Open AccessEffects of Docosahexaenoic Acid and Its Peroxidation Product on Amyloid-β Peptide-Stimulated Microglia
Author(s) -
Xin Geng,
Bo Yang,
Yuanli Zhao,
Tao Teng,
Mary Jo LaDu,
Grace Y. Sun,
C. Michael Greenlief,
James C.-M. Lee
Publication year - 2019
Publication title -
molecular neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.569
H-Index - 111
eISSN - 1559-1182
pISSN - 0893-7648
DOI - 10.1007/s12035-019-01805-4
Subject(s) - microglia , docosahexaenoic acid , neuroprotection , chemistry , oxidative stress , reactive oxygen species , neurodegeneration , lipid peroxidation , arachidonic acid , phospholipase a2 , biochemistry , nitric oxide , amyloid beta , tumor necrosis factor alpha , pharmacology , microbiology and biotechnology , endocrinology , inflammation , medicine , biology , immunology , peptide , polyunsaturated fatty acid , fatty acid , enzyme , disease , organic chemistry
Growing evidence suggests that docosahexaenoic acid (DHA) exerts neuroprotective effects, although the mechanism(s) underlying these beneficial effects are not fully understood. Here we demonstrate that DHA, but not arachidonic acid (ARA), suppressed oligomeric amyloid-β peptide (oAβ)-induced reactive oxygen species (ROS) production in primary mouse microglia and immortalized mouse microglia (BV2). Similarly, DHA but not ARA suppressed oAβ-induced increases in phosphorylated cytosolic phospholipase A 2 (p-cPLA 2 ), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) in BV2 cells. LC-MS/MS assay indicated the ability for DHA to cause an increase in 4-hydroxyhexenal (4-HHE) and suppress oAβ-induced increase in 4-hydroxynonenal (4-HNE). Although oAβ did not alter the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, exogenous DHA, ARA as well as low concentrations of 4-HHE and 4-HNE upregulated this pathway and increased production of heme oxygenase-1 (HO-1) in microglial cells. These results suggest that DHA modulates ARA metabolism in oAβ-stimulated microglia through suppressing oxidative and inflammatory pathways and upregulating the antioxidative stress pathway involving Nrf2/HO-1. Understanding the mechanism(s) underlying the beneficial effects of DHA on microglia should shed light into nutraceutical therapy for the prevention and treatment of Alzheimer's disease (AD).