Skip to main content

Final Paper Proposal

By
One topic that has particularly fascinated me is the effects of endocrine disrupting compounds (EDC) on the brain. Chemicals that are prevalent in people's everyday lives, like Bisphenol-A (BPA) and phthalates, found in canned goods and plasticizers, respectively, can have profound impacts on brain function. Though BPA and phthalates are some of the most common EDC's, many others exist in products such as pesticides, herbicides and cosmetics. Interestingly, these effects can persist across multiple generations, altering the neurodevelopment of offspring that were never exposed to these EDC's first-hand. However, robust effects are also seen in animal models where the first generation were directly exposed to a specific EDC.

 The reason I find EDC's so interesting is because the dysfunction they cause is a direct result of environmental exposure. Not only do these exogenous chemicals have detrimental consequences for the organism that is exposed to them, but for their offspring as well. These consequences include impaired hippocampal neurogenesis and altered gene expression in structures like the amygdala, hypothalamus (Hatcher, 2019) and PFC (Sadowski, 2014). To add another layer of complexity, many studies consider both males and females, noting sexual dimorphisms in how endocrine disruptors affect the brain and, in turn, behavior. Therefore, I think it is relevant to consider how epigenetic and neurodevelopmental changes due to EDC exposure can predispose individuals to psychiatric disorders such as PTSD, anxiety and schizophrenia in both males and females.
Sources:

Hatcher, K. M., Willing, J., Chiang, C., Rattan, S., Flaws, J. A., & Mahoney, M. M. (2019). Exposure to di-(2-ethylhexyl) phthalate transgenerationally alters anxiety-like behavior and amygdala gene expression in adult male and female mice. Physiology and Behavior, 207, 7-14. https://doi.org/10.1016/j.physbeh.2019.04.018
Jang, Y.J., Park, H.R., Kim, T.H., Yang, W., Lee, J., Choi, S.Y., Oh, S.B., Lee, E., Park, J., Kim, H., Kim, H.S., & Lee, J. (2012). High dose bisphenol A impairs hippocampal neurogenesis in female mice across generations. Toxicology, 296 1-3, 73-82 .

Kitraki E, Nalvarte I, Alavian-Ghavanini A, Rüegg J. Developmental exposure to bisphenol A alters expression and DNA methylation of Fkbp5, an important regulator of the stress response. Molecular and Cellular Endocrinology. 2015 Dec;417:191-199. DOI: 10.1016/j.mce.2015.09.028.

Sadowski, R.N., Wise, L.M., Park, P.Y., Schantz, S.L., & Juraska, J.M. (2014). Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females. Neuroscience, 279, 122-131.

Skinner MK, Anway MD, Savenkova MI, Gore AC, Crews D (2008) Transgenerational Epigenetic Programming of the Brain Transcriptome and Anxiety Behavior. PLoS ONE 3(11): e3745. doi:10.1371/journal.pone.0003745





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