The Role of Dietary N-6 Polyunsaturated Fatty Acids on Lipid Mediators and Inflammation in the Mouse Brain
Year: 2019
Type: dissertation
Abstract: N-6 polyunsaturated fatty acids (PUFA) such as arachidonic acid (ARA, 20:4) and n-3 PUFA as docosahexaenoic acid (DHA, 22:6) are precursors to bioactive lipid mediators, which have important roles in many brain functions including inflammation. Previous studies have shown that dietary n-6 PUFA deprivation in pups can change brain ARA and DHA levels. However, the effects of n-6 PUFA deprivation on brain lipid metabolism during maternal stage has yet to be studied. Moreover, n-6 PUFA have been linked to the pathogenesis of many neurological disorders through many mechanisms, including conversion to ARA-derived lipid mediators (pro-inflammatory mediators) in the brain. Though diets low in n-6 PUFA are known to reduce levels of ARA and ARA-derived lipid mediators, no one has yet investigated the effects of lowering dietary n-6 PUFA on modulating brain inflammation and resolution in neuroinflammation. The first objective of this thesis was to examine how lowering dietary n-6 PUFA, from gestation, would change levels of hippocampal n-6 and n-3 PUFA and their lipid mediators in comparison to the offspring period. We found that maternal exposure to an n-6 PUFA deprived diet does not exacerbate the reduction in ARA and ARA-derived lipid mediators within hippocampal phospholipids (PL) relative to offspring exposure, which suggests that offspring exposure is a main regulating factor of these PUFA and their derivatives. Therefore, we used the offspring stage as the feeding period for the subsequent neuroinflammation study. Neuroinflammation was induced using intracerebroventricular injection of lipopolysaccharide (LPS) and the hippocampus was examined at several time points. Following LPS, different pro-inflammatory gene expression was associated with enrichment in gene expression categories associated with inflammation. However, these pro-inflammatory markers were not reduced by lowering dietary n-6 PUFA and importantly did not impair the resolution of neuroinflammation. In conclusion, we found that exposure of the offspring to an n-6 PUFA deprived diet was sufficient to lower the concentrations of ARA and other n-6 PUFA in hippocampal total PL. In a neuroinflammation model, the expression in gene ontology categories associated with inflammation was significantly increased and then resolved in response to LPS administration, however, irrespective of an n-6 PUFA diet.
Source: TSpace (University of Toronto)
Author: Shoug Alashmali
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3156631827