Signaling between gut microbiota and brain immune cells
department or school: Arts and Social Sciences, Irving K. Barber Faculty of (Okanagan)
department or school: Biochemistry and Molecular Biology, Department of
data provider: DSpace
degree campus: UBCO
creator: Gates, Ellen Joan
issued: 2020-10-06T22:22:49Z
issued: 2020
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Neuroinflammation is a key pathophysiological feature of neurodegenerative disorders including Alzheimer’s disease. Neuroinflammation occurs when microglia, brain immune cells, become chronically activated and excessively secrete inflammatory molecules, such as reactive oxygen and nitrogen species, tumour necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1. This overactivation of the brain immune system can lead to damage and death of healthy neurons. Identifying the mediators that regulate microglial activation in the central nervous system (CNS) is imperative for the development of new therapies that treat or prevent neuroinflammation. Recent evidence shows that bacteria that inhabit the gut are key players in the communication between the gut and brain and may mediate neuroinflammation. Therefore, the bacterial metabolites D-serine, trimethylamine N-oxide (TMAO), formate, and valerate, as well as the related endogenous signaling molecule Interleukin (IL)-2, were tested for their ability to modulate select microglial functions. To test this hypothesis, the cell-mediated neurotoxicity assay was used to determine the toxic effects of human microglia-like cells towards human SH-SY5Y neuronal cells. Enzyme-linked immunosorbent assays were utilized to determine the secretion levels of TNF-α and MCP-1 by microglia-like cells. The Griess assay and chemiluminescence were used to quantify the secretion of reactive nitrogen and oxygen species, respectively, by microglia-like cells and the phagocytosis assay was utilized to quantify the phagocytic activity of microglia-like cells. It was determined that formate and valerate inhibited secretion of TNF-α and MCP-1 by microglia-like cells and decreased their toxicity towards SH-SY5Y neurons. D-Serine, TMAO, and IL-2 had no effects on these parameters. D-Serine, formate, and IL-2 inhibited the secretion of reactive oxygen species by microglia-like cells, while valerate and TMAO showed no effect. D-Serine, forma…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/76265
note: i Signaling Between Gut Microbiota and Brain Immune Cells by Ellen Joan Gates B.Sc., The University of Saskatchewan, 2017 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE COLLEGE OF GRADUATE STUDIES (Biochemistry and Molecular Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Okanagan) October 2020 © Ellen Joan Gates, 2020 ii The following individuals certify that they have read, and recommend to the College of Graduate Studies for acceptance, a thesis/dissertation entitled: SIGNALING BETWEEN GUT MICROBIOTA AND BRAIN IMMUNE CELLS submitted by Ellen Gates in partial fulfillment of the requirements of the degree of Master of Science . Dr. Andis Klegeris; Irving K. Barber Faculty of Science Supervisor Dr. Bruce Mathieson; Irving K. Barber Faculty of Science Supervisory Committee Member Dr. Mark Rheault; Irving K. Barber Faculty of Science Supervisory Committee Member Dr. Robert Godin; Irving K. Barber Faculty of Science University Examiner iii Abstract Neuroinflammation is a key pathophysiological feature of neurodegenerative disorders including Alzheimer’s disease. Neuroinflammation occurs when microglia, brain immune cells, become chronically activated and excessively secrete inflammatory molecules, such as reactive oxygen and nitrogen species, tumour necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1. This overactivation of the brain immune system can lead to damage and death of healthy neurons. Identifying the mediators that regulate microglial activation in the central nervous system (CNS) is imperative for the development of new therapies that treat or prevent neuroinflammation. Recent evidence shows that bacteria that inhabit the gut are key players in the communication between the gut and brain and may mediate neuroinflammation. Therefore, the bacterial metabolites D-serine, trimethylamine N-oxide (TMAO), formate, and valerate, as well as the related endogenous signaling molecule Interleukin …
has type: Thesis/Dissertation
date issued: 2020-11
is shown at: 10.14288/1.0394714
language: eng
degree discipline: Biochemistry and Molecular Biology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/76265