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- Title
Modulation of the Primary Astrocyte-Enriched Cultures' Oxylipin Profiles Reduces Neurotoxicity.
- Authors
Guryleva, Mariia V.; Chistyakov, Dmitry V.; Lopachev, Alexander V.; Goriainov, Sergei V.; Astakhova, Alina A.; Timoshina, Yulia A.; Khutorova, Anastasiya V.; Fedorova, Tatiana N.; Sergeeva, Marina G.
- 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.
- Subjects
OMEGA-6 fatty acids; LIQUID chromatography-mass spectrometry; ASTROCYTES; UNSATURATED fatty acids; THERAPEUTICS; NEUROTOXICOLOGY
- Publication
Metabolites (2218-1989), 2021, Vol 11, Issue 8, p498
- ISSN
2218-1989
- Publication type
Article
- DOI
10.3390/metabo11080498