Modulation of the primary astrocyte-enriched cultures’ oxylipin profiles reduces neurotoxicity

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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Authors
Guryleva M.V.1 , Chistyakov D.V. 2 , Lopachev A.V. 3 , Goriainov S.V. 4 , Astakhova A.A.2 , Timoshina Y.A.3, 5 , Khutorova A.V.3, 5 , Fedorova T.N. 3 , Sergeeva M.G. 2
Journal
Publisher
MDPI AG
Number of issue
8
Language
English
Status
Published
Number
498
Volume
11
Year
2021
Organizations
  • 1 Faculty of Bioengineering and Bioinformatics, Moscow Lomonosov State University, Moscow, 119234, Russian Federation
  • 2 Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russian Federation
  • 3 Laboratory of Clinical and Experimental Neurochemistry, Research Center of Neurology, Moscow, 125367, Russian Federation
  • 4 SREC PFUR, Peoples’ Friendship University of Russia (RUDN University), Moscow, 117198, Russian Federation
  • 5 Biological Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation
Keywords
Astrocytes; ERK1/2; Interleukin 10 (IL-10); Interleukin 6 (IL-6); Lipoxygenases; ML355; Neuroinflammation; Neurons; Neurotoxicity; Oxylipins; Toll-like receptors (TLRs); Zileuton
Date of creation
16.12.2021
Date of change
16.12.2021
Short link
https://repository.rudn.ru/en/records/article/record/76716/
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