A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, Russia.
Int J Mol Sci. 2023 Mar 27;24(7):6273. doi: 10.3390/ijms24076273.
N-docosahexaenoylethanolamine (DHEA), or synaptamide, is an endogenous metabolite of docosahexaenoic acid (DHA) that exhibits synaptogenic and neurogenic effects. In our previous studies, synaptamide administration inhibited the neuropathic pain-like behavior and reduced inflammation in the central nervous system following sciatic nerve injury. In the present study, we examine the effect of synaptamide on the peripheral nervous system in a neuropathic pain condition. The dynamics of ionized calcium-binding adapter molecule 1 (iba-1), CD68, CD163, myelin basic protein, and the production of interleukin 1β and 6 within the sciatic nerve, as well as the neuro-glial index and the activity of iba-1, CD163, glial fibrillary acidic protein (GFAP), neuronal NO synthase (nNOS), substance P (SP), activating transcription factor 3 (ATF3) in the dorsal root ganglia (DRG), are studied. According to our results, synaptamide treatment (4 mg/kg/day) (1) decreases the weight-bearing deficit after nerve trauma; (2) enhances the remyelination process in the sciatic nerve; (3) shows anti-inflammatory properties in the peripheral nervous system; (4) decreases the neuro-glial index and GFAP immunoreactivity in the DRG; (5) inhibits nNOS- and SP-ergic activity in the DRG, which might contribute to neuropathic pain attenuation. In general, the current study demonstrates the complex effect of synaptamide on nerve injury, which indicates its high potential for neuropathic pain management.
N-二十二碳六烯酰乙醇胺（DHEA），又称神经酰胺，是二十二碳六烯酸（DHA）的内源性代谢产物，具有突触生成和神经生成作用。在我们之前的研究中，神经酰胺给药抑制了坐骨神经损伤后中枢神经系统的神经病理性疼痛样行为和炎症。在本研究中，我们研究了神经酰胺在神经病理性疼痛状态下对周围神经系统的影响。研究了坐骨神经中离子钙结合衔接分子 1（iba-1）、CD68、CD163、髓鞘碱性蛋白的动态变化，以及白细胞介素 1β和 6 的产生，以及神经胶质指数和iba-1、CD163、胶质纤维酸性蛋白（GFAP）、神经元一氧化氮合酶（nNOS）、P 物质（SP）在背根神经节（DRG）中的活性。根据我们的结果，神经酰胺治疗（4mg/kg/天）（1）减轻神经损伤后的负重缺陷；（2）增强坐骨神经中的髓鞘再生过程；（3）在周围神经系统中表现出抗炎特性；（4）降低 DRG 中的神经胶质指数和 GFAP 免疫反应性；（5）抑制 DRG 中的 nNOS 和 SP 能活性，这可能有助于减轻神经病理性疼痛。总的来说，本研究表明神经酰胺对神经损伤的复杂影响，表明其在神经病理性疼痛管理方面具有很高的潜力。
