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Title:Assessment of the impact of early life trauma, changes in estrogen signaling, and neurotoxic molecules in a mouse model of multiple sclerosis
Author(s):Khaw, Yee Ming
Director of Research:Inoue, Makoto
Doctoral Committee Chair(s):Inoue, Makoto
Doctoral Committee Member(s):Ko, Chemyong; Steelman, Andrew J; McKim, Daniel B
Department / Program:Neuroscience Program
Discipline:Neuroscience
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Multiple sclerosis, neuron, EAE, inflammation
Abstract:Multiple sclerosis (MS) is the most common neurological disease that affect young adults that causes the accumulation of disability over time due to irreversible neurodegeneration. Disease presentations vary significantly from person to person in terms of who gets the disease, who develops the more severe types of MS, the type of central nervous system injury that the disease inflicts, molecular signatures on disease driving immune cells, and one’s sensitivity to prescribed treatment. While it is a deeply heterogenous disease, MS is widely accepted to be driven by an autoimmune response characterized by the infiltration of peripheral immune cells and activation of CNS-resident glial cells which results in demyelination, loss of oligodendrocytes, neuron atrophy. The etiology of MS is undetermined. Several genetic and non-genetic (a.k.a. environmental) factors have been identified to have significant impact on disease activity and its underlying mechanism. Importantly, evidence suggest that non-genetic environmental factors play a significant role in disease modification by acting on cellular drivers of the disease. Herein, using a MS model of experimental autoimmune encephalomyelitis (EAE) in four independent projects, I report that non-genetic environmental factors of early life stress, changes in estrogen level, immune cell expression of neurotoxic molecule contribute to disease heterogeneity. The studies also highlight the identity of membrane lymphotoxin-lymphotoxin receptor beta receptor signaling and CXCR2 signaling as potential biomarkers for neurodegenerative and interferon-beta resistant MS and EAE.
Issue Date:2021-11-29
Type:Thesis
URI:http://hdl.handle.net/2142/114076
Rights Information:Copyright 2021 Yee Ming Khaw
Date Available in IDEALS:2022-04-29
Date Deposited:2021-12


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