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Title:Expression and regulation of the rate-limiting enzymes of the kynurenine pathway in the mouse brain
Author(s):Brooks, Alexandra Kelly
Director of Research:McCusker, Robert H.
Doctoral Committee Chair(s):McCusker, Robert H.
Doctoral Committee Member(s):Johnson, Rodney W.; Steelman, Andrew J.; Uddin, Eva M
Department / Program:Neuroscience Program
Degree Granting Institution:University of Illinois at Urbana-Champaign
Abstract:During the mid-1900’s, early anti-depressants were developed to increase levels of catecholamines within the brain, leading to the theory that depression symptomology was a result of an imbalance of neurotransmitters within the brain. To date, the catecholamine theory of depression is still held to be the prevailing theory as selective serotonin reuptake inhibitors being the most commonly prescribed anti-depressants. However, the incidence of depression is still rising with a vast amount of patients failing to respond to current treatments, and with this knowledge, additional theories of the neurobiology of depression have arisen over the past 30 years. A leading theory is Kynurenine Pathway activation in relation to inflammation- or stress-induced depression-like behaviors. There has been a tremendous amount of data connecting activated immune system (or hypothalamic-pituitary-adrenal axis), increased kynurenine production and depression symptomology. Thus, understanding the factors that activate this pathway, as well as determining a relationship between anti-depressants and regulation of the Kynurenine Pathway, is an important next step in understanding the complex etiology of depression. My work has focused on 1) describing interactions between inflammation and stress to accentuate the expression of rate-limiting enzymes (indoleamine/tryptophan-2,3-dioxygenase: DOs) that metabolize the essential amino acid tryptophan to kynurenine, 2) detailing a novel interaction between galectins and interferon-gamma to accentuate DO expression within the brain, and finally 3) discuss the ability of current anti-depressant desipramine to block these interactions and attenuate DO expression within the brain and periphery as a possible new mechanism by which anti-depressants may be working to reduce depression symptomology.
Issue Date:2017-04-20
Rights Information:Copyright 2017 Alexandra Brooks
Date Available in IDEALS:2017-08-10
Date Deposited:2017-05

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