ArticleJournal of neurochemistry2013
Unesterified docosahexaenoic acid is protective in neuroinflammation.
Article in Journal of neurochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
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- Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.Prostaglandins, leukotrienes, and essential fatty acids · 2014Trial
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- Omega-3 Fatty Acids and Alzheimer's Disease: Toward a New Understanding of Neuroprotective Mechanisms and Intervention Strategies.Marine drugs · 2026Review
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- Strategic delivery of omega-3 fatty acids for modulating inflammatory neurodegenerative diseases.Frontiers in aging neuroscience · 2025Article
- Effects of age on lacrimal gland bioactive lipids.The ocular surface · 2024Article
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- Nutrient insufficiencies and deficiencies involved in the pathogenesis of bruxism (Review).Experimental and therapeutic medicine · 2023Review
- n-3 Polyunsaturated Fatty Acids Modulate LPS-Induced ARDS and the Lung-Brain Axis of Communication in Wild-Type versus Fat-1 Mice Genetically Modified for Leukotriene B4 Receptor 1 or Chemerin Receptor 23 Knockout.International journal of molecular sciences · 2023Article
- Neuroinflammation, Energy and Sphingolipid Metabolism Biomarkers Are Revealed by Metabolic Modeling of Autistic Brains.Biomedicines · 2023Article
- Probing changes in brain esterified oxylipin concentrations during the early stages of pathogenesis in Alzheimer's Disease transgenic rats.Neuroscience letters · 2022Article
- Ketogenic Diet: An Effective Treatment Approach for Neurodegenerative Diseases.Current neuropharmacology · 2022Review
- Imaging the Influence of Red Blood Cell Docosahexaenoic Acid Status on the Expression of the 18 kDa Translocator Protein in the Brain: A [Biological psychiatry. Cognitive neuroscience and neuroimaging · 2022Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Docosahexaenoic acid (22:6n-3) is the major brain n-3 polyunsaturated fatty acid and it is possible that docosahexaenoic acid is anti-inflammatory in the brain as it is known to be in other tissues. Using a combination of models including the fat-1 transgenic mouse, chronic dietary n-3 polyunsaturated fatty acid modulation in transgenic and wild-type mice, and acute direct brain infusion, we demonstrated that unesterified docosahexaenoic acid attenuates neuroinflammation initiated by intracerebroventricular lipopolysaccharide. Hippocampal neuroinflammation was assessed by gene expression and immunohistochemistry. Furthermore, docosahexaenoic acid protected against lipopolysaccharide-induced neuronal loss. Acute intracerebroventricular infusion of unesterified docosahexaenoic acid or its 12/15-lipoxygenase product and precursor to protectins and resolvins, 17S-hydroperoxy-docosahexaenoic acid, mimics anti-neuroinflammatory aspects of chronically increased unesterified docosahexaenoic acid. LC-MS/MS revealed that neuroprotectin D1 and several other docosahexaenoic acid-derived specialized pro-resolving mediators are present in the hippocampus. Acute intracerebroventricular infusion of 17S-hydroperoxy-docosahexaenoic acid increases hippocampal neuroprotectin D1 levels concomitant to attenuating neuroinflammation. These results show that unesterified docosahexaenoic acid is protective in a lipopolysaccharide-initiated mouse model of acute neuroinflammation, at least in part, via its conversion to specialized pro-resolving mediators; these docosahexaenoic acid stores may provide novel targets for the prevention and treatment(s) of neurological disorders with a neuroinflammatory component. Our study shows that chronically increased brain unesterified DHA levels, but not solely phospholipid DHA levels, attenuate neuroinflammation. Similar attenuations occur with acute increases in brain unesterified DHA or 17S-HpDHA levels, highlighting the importance of an available pool of precursor unesterified DHA for the production of enzymatically derived specialized pro-resolving mediators that are critical in the regulation of neuroinflammation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.