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UBC Theses and Dissertations

The effects of dietary fatty acids on microglial immune responses Lowry, Jessica Rae

Abstract

The increasing number of Canadians with dementia is projected to reach one million by 2033. The most common cause of dementia is Alzheimer’s disease (AD). Modifiable risk factors for AD, including dietary factors, should be investigated to inform recommendations for disease prevention. Dietary fatty acids, including polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs), are modifiable dietary components. PUFAs affect immune functions in the periphery and the central nervous system (CNS). Microglia are CNS immune cells that release inflammatory mediators including chemokines, cytokines, reactive nitrogen species (RNS) and reactive oxygen species (ROS). In AD, microglia are chronically activated by abnormal proteins, which results in excessive production of inflammatory mediators, promoting neuron death. The fatty acids studied in this thesis included the n-3 and n-6 PUFAs α-linolenic acid (ALA) and linoleic acid (LA), the MUFA oleic acid (OA), and the SFA stearic acid (SA). While this thesis presents experiments containing two glucose conditions, effects of fatty acids on the microglial release of RNS, ROS, monocyte chemoattractant protein (MCP)-1 and neurotoxins were examined using high glucose conditions (17.0-17.3 mM). Gas chromatography assessed fatty acid content of cells exposed to fatty acids in the presence of 5.6 mM and 17.0 mM glucose. The Griess assay assessed RNS, followed by immunoblotting for inducible nitric oxide synthase (iNOS). Chemiluminescence was used to measure ROS, and enzyme-linked immunosorbent assays were used to detect MCP-1. Neuronal SH-SY5Y cells were incubated with supernatants from microglia exposed to fatty acid to assess impact of released neurotoxins. In activated BV-2 microglia cultured in high glucose media (17.0 mM), fatty acids ALA and LA reduced microglial RNS release, and LA reduced the expression of iNOS. In microglia cultured in high glucose media (17.0-17.3 mM), no effects of fatty acids on phagocytosis, ROS release and MCP-1 release were identified. Except for SA, each fatty acid studied did not affect neurotoxic microglial secretions. My thesis demonstrates that dietary fatty acids inhibit select immune responses of microglia cultured in high glucose (17.0 mM). This data extends our knowledge basis needed for evidence-based dietary recommendations to prevent CNS inflammation.

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