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Open AccessArticle

N-Docosahexaenoylethanolamine Attenuates Neuroinflammation and Improves Hippocampal Neurogenesis in Rats with Sciatic Nerve Chronic Constriction Injury

A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Palchevs.kogo Str, 17, 690041 Vladivostok, Russia
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Mar. Drugs 2020, 18(10), 516; https://doi.org/10.3390/md18100516
Received: 1 September 2020 / Revised: 10 October 2020 / Accepted: 13 October 2020 / Published: 15 October 2020
(This article belongs to the Special Issue Marine Compounds from the Far Eastern Organisms)
Chronic neuropathic pain is a condition that causes both sensory disturbances and a variety of functional disorders, indicating the involvement of various brain structures in pain pathogenesis. One of the factors underlying chronic neuropathic pain is neuroinflammation, which is accompanied by microglial activation and pro-inflammatory factor release. N-docosahexaenoylethanolamine (DHEA, synaptamide) is an endocannabinoid-like metabolite synthesized endogenously from docosahexaenoic acid. Synaptamide exhibits anti-inflammatory activity and improves neurite outgrowth, neurogenesis, and synaptogenesis within the hippocampus. This study aims to evaluate the effects of synaptamide obtained by the chemical modification of DHA, extracted from the Far Eastern raw material Berryteuthis magister on neuroinflammatory response and hippocampal neurogenesis changes during neuropathic pain. The study of microglial protein and cytokine concentrations was performed using immunohistochemistry and ELISA. The brain lipid analysis was performed using the liquid chromatography-mass spectrometry technique. Behavioral experiments showed that synaptamide prevented neuropathic pain-associated sensory and behavioral changes, such as thermal allodynia, impaired locomotor activity, working and long-term memory, and increased anxiety. Synaptamide attenuated microglial activation, release of proinflammatory cytokines, and decrease in hippocampal neurogenesis. Lipid analysis revealed changes in the brain N-acylethanolamines composition and plasmalogen concentration after synaptamide administration. In conclusion, we show here that synaptamide may have potential for use in preventing or treating neuropathic cognitive pain and emotional effects. View Full-Text
Keywords: N-docosahexaenoylethanolamine; DHEA; synaptamide; hippocampus; neuropathic pain; microglia; chronic constriction injury; neurogenesis N-docosahexaenoylethanolamine; DHEA; synaptamide; hippocampus; neuropathic pain; microglia; chronic constriction injury; neurogenesis
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Tyrtyshnaia, A.A.; Egorova, E.L.; Starinets, A.A.; Ponomarenko, A.I.; Ermolenko, E.V.; Manzhulo, I.V. N-Docosahexaenoylethanolamine Attenuates Neuroinflammation and Improves Hippocampal Neurogenesis in Rats with Sciatic Nerve Chronic Constriction Injury. Mar. Drugs 2020, 18, 516.

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