Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity
Open Access
- 30 July 2021
- journal article
- research article
- Published by MDPI AG in Metabolites
- Vol. 11 (8), 498
- https://doi.org/10.3390/metabo11080498
Abstract
Recently, manipulations with reactive astrocytes have been viewed as a new therapeutic approach that will enable the development of treatments for acute brain injuries and neurodegenerative diseases. Astrocytes can release several substances, which may exert neurotoxic or neuroprotective effects, but the nature of these substances is still largely unknown. In the present work, we tested the hypothesis that these effects may be attributed to oxylipins, which are synthesized from n-3 or n-6 polyunsaturated fatty acids (PUFAs). We used astrocyte-enriched cultures and found that: (1) lipid fractions secreted by lipopolysaccharide (LPS)—stimulated rat primary astrocyte-enriched cultures—possessed neurotoxic activity in rat primary neuronal cultures; (2) both of the tested oxylipin synthesis inhibitors, ML355 and Zileuton, reduce the LPS-stimulated release of interleukin 6 (IL-6) by astrocyte cultures, but only ML355 can change lipid fractions from neurotoxic to non-toxic; and (3) oxylipin profiles, measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) from neurotoxic and non-toxic lipid fractions, reveal a group of n-3 docosahexaenoic acid derivatives, hydroxydocosahexaenoic acids (HdoHEs)-4-HdoHE, 8-HdoHE, and 17-HdoHE, which may reflect the neuroprotective features of lipid fractions. Regulating the composition of astrocyte oxylipin profiles may be suggested as an approach for regulation of neurotoxicity in inflammatory processes.Funding Information
- Russian Foundation for Basic Research (19-29-01243)
This publication has 52 references indexed in Scilit:
- Astrocytes, but Not Microglia, Rapidly Sense H2O2 via STAT6 Phosphorylation, Resulting in Cyclooxygenase-2 Expression and Prostaglandin ReleaseThe Journal of Immunology, 2012
- Genomic Analysis of Reactive AstrogliosisJournal of Neuroscience, 2012
- Development of a Method for the Purification and Culture of Rodent AstrocytesNeuron, 2011
- Thrombin-activated human platelets acutely generate oxidized docosahexaenoic-acid-containing phospholipids via 12-lipoxygenaseBiochemical Journal, 2010
- The 5‐lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophagesBritish Journal of Pharmacology, 2010
- Purity, cell viability, expression of GFAP and bystin in astrocytes cultured by different proceduresJournal of Cellular Biochemistry, 2009
- Novel lipoxygenase inhibitors as neuroprotective reagentsJournal of Neuroscience Research, 2007
- Microglial cells in astroglial cultures: a cautionary noteJournal of Neuroinflammation, 2007
- Prostaglandin D2 mediates neuronal protection via the DP1 receptorJournal of Neurochemistry, 2004
- Prostaglandin E2 induced caspase-dependent apoptosis possibly through activation of EP2 receptors in cultured hippocampal neuronsNeurochemistry International, 2004