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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Nature Portfolio
2021-01-01
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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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language | English |
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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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