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Increased brain docosahexaenoic acid has no effect on the resolution of neuroinflammation following intracerebroventricular lipopolysaccharide injection.
Neurochem Int 2018; 118:115-126NI

Abstract

Resolution of inflammation in the periphery was once thought to be a passive process, but new research now suggests it is an active process mediated by specialized pro-resolving lipid mediators (SPM) derived from omega-3 polyunsaturated fatty acids (n-3 PUFA). However, this has yet to be illustrated in neuroinflammation. The purpose of this study was to measure resolution of neuroinflammation and to test whether increasing brain docosahexaenoic acid (DHA) affects the resolution of neuroinflammation. C57Bl/6 mice, fat-1 mice and their wildtype littermates, fed either fish oil or safflower oil, received lipopolysaccharide (LPS) in the left lateral ventricle. Animals were then euthanized at various time points for immunohistochemistry, gene expression, and lipidomic analyses. Peak microglial activation was observed at 5 days post-surgery and the resolution index was 10 days. Of the approximately 350 genes significantly changed over the 28 days post LPS injection, 130 were uniquely changed at 3 days post injection. No changes were observed in the bioactive mediator pools. However, a few lysophospholipid species were decreased at 24hr post surgery. When brain DHA is increased, microglial cell density did not resolve faster and did not alter gene expression. In conclusion, resolution of neuroinflammation appears to be independent of SPM. Increasing brain DHA had no effect in this model.

Authors+Show Affiliations

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 3E2, Canada.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 3E2, Canada.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 3E2, Canada.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 3E2, Canada; Lipid Biology, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 3E2, Canada. Electronic address: richard.bazinet@utoronto.ca.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29792954

Citation

Trépanier, Marc-Olivier, et al. "Increased Brain Docosahexaenoic Acid Has No Effect On the Resolution of Neuroinflammation Following Intracerebroventricular Lipopolysaccharide Injection." Neurochemistry International, vol. 118, 2018, pp. 115-126.
Trépanier MO, Hopperton KE, Giuliano V, et al. Increased brain docosahexaenoic acid has no effect on the resolution of neuroinflammation following intracerebroventricular lipopolysaccharide injection. Neurochem Int. 2018;118:115-126.
Trépanier, M. O., Hopperton, K. E., Giuliano, V., Masoodi, M., & Bazinet, R. P. (2018). Increased brain docosahexaenoic acid has no effect on the resolution of neuroinflammation following intracerebroventricular lipopolysaccharide injection. Neurochemistry International, 118, pp. 115-126. doi:10.1016/j.neuint.2018.05.010.
Trépanier MO, et al. Increased Brain Docosahexaenoic Acid Has No Effect On the Resolution of Neuroinflammation Following Intracerebroventricular Lipopolysaccharide Injection. Neurochem Int. 2018;118:115-126. PubMed PMID: 29792954.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased brain docosahexaenoic acid has no effect on the resolution of neuroinflammation following intracerebroventricular lipopolysaccharide injection. AU - Trépanier,Marc-Olivier, AU - Hopperton,Kathryn E, AU - Giuliano,Vanessa, AU - Masoodi,Mojgan, AU - Bazinet,Richard P, Y1 - 2018/05/22/ PY - 2018/02/20/received PY - 2018/05/17/revised PY - 2018/05/21/accepted PY - 2018/5/25/pubmed PY - 2018/5/25/medline PY - 2018/5/25/entrez KW - Lipopolysaccharide KW - Microglia KW - Neuroinflammation KW - Omega-3 polyunsaturated fatty acids KW - Resolution of neuroinflammation SP - 115 EP - 126 JF - Neurochemistry international JO - Neurochem. Int. VL - 118 N2 - Resolution of inflammation in the periphery was once thought to be a passive process, but new research now suggests it is an active process mediated by specialized pro-resolving lipid mediators (SPM) derived from omega-3 polyunsaturated fatty acids (n-3 PUFA). However, this has yet to be illustrated in neuroinflammation. The purpose of this study was to measure resolution of neuroinflammation and to test whether increasing brain docosahexaenoic acid (DHA) affects the resolution of neuroinflammation. C57Bl/6 mice, fat-1 mice and their wildtype littermates, fed either fish oil or safflower oil, received lipopolysaccharide (LPS) in the left lateral ventricle. Animals were then euthanized at various time points for immunohistochemistry, gene expression, and lipidomic analyses. Peak microglial activation was observed at 5 days post-surgery and the resolution index was 10 days. Of the approximately 350 genes significantly changed over the 28 days post LPS injection, 130 were uniquely changed at 3 days post injection. No changes were observed in the bioactive mediator pools. However, a few lysophospholipid species were decreased at 24hr post surgery. When brain DHA is increased, microglial cell density did not resolve faster and did not alter gene expression. In conclusion, resolution of neuroinflammation appears to be independent of SPM. Increasing brain DHA had no effect in this model. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/29792954/Increased_brain_docosahexaenoic_acid_has_no_effect_on_the_resolution_of_neuroinflammation_following_intracerebroventricular_lipopolysaccharide_injection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(18)30073-1 DB - PRIME DP - Unbound Medicine ER -