Matching Items (142)
Description
Since its inception in the early 1990s, the concept of gene vaccines, particularly DNA vaccines, has enticed researchers across the board due to its simple design, flexible modification, and overall inexpensive cost of manufacturing. However, the past three decades have proven to be less fruitful than anticipated as scientists have yet to tackle the issue of inducing a strong enough response in humans and non-human primates to protect against foreign pathogens, an issue that has since been coined as the “simian barrier.” This appears to be a human/primate barrier as protective vaccines have been produced for other mammals. Despite millions of dollars in research along with some of the world’s brightest minds chipping in to resolve this, there has yet to be any truly viable solution to overcoming this barrier. With current research illustrating effective applications of RNA vaccines in humans, these studies may be uncovering the solution to the largely unsolved simian barrier dilemma. If vaccines using RNA, the transcribed version of DNA, are effective in humans, the problem may be inefficient transcription of the DNA. This may be attributable to a DNA promoter that has insufficient activity in primates. Additionally, with DNA vaccines being even cheaper and easier to manufacture than RNA vaccines, along with having no required cold chain for distribution, this concept remains more promising than RNA vaccines that are further along in clinical trials.
ContributorsWillis, Joshua Aaron (Author) / Johnston, Stephen (Thesis director) / Sykes, Kathryn (Committee member) / Shen, Luhui (Committee member) / Dean, W.P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
Description
Major Depressive Disorder (MDD) is a common mental disorder that can affect individuals at nearly every stage of life. Women are especially vulnerable to MDD in part, from ovarian hormone level fluctuations. In this thesis, I focused on MDD using a rat model in middle-age to explore potential sex differences in response to a corticosterone (CORT) – induced depressive-like state. Estradiol (E2), a naturally occurring steroid sex hormone in humans and rats, is implicated in mood changes, which is especially prominent during the menopause transition. CORT, a stress hormone, was used to create a depressive-like state in middle-aged female (F) and male (M) rats with their gonads surgically removed. This produced the following independent treatment groups: Sex (F, M), CORT (vehicle = V ml/kg, C 40mg/kg), E2 (V 0.1 ml, E 0.3µg/0.1ml). CORT and E2 injections were injected daily, s.c) for 7 days before behavioral testing began and continued throughout the study when behavior was assessed. For my honor’s thesis, I focused on the social interaction test and elevated plus maze to investigate whether CORT enhanced social avoidance and anxiety, and whether E2 mitigated the CORT effects. In the social interaction test, three new behaviors were assessed (interacting, grooming, and immobility) to better understand exploratory and anxiety profiles of the rats, and these behaviors were quantified over two 5-minute periods in the 10-minute trial. These new quantifications showed that for the female rats, C+E and V+V enhanced the interaction with the novel rat significantly more than an inanimate object, which was not observed in the females given CORT only or E2 only. The males in all conditions showed a significant preference for side with the novel rat compared to the object, however no treatment differences were observed. In both sexes, the overall time spent interacting decreased in the second five minutes of quantification compared to the first five minutes. No effects were observed with grooming or immobility, in part from the high variability across rats. For EPM, female rats treated with CORT and E2 exhibited a lower anxiety index than compared to female rats given CORT only, indicating that E2 mitigated the depressive-like effects of CORT. Males showed no CORT or E2 effects. The result in part supported my hypothesis, as the CORT-treated females exhibited reduced socialization and E2 improved socialization in CORT-treated females, as this was seen in the F-C-E group. Interestingly, CORT failed to produce a depressive-like effect in males in both behavioral tests, which was an unexpected outcome. These results suggest that administration of E2 with CORT mitigated the depressive-like state created by CORT in female rats, however failed to produce these outcomes in males. The outcome of this work will give us insight into the potential mechanisms that may contribute to sex differences with MDD.
ContributorsSladkova, Sara (Author) / Conrad, Cheryl (Thesis director) / Amdam, Gro (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2024-05