N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats

Abstract At present, there is a growing interest in the study of the neurotropic activity of polyunsaturated fatty acids ethanolamides (N-acylethanolamines). N-docosahexaenoylethanolamine (DHEA, synaptamide) is an endogenous metabolite and structural analogue of anandamide, a widely studied endocann...

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Main Authors: Arina I. Ponomarenko, Anna A. Tyrtyshnaia, Evgeny A. Pislyagin, Inessa V. Dyuizen, Ruslan M. Sultanov, Igor V. Manzhulo
Format: Article
Language:English
Published: Nature Portfolio 2021-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-80818-9
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author Arina I. Ponomarenko
Anna A. Tyrtyshnaia
Evgeny A. Pislyagin
Inessa V. Dyuizen
Ruslan M. Sultanov
Igor V. Manzhulo
author_facet Arina I. Ponomarenko
Anna A. Tyrtyshnaia
Evgeny A. Pislyagin
Inessa V. Dyuizen
Ruslan M. Sultanov
Igor V. Manzhulo
author_sort Arina I. Ponomarenko
collection DOAJ
description Abstract At present, there is a growing interest in the study of the neurotropic activity of polyunsaturated fatty acids ethanolamides (N-acylethanolamines). N-docosahexaenoylethanolamine (DHEA, synaptamide) is an endogenous metabolite and structural analogue of anandamide, a widely studied endocannabinoid derived from arachidonic acid. The results of this study demonstrate that DHEA, when administered subcutaneously (10 mg/kg/day, 7 days), promotes cognitive recovery in rats subjected to mild traumatic brain injury (mTBI). In the cerebral cortex of experimental animals, we analyzed the dynamics of Iba-1-positive microglia activity changes and the expression of pro-inflammatory markers (IL1β, IL6, CD86). We used immortalized mouse microglial cells (SIM-A9) to assess the effects of DHEA on LPS-induced cytokines/ROS/NO/nitrite, as well as on CD206 (anti-inflammatory microglia) and the antioxidant enzyme superoxide dismutase (SOD) production. In vivo and in vitro experiments showed that DHEA: (1) improves indicators of anxiety and long-term memory; (2) inhibits the pro-inflammatory microglial cells activity; (3) decrease the level of pro-inflammatory cytokines/ROS/NO/nitrites; (4) increase CD206 and SOD production. In general, the results of this study indicate that DHEA has a complex effect on the neuroinflammation processes, which indicates its high therapeutic potential.
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spelling doaj.art-34d6c21ccf6c4caa8e88f516cc1c347a2022-12-21T21:35:45ZengNature PortfolioScientific Reports2045-23222021-01-0111111210.1038/s41598-020-80818-9N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in ratsArina I. Ponomarenko0Anna A. Tyrtyshnaia1Evgeny A. Pislyagin2Inessa V. Dyuizen3Ruslan M. Sultanov4Igor V. Manzhulo5A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of SciencesA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of SciencesG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of SciencesA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of SciencesA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of SciencesA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of SciencesAbstract At present, there is a growing interest in the study of the neurotropic activity of polyunsaturated fatty acids ethanolamides (N-acylethanolamines). N-docosahexaenoylethanolamine (DHEA, synaptamide) is an endogenous metabolite and structural analogue of anandamide, a widely studied endocannabinoid derived from arachidonic acid. The results of this study demonstrate that DHEA, when administered subcutaneously (10 mg/kg/day, 7 days), promotes cognitive recovery in rats subjected to mild traumatic brain injury (mTBI). In the cerebral cortex of experimental animals, we analyzed the dynamics of Iba-1-positive microglia activity changes and the expression of pro-inflammatory markers (IL1β, IL6, CD86). We used immortalized mouse microglial cells (SIM-A9) to assess the effects of DHEA on LPS-induced cytokines/ROS/NO/nitrite, as well as on CD206 (anti-inflammatory microglia) and the antioxidant enzyme superoxide dismutase (SOD) production. In vivo and in vitro experiments showed that DHEA: (1) improves indicators of anxiety and long-term memory; (2) inhibits the pro-inflammatory microglial cells activity; (3) decrease the level of pro-inflammatory cytokines/ROS/NO/nitrites; (4) increase CD206 and SOD production. In general, the results of this study indicate that DHEA has a complex effect on the neuroinflammation processes, which indicates its high therapeutic potential.https://doi.org/10.1038/s41598-020-80818-9
spellingShingle Arina I. Ponomarenko
Anna A. Tyrtyshnaia
Evgeny A. Pislyagin
Inessa V. Dyuizen
Ruslan M. Sultanov
Igor V. Manzhulo
N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats
Scientific Reports
title N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats
title_full N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats
title_fullStr N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats
title_full_unstemmed N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats
title_short N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats
title_sort n docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats
url https://doi.org/10.1038/s41598-020-80818-9
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