Semester

Spring

Date of Graduation

2020

Document Type

Thesis

Degree Type

MS

College

School of Medicine

Department

Exercise Physiology

Committee Chair

Paul Chantler

Committee Member

I. Mark Olfert

Committee Member

Randall Bryner

Abstract

Obesity and psychological stress are major risk factors for cardiovascular disease and have a positive correlation with vascular dysfunction. This functional deficit has been linked to a pro-inflammatory milieu, exacerbated by an upregulation of pro-inflammatory cytokines. Febuxostat, a xanthine oxidase inhibitor, has been shown to rescue vascular impairment in these models. The purpose of this study was to examine the individual and combined effects of obesity and chronic stress on neuroimmune cell populations, and assess if febuxostat is able mediate immune alterations.

Male mice (n=48) were assigned into either normal chow (lean) and high-fat diet (obese) groups. The lean animals were then separated into one of four subgroups (n=6/group): 1) lean control, 2) lean control + febuxostat, 3) lean unpredictable chronic mild stress (UCMS), 4) lean UCMS + febuxostat. The obese counterparts were also separated into four subgroups: 1) obese control, 2) obese control + febuxostat, 3) obese UCMS, 4) obese UCMS + febuxostat. Febuxostat (50mg/L) was delivered in drinking water. Stressed mice were subjected to the UCMS paradigm which included cage tilt, no bedding, damp bedding, bath, social stress, and altered light-dark cycles for 7 hours a day, 5 days a week for 8 weeks. Coat scores were assessed to confirm the implementation of the UCMS protocol. Immediately following terminal procedures, brains were collected and processed for flow cytometry, to identify immune cell populations.

Obese animals showed a significant increase in body mass (p

These data suggest that the acquisition of obesity and/or subjection to chronic stress leads to negative alterations in immune cell subsets.

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