Title

Neurological and Behavioral Mechanisms of Post-traumatic Stress Disorder in a Mouse Model

Author

Ami Bhakta

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Date of Award

Summer 2018

Abstract

Post-traumatic stress disorder (PTSD) is a mental disorder experienced by humans who were exposed to intense traumatic events. The basic pathogenesis and mechanisms of PTSD are not fully understood due to limitations of experimental models. In this present study, we used a rat-mouse predator-prey relationship to study PTSD-like symptoms and their effects on the mice. Adolescent mice (1-month-old) were exposed to aggressive rats (1-year-old) to induce chronic stress for 28 days. We conducted various behavioral tests such as the open field test, radial arm maze test, elevated plus maze test, and sucrose preference test to study their behavioral phenotypes between the control and predator-stressed mice. The predator-stressed mice showed progressively more errors in the radial arm maze test over a 5-day period (p = .035). The gene expression of corticotrophin-releasing hormone (CRH) was reduced as compared to the control mice (p < .001). Molecular studies of the hippocampus of predator-stressed mice showed increased protein expression of Interleukin (IL-β), a downregulation of mRNA transcripts of CRH, and decreased acetylcholine (a neurotransmitter) expression. There were no significant differences in levels of brain-derived neurotrophic factor (BDNF; p = .22), nerve growth factor (NGF; p = .05), and immediate early genes such as glucocorticoid receptor (NR3C1; p = .83), mineralocorticoid receptor (NR3C1; p = .22), zinc finger protein, ZIF-268 (EGR1; p = .37), activity-regulated cytoskeleton-associated protein (Arc; p = .41), and Fos proto-oncogene (c-Fos; p = .27) in the hippocampus of both groups of mice. We demonstrated that chronic stress plays a role in memory impairment, elevated inflammatory responses, as well as in the development of resilience after a recovery period.

Advisor

Kodeeswaran Parameshwaran

Subject Categories

Biology | Life Sciences | Neuroscience and Neurobiology

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