Manzhulo Igor, Manzhulo Olga, Tyrtyshnaia Anna, Ponomarenko Arina, Konovalova Sophia, Ermolenko Ekaterina, Milkina Elena, Starinets Anna
A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, Russia.
Brain Sci. 2021 Nov 26;11(12):1561. doi: 10.3390/brainsci11121561.
The present study demonstrates that synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of docosahexaenoic acid, when administered subcutaneously (4 mg/kg/day, 14 days), exhibits analgesic activity and promotes cognitive recovery in the rat sciatic nerve chronic constriction injury (CCI) model. We analyzed the dynamics of GFAP-positive astroglia and S100β-positive astroglia activity, the expression of nerve growth factor (NGF), and two subunits of the NMDA receptor (NMDAR1 and NMDAR2A) in the hippocampi of the experimental animals. Hippocampal neurogenesis was evaluated by immunohistochemical detection of DCX. Analysis of N-acylethanolamines in plasma and in the brain was performed using the liquid chromatography-mass spectrometry technique. In vitro and in vivo experiments show that synaptamide (1) reduces cold allodynia, (2) improves working memory and locomotor activity, (3) stabilizes neurogenesis and astroglial activity, (4) enhances the expression of NGF and NMDAR1, (5) increases the concentration of Ca in astrocytes, and (6) increases the production of N-acylethanolamines. The results of the present study demonstrate that synaptamide affects the activity of hippocampal astroglia, resulting in faster recovery after CCI.
本研究表明，二十二碳六烯酸的内源性代谢产物突触酰胺（N-二十二碳六烯酰乙醇胺），皮下给药（4毫克/千克/天，14天）时，在大鼠坐骨神经慢性压迫损伤（CCI）模型中表现出镇痛活性并促进认知恢复。我们分析了实验动物海马中GFAP阳性星形胶质细胞和S100β阳性星形胶质细胞活性的动态变化、神经生长因子（NGF）的表达以及NMDA受体的两个亚基（NMDAR1和NMDAR2A）。通过免疫组织化学检测双皮质素（DCX）评估海马神经发生。使用液相色谱-质谱技术分析血浆和脑中的N-酰基乙醇胺。体外和体内实验表明，突触酰胺（1）减轻冷觉异常性疼痛，（2）改善工作记忆和运动活动，（3）稳定神经发生和星形胶质细胞活性，（4）增强NGF和NMDAR1的表达，（5）增加星形胶质细胞中钙的浓度，以及（6）增加N-酰基乙醇胺的产生。本研究结果表明，突触酰胺影响海马星形胶质细胞的活性，从而在CCI后实现更快的恢复。
