University of Illinois Urbana-Champaign

Expression and regulation of the rate-limiting enzymes of the kynurenine pathway in the mouse brain

Brooks, Alexandra Kelly

Content Files
BROOKS-DISSERTATION-2017.pdf

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https://hdl.handle.net/2142/97581

Description

Title
Expression and regulation of the rate-limiting enzymes of the kynurenine pathway in the mouse brain
Author(s)
Brooks, Alexandra Kelly
Issue Date
2017-04-20
Director of Research (if dissertation) or Advisor (if thesis)
McCusker, Robert H.
Doctoral Committee Chair(s)
McCusker, Robert H.
Committee Member(s)
  • Johnson, Rodney W.
  • Steelman, Andrew J.
  • Uddin, Eva M
Department of Study
Neuroscience Program
Discipline
Neuroscience
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2017-08-10T19:52:02Z
Keyword(s)
  • Indoleamine
  • Kynurenine
  • Desipramine
  • Depression
  • Inflammation
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.
Graduation Semester
2017-05
Type of Resource
text
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http://hdl.handle.net/2142/97581
Copyright and License Information
Copyright 2017 Alexandra Brooks

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Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations - Neuroscience