BACKGROUND: In recent years, studies have increasingly pointed to a number of different mechanisms that potentially form the foundation for the neurodegenerative pathology seen in Post-Traumatic Stress Disorder (PTSD). One such mechanism is neural damage due to oxidative stress. This study attempted to identify significantly altered expression levels of particular genes of interest between PTSD and control groups, as well as between PTSD samples and samples exhibiting commonly seen PTSD comorbidities, major depressive disorder (MDD), and depressive disorder not otherwise specified (DepNOS). The genes of interest being pursued in the study encompass the production of reactive oxygen species, such as inflammatory response mechanisms, the processes that control the removal of reactive oxygen species (ROS), and genes that are activated in response to oxidative stress. Other genes of interest involve factors important in the structural integrity of the prefrontal cortex, such as junction proteins, the blood-brain barrier, such as aquaporins, and neuronal integrity. These genes were included due to the evidence of structural degeneration in PTSD patients. A total of 54 genes were tested in all four groups.
OBJECTIVES: To identify and determine genetic differences amongst individuals with PTSD in comparison to non-PTSD sufferers, and sufferers of common PTSD comorbidities.
METHODS: The expression levels of the genes of interest were measured using quantitative polymerase chain reaction (qPCR) techniques. RNA is extracted and collected from tissues samples of deceased military PTSD patients from the prefrontal cortex. The prefrontal cortex derived RNA is used as the experimental samples, due to the prevalence of the pathology of PTSD in this region. Complimentary DNA (cDNA) is reverse transcribed from the collected RNA, and then products of genes of interest are amplified during the qPCR reaction using specifically designed primers. The expression level of the genes of interest were then compared to the ubiquitously expressed gene 18s for normalization calculations. Genetic expression levels in the PTSD, MDD, and DepNOS cohorts were then normalized to the expression of non-PTSD controls.
RESULTS: Of the 54 genes of interest analyzed, two genes, NQO1 and IL-6, exhibited significantly decreased and increased levels of expression in comparison to the control group, respectively (p < 0.05). Alongside this, NQO1 showed significantly decreased expression in comparison to the DepNOS cohort, while IL-6 exhibited significantly increased expression in comparison to the MDD cohort (p < 0.05).
CONCLUSION: Two genes involved with the production and elimination of reactive oxygen species were identified with having significantly altered levels of expression. NQO1, which facilitates the removal of ROS was shown to have significantly lower expression when compared to the control group, indicating an inhibited ability to remove ROS readily. Furthermore, IL-6, a proinflammatory cytokine and a promotor of ROS production, exhibited significantly increased expression, indicating a potential increase in ROS formation. Together these results indicate a potential mechanism for the production and accumulation of ROS in patients with PTSD, leading to the observed neurodegeneration. / 2018-07-11T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/23732 |
| Date | 12 July 2017 |
| Creators | Restaino, Anthony Cole |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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