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- Creators: School of Life Sciences
- Creators: Lemery-Chalfant, Kathryn
This hypothesis is supported by previous studies demonstrating that stress-induced elevation of glucocorticoids increases the transcription of C4. I propose that activated glucocorticoid receptors directly increase C4 protein expression as a transcription factor activator. Additionally, I propose that activated glucocorticoid receptors inhibit the expression of the transcription factor nuclear factor-light-chain-enhancer of activated B cells (NF-κB), thereby leading to decreased expression of the C4 inhibitor CUB and Sushi multiple domains 1 (CSMD1).
Glucocorticoid receptors and C4 are richly expressed in the hippocampus, a region critical in memory consolidation, spatial, and declarative memory. I propose that stress-induced upregulation of C4 activity in the hippocampus promotes excessive synaptic pruning, contributing to specific deficits and hippocampal shrinkage seen in schizophrenia. Stress exposure during fetal development and adolescence likely acts through the proposed mechanisms to increase hippocampal C4 activity and subsequent schizophrenia risk. These mechanisms may reveal novel interactions between environmental and genetic risk factors in the etiology of schizophrenia through complement activation.
In this project I explored the relationship between Qigong and Tai Chi Easy meditative practices and cardiometabolic risk factors, specifically looking at obesity and stress. The meditative focus of Qigong and Tai Chi Easy was expected to improve cardiac vagal tone which should lead to decreases in the inflammatory effects of stress. Additionally, due to the decreases in the harmful effects of stress, we expect to see a decrease in obesity through decreases in BMI and in waist circumference.
Exploration of a mouse model (C57BL/6J) capable of demonstrating behavioral changes after adolescent social isolation that are consistent with prior findings may prove beneficial in later research. This study examined 2 proposed long-term effects of isolated housing (one mouse/cage), when compared to group housing (two mice/cage) during adolescence. Mice were placed in their respective housing conditions after weaning (PND 21) and remained in those conditions until PND 60. The same cohorts were used in both phases of the experiment. Phase 1 sought to confirm previous findings that showed increases in ethanol intake after adolescent social isolation using a 2-bottle preference Drinking-in-the-Dark (DID) design over a 4-day period (PND 64-PND 67.). Phase 2 sought to elucidate the effects present after adolescent social isolation, as measured using response inhibition capabilities demonstrated during fixed-minimum interval (FMI) trials (PND 81-PND 111). Findings in phase 1 of the experiment were non-significant, save a strong tendency for female mice in both housing conditions to drink more as a proportion of their bodyweight (g/kg). However, a trend of lower bodyweight in single housed mice did exist, which does suggest that detrimental stress was applied via the used of adolescent isolation in that housing condition. Findings in phase 2 showed little effect of adolescent social isolation on mean inter-response time (IRT) at any criterion used (FMI-0, FMI-4, FMI-6). Evaluation of mean interquartile range (IQR) of IRTs showed a significantly greater amount of variation in IRT responses within single housed mice at the highest criterion (FMI-6), and a trend in the same direction when FMI-4 and FMI-6 were tested concurrently. Taken as a whole, the findings of this experiment suggest that the effect of adolescent social isolation on ethanol intake is far less robust than the effect of sex and may be difficult to replicate in a low-power study. Additionally, adolescent social isolation may interfere with the ability of mice to show consistent accuracy during FMI tasks or a delay in recognition of FMI criterion change.