The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus
Abstract Background Neuroinflammation is thought to contribute to psychiatric and neurological disorders such as major depression and Alzheimer’s disease (AD). N-6 polyunsaturated fatty acids (PUFA) and molecules derived from them, including linoleic acid- and arachidonic acid-derived lipid mediator...
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doaj-d69e459ee09e463f92bb80b64b852c0f2020-11-25T02:39:26ZengBMCJournal of Neuroinflammation1742-20942019-11-0116111610.1186/s12974-019-1615-0The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampusShoug M. Alashmali0Lin Lin1Marc-Olivier Trépanier2Giulia Cisbani3Richard P. Bazinet4Department of Clinical Nutrition, Faculty of Applied Medical Sciences, King Abdul Aziz UniversityDepartment of Nutritional Sciences, Faculty of Medicine, University of TorontoDepartment of Nutritional Sciences, Faculty of Medicine, University of TorontoDepartment of Nutritional Sciences, Faculty of Medicine, University of TorontoDepartment of Nutritional Sciences, Faculty of Medicine, University of TorontoAbstract Background Neuroinflammation is thought to contribute to psychiatric and neurological disorders such as major depression and Alzheimer’s disease (AD). N-6 polyunsaturated fatty acids (PUFA) and molecules derived from them, including linoleic acid- and arachidonic acid-derived lipid mediators, are known to have pro-inflammatory properties in the periphery; however, this has yet to be tested in the brain. Lowering the consumption of n-6 PUFA is associated with a decreased risk of depression and AD in human observational studies. The purpose of this study was to investigate the inflammation-modulating effects of lowering dietary n-6 PUFA in the mouse hippocampus. Methods C57BL/6 male mice were fed either an n-6 PUFA deprived (2% of total fatty acids) or an n-6 PUFA adequate (23% of total fatty acids) diet from weaning to 12 weeks of age. Animals then underwent intracerebroventricular surgery, in which lipopolysaccharide (LPS) was injected into the left lateral ventricle of the brain. Hippocampi were collected at baseline and following LPS administration (1, 3, 7, and 14 days). A microarray (n = 3 per group) was used to identify candidate genes and results were validated by real-time PCR in a separate cohort of animals (n = 5–8 per group). Results Mice administered with LPS had significantly increased Gene Ontology categories associated with inflammation and immune responses. These effects were independent of changes in gene expression in any diet group. Results were validated for the effect of LPS treatment on astrocyte, cytokine, and chemokine markers, as well as some results of the diets on Ifrd2 and Mfsd2a expression. Conclusions LPS administration increases pro-inflammatory and lipid-metabolizing gene expression in the mouse hippocampus. An n-6 PUFA deprived diet modulated inflammatory gene expression by both increasing and decreasing inflammatory gene expression, without impairing the resolution of neuroinflammation following LPS administration.http://link.springer.com/article/10.1186/s12974-019-1615-0NeuroinflammationLipopolysaccharideN-6 polyunsaturated fatty acidsmRNAHippocampusArachidonic acid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shoug M. Alashmali Lin Lin Marc-Olivier Trépanier Giulia Cisbani Richard P. Bazinet |
spellingShingle |
Shoug M. Alashmali Lin Lin Marc-Olivier Trépanier Giulia Cisbani Richard P. Bazinet The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus Journal of Neuroinflammation Neuroinflammation Lipopolysaccharide N-6 polyunsaturated fatty acids mRNA Hippocampus Arachidonic acid |
author_facet |
Shoug M. Alashmali Lin Lin Marc-Olivier Trépanier Giulia Cisbani Richard P. Bazinet |
author_sort |
Shoug M. Alashmali |
title |
The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus |
title_short |
The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus |
title_full |
The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus |
title_fullStr |
The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus |
title_full_unstemmed |
The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus |
title_sort |
effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2019-11-01 |
description |
Abstract Background Neuroinflammation is thought to contribute to psychiatric and neurological disorders such as major depression and Alzheimer’s disease (AD). N-6 polyunsaturated fatty acids (PUFA) and molecules derived from them, including linoleic acid- and arachidonic acid-derived lipid mediators, are known to have pro-inflammatory properties in the periphery; however, this has yet to be tested in the brain. Lowering the consumption of n-6 PUFA is associated with a decreased risk of depression and AD in human observational studies. The purpose of this study was to investigate the inflammation-modulating effects of lowering dietary n-6 PUFA in the mouse hippocampus. Methods C57BL/6 male mice were fed either an n-6 PUFA deprived (2% of total fatty acids) or an n-6 PUFA adequate (23% of total fatty acids) diet from weaning to 12 weeks of age. Animals then underwent intracerebroventricular surgery, in which lipopolysaccharide (LPS) was injected into the left lateral ventricle of the brain. Hippocampi were collected at baseline and following LPS administration (1, 3, 7, and 14 days). A microarray (n = 3 per group) was used to identify candidate genes and results were validated by real-time PCR in a separate cohort of animals (n = 5–8 per group). Results Mice administered with LPS had significantly increased Gene Ontology categories associated with inflammation and immune responses. These effects were independent of changes in gene expression in any diet group. Results were validated for the effect of LPS treatment on astrocyte, cytokine, and chemokine markers, as well as some results of the diets on Ifrd2 and Mfsd2a expression. Conclusions LPS administration increases pro-inflammatory and lipid-metabolizing gene expression in the mouse hippocampus. An n-6 PUFA deprived diet modulated inflammatory gene expression by both increasing and decreasing inflammatory gene expression, without impairing the resolution of neuroinflammation following LPS administration. |
topic |
Neuroinflammation Lipopolysaccharide N-6 polyunsaturated fatty acids mRNA Hippocampus Arachidonic acid |
url |
http://link.springer.com/article/10.1186/s12974-019-1615-0 |
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