The novel role of extracellular cardiolipin in microglial activation and neuroinflammation
department or school: Arts and Sciences, Irving K. Barber School of (Okanagan)
department or school: Biology, Department of (Okanagan)
data provider: DSpace
degree campus: UBCO
creator: Pointer, Caitlin Bennett
issued: 2017-05-01T17:33:19Z
issued: 2017
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Alzheimer’s disease (AD) is a fatal neurodegenerative disorder characterized by chronic neuroinflammation. Microglia, the immune cells of the brain, become activated in response to pathological stimuli and cellular debris. Once activated, microglia secrete pro-inflammatory mediators, as well as participate in phagocytosis in aims of eliminating the noxious stimuli. Microglial activation is normally beneficial, as it helps maintain homeostatic conditions and regulate the immune status of the brain; however, in AD, microglia become over-activated, which causes the non-specific release of cytotoxic molecules and results in extensive neuronal death. Cardiolipin, a mitochondrial phospholipid implicated in regulating metabolic processes, is significantly reduced in AD brains. Additionally, it has been shown that cardiolipin can be relocated to the outer mitochondrial membrane, as well as to the plasma membrane during various cellular processes. Although the intracellular role of cardiolipin has been well defined, the effects of extracellular cardiolipin on microglial functions implicated in AD pathogenesis have yet to be investigated. The central hypothesis of this thesis proposes that extracellular cardiolipin regulates select microglial functions. I focused on three specific research objectives: 1) to determine whether extracellular cardiolipin induces the phagocytic activity of microglia, 2) to determine whether extracellular cardiolipin affects microglial functions that impact neuronal viability and 3) to determine whether extracellular cardiolipin alters the secretory profile of microglia. By utilizing in vitro cell culture techniques and biological assays with immortalized CNS model cells, as well as primary murine microglia, I demonstrate that extracellular cardiolipin induces the phagocytic activity of microglia, decreases microglia-mediated cytotoxicity towards neurons, as well as alters the secretory profile of activated microglia by reducing the secretion of ke…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/61409
note: The Novel Role of Extracellular Cardiolipin in Microglial Activation and Neuroinflammation by Caitlin Bennett Pointer B.Sc., The University of British Columbia, 2015 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE COLLEGE OF GRADUATE STUDIES (Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Okanagan) April 2017 © Caitlin Bennett Pointer, 2017 ii Thesis Committee: Dr. Andis Klegeris (Supervisor) Dr. Bruce Mathieson Dr. Mark Rheault iii Abstract Alzheimer’s disease (AD) is a fatal neurodegenerative disorder characterized by chronic neuroinflammation. Microglia, the immune cells of the brain, become activated in response to pathological stimuli and cellular debris. Once activated, microglia secrete pro-­‐inflammatory mediators, as well as participate in phagocytosis in aims of eliminating the noxious stimuli. Microglial activation is normally beneficial, as it helps maintain homeostatic conditions and regulate the immune status of the brain; however, in AD, microglia become over-­‐activated, which causes the non-­‐specific release of cytotoxic molecules and results in extensive neuronal death. Cardiolipin, a mitochondrial phospholipid implicated in regulating metabolic processes, is significantly reduced in AD brains. Additionally, it has been shown that cardiolipin can be relocated to the outer mitochondrial membrane, as well as to the plasma membrane during various cellular processes. Although the intracellular role of cardiolipin has been well defined, the effects of extracellular cardiolipin on microglial functions implicated in AD pathogenesis have yet to be investigated. The central hypothesis of this thesis proposes that extracellular cardiolipin regulates select microglial functions. I focused on three specific research objectives: 1) to determine whether extracellular cardiolipin induces the phagocytic activity of microglia, 2) to determine whether extracellular cardiolipin affects microglial functions that …
has type: Thesis/Dissertation
date issued: 2017-05
is shown at: 10.14288/1.0347222
language: eng
degree discipline: 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/2429/61409