects of VTA-NAc DA neurons - Emily Jones

Papers like the ones assigned this week reminded of the reasons I opted to take this class. Research into the biological nuances of complex clinical disorders really reinforces the idea that everything psychological is simultaneously biological. And in these papers, optogenetics amazingly gives us a fast and efficient way to explore these nuances. Interestingly, both papers demonstrated a bidirectional effect of dopamine neurons in the VTA-NAc pathway on depression phenotypes using phasic photoactivation. However, it seemed that these effects were flipped. In other words, when Chaudhury et al. inhibited the neurons, a resilient phenotype was induced in previously susceptible mice (indicated by a high preference for sugar water and decreased social avoidance compared to control mice); when Tye et. al. use the same opsin to inhibit the same kind of neurons, depression phenotypes were induced. Indeed the differences may be due in large part to the different stress conditions the mice we...
Read more