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Recent Submissions
- ItemExamining the Impact of Neonatal Pain and Infection on Dopaminergic Function During Learning in Long Evans Rats(2023) Hoffman, Dori; Robinson-Drummer, PatreseAdmission to the Neonatal Intensive Care Unit may potentially result in early life trauma. The effects of early life stressors are associated with possible disruptions to the dopaminergic system, resulting in changes to adulthood aversion. Gomes and Barr (2020) simulated the NICU experience via pain and infection exposure on rodents; experimental groups were divided into exposure to pain, to infection, combined conditions, and a non-exposed control. Aversive behavior was measured in adulthood via Conditioned Place Aversion tasks, and brain samples were collected. In the current study, we stained for tyrosine hydroxylase to measure dopaminergic change in relation to early life trauma exposure. Due to their association with dopamine expression, the ventral tegmental area and substantia nigra were targeted for immunohistochemical analysis. In the substantia nigra, there were no significant changes in tyrosine hydroxylase expression between groups; however, tissue damage limited analysis of the ventral tegmental area. These results suggest tyrosine hydroxylase expression in the substantia nigra has no impact on early life pain and infection and their association with a change in aversive behaviors during adulthood.
- ItemCamellia japonica Leaf Extract Inhibits Protein Aggregation In a Caenorhabditis elegans Model of Alzheimer’s Disease(2023) Vu, Tien; Fairman, RobertAlzheimer’s disease is a chronic and irreversible neurodegenerative disease that has affected much of the population worldwide, and thought to be the result of aggregation of amyloid-β (Aβ) peptides. As current research continues to search for effective therapeutics, there is rising interest in using plant extracts to treat Alzheimer’s symptoms and target the pathogenesis underlying the disease itself– Aβ aggregation. Camellia japonica, a tea plant native to East Asia and not well-characterized in current literature, poses potential as a therapeutic and Aβ aggregation-inhibiting agent for Alzheimer’s disease. Recent in vitro studies have found C. japonica to show neuroprotective effects against Aβ-induced toxicity and to possess polyphenolic compounds capable of mitigating protein aggregation. However, to date, there are no in vivo studies directly looking at C. japonica extract’s effects on Aβ aggregation, which this study seeks to address. The findings show that C. japonica extract is able to attenuate Aβ aggregation in a C. elegans transgenic model of Alzheimer’s disease through delaying Aβinduced paralysis, and this effect can be directly visualized via confocal microscopy. Thus, C. japonica’s inhibiting effects on Aβ aggregation suggests a novel therapeutic agent for Alzheimer’s and further potential to be developed for other neurodegenerative diseases.
- ItemThe Acer rubrum-Derived Polyphenol Ginnalin A Attenuates Amyloid Beta Toxicity in a Caenorhabditis elegans Model of Alzheimer’s Disease(2023) May, Alexander; Fairman, RobertThe pathological finding of amyloid-β (Aβ) aggregates in the brain is widely thought to be a leading cause of Alzheimer’s disease (AD). There is a current lack of disease-modifying treatments for AD, with the standard of care being solely symptomatic treatments. Some such symptomatic treatments, like EGb 761, are derived from plant extracts, demonstrating the potential for plants to be a source of novel therapeutics. Plants are known to have high levels of polyphenolic compounds, which can have aggregation-inhibiting activity. EGCG, one such compound that is found in green tea leaves, has been shown to inhibit Aβ aggregation and is currently in Phase III clinical trials, demonstrating the promising potential of polyphenols as specific compounds within plant extracts as therapeutics for AD. In this study, I demonstrated Acer rubrum leaf extract’s therapeutic potential against AD in a transgenic C. elegans model. Specifically, A. rubrum extract attenuated Aβ-induced toxicity in the form of Aβ-induced paralysis in nematodes and decreased the number of Aβ deposits in the nematodes’ body wall muscle cells. In considering the identification of specific compounds that might be responsible for the extract’s effect, I investigated Ginnalin A, a polyphenol found in A. rubrum leaves that has been shown to inhibit Aβ aggregation and to reverse fibrillogenesis in vitro. I report that Ginnalin A, like the A. rubrum extract, attenuated Aβ-induced toxicity in the form of Aβ-induced paralysis and decreased the number of Aβ deposits in the nematodes’ body wall muscle cells. This study thus provides strong evidence of anti-AD effects by A. rubrum extract and Ginnalin A, suggesting that they can potentially be used as natural preventative and therapeutic agents for AD.
- ItemThe Effects of Peripartum Estradiol Fluctuations on Mesolimbic Dopamine Dynamics(2023) Halliday, Amanda R.; Been, LauraThe peripartum period involves dramatic hormonal changes; estradiol levels increase 10-100 fold during pregnancy and drop to pre-pregnancy levels immediately following expulsion of the placenta. These drastic fluctuations are believed to play a role in peripartum mood and anxiety disorders, which affect approximately 1 in 8 birthing people. It is likely that changes to ovarian/placental hormone levels affect the mesolimbic pathway, which is an important pleasure and motivation center in the brain. However, specific mechanisms connecting estradiol fluctuations to mood and behavioral changes are not well understood. We used fast-scan cyclic voltammetry (FSCV) to characterize the effects of a hormone-simulated pseudopregnancy (HSP) on mesolimbic dopamine dynamics in female C57BL/6 mice. We found that high-dose estradiol administration during the HSP decreases dopamine release and reuptake rate in the nucleus accumbens (NAc) core. Further research will aim to supplement these findings and draw more clear connections between peripartum estradiol fluctuations, mesolimbic dopamine dynamics, and affective/behavioral changes.
- ItemThe Impact of Stress on Response Inhibition: A Stepwise Manipulation of Exposure(2023) Donahue, Rebecca; Compton, Rebecca J. (Rebecca Jean)Stress is known to have deteriorating effects on performance, but some literature suggests that to a certain degree, stress can also have enhancing effects. The Yerkes-Dodson Law Bell curve depicts that under low to moderate stress, executive functioning is enhanced, but under extreme to hard degrees, those functions are inhibited. This study sought to investigate if the effect of stress plays a role on inhibitory control. According to the Yerkes-Dodson Law Bell Curve, stress should follow a non-linear relationship and this study attempted confirm or deny this through application of a stepwise manipulation of stress exposure through mental arithmetic. Twenty-seven undergraduate students at Haverford College participated in stress manipulation and EEG testing, as well as response inhibition testing through Go/No-Go tests. Our study found that N2 amplitudes showed an expected Go/No-Go effect that varied across sites on the scalp but did not vary according to stress condition as expected. This suggests that although self-report measures initially indicated a successful stress manipulation, stress did not affect inhibitory control as hypothesized. Instead, the ERP data suggests that the level of stress induced through the stress manipulation model, did not have as significant of an actual difference between the three stress conditions as was expected.