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Mol Neurobiol. 2019 Nov 1. doi: 10.1007/s12035-019-01805-4. [Epub ahead of print]

Effects of Docosahexaenoic Acid and Its Peroxidation Product on Amyloid-β Peptide-Stimulated Microglia.

Author information

1
Richard and Loan Hill Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, 60607, USA.
2
Department of Chemistry, University of Missouri, Columbia, MO, 65211, USA.
3
Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA.
4
Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, 60612, USA.
5
Richard and Loan Hill Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, 60607, USA. LeeJam@uic.edu.
6
UIC Bioengineering (MC 063), 851 S Morgan St., 218 SEO, Chicago, IL, 60607, USA. LeeJam@uic.edu.

Abstract

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 A2 (p-cPLA2), 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).

KEYWORDS:

Alzheimer’s disease; Fish oil; Lipid peroxidation; Omega-3 fatty acids; Phospholipase A2

PMID:
31677009
DOI:
10.1007/s12035-019-01805-4

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