Tyrtyshnaia Anna A, Manzhulo Igor V, Sultanov Ruslan M, Ermolenko Ekaterina V
National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Palchevskogo Str, 17, Vladivostok, 690041, Russian Federation; School of Biomedicine, Far Eastern Federal University, Sukhanova 8, Vladivostok, 690091, Russian Federation.
National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Palchevskogo Str, 17, Vladivostok, 690041, Russian Federation.
Acta Histochem. 2017 Oct;119(8):812-821. doi: 10.1016/j.acthis.2017.10.007. Epub 2017 Oct 26.
Neuropathic pain manifested by a number of sensory symptoms is often accompanied by disorders of higher nervous activity, such as memory impairment, depression, anxiety, anhedonia, etc. This emphasizes the involvement of supraspinal structures including the hippocampus in neuropathic pain pathogenesis. In the present study, we focused on the impact of chronic neuropathic pain on hippocampal neurogenesis and microglial state. In addition, we test the effect of alkyl glycerol ethers on hippocampal neuronal and microglial plasticity as well as behavioral parameters. Neuropathic pain was induced using the model of sciatic nerve chronic constriction injury. We found an impairment of working memory and locomotor activity in animals with neuropathic pain, which was prevented by alkyl glycerol ethers treatment. Sciatic nerve ligation in mice contributed to the decrease in hippocampal neurogenesis intensity. Alkyl glycerol ethers administration significantly reduced this effect. Neuropathic pain-associated neurogenesis reduction was accompanied by an increased percentage of Iba1-labeled area in the CA1 hippocampal region on the 14th and 28th days after surgery. In addition, we observed a decrease in hippocampal pro-inflammatory microglia marker CD86 immunostaining on day 28 after surgery in alkyl glycerol ethers-treated mice with sciatic nerve ligation. These results are consistent with data on pro- and anti-inflammatory cytokines expression in the hippocampus. Alkyl glycerol ethers administration increased IL-10 and decreased IL-1β hippocampal expression in animals with neuropathic pain. Taken together, these data suggest that neuropathic pain-behavior in rodents is accompanied by changes in microglia polarization, thereby contributing to neurogenesis impairment and cognitive disturbances. Alkyl glycerol ethers prevented M1 microglial activation, contributing to the maintenance of normal neurogenesis levels within the hippocampus and normalizing working memory.
由多种感觉症状表现出的神经性疼痛通常伴有高级神经活动障碍，如记忆障碍、抑郁、焦虑、快感缺失等。这强调了包括海马体在内的脊髓上结构参与了神经性疼痛的发病机制。在本研究中，我们聚焦于慢性神经性疼痛对海马体神经发生和小胶质细胞状态的影响。此外，我们测试了烷基甘油醚对海马体神经元和小胶质细胞可塑性以及行为参数的影响。使用坐骨神经慢性压迫损伤模型诱导神经性疼痛。我们发现患有神经性疼痛的动物存在工作记忆和运动活动受损，而烷基甘油醚治疗可预防这种情况。小鼠坐骨神经结扎导致海马体神经发生强度降低。给予烷基甘油醚可显著减轻这种作用。与神经性疼痛相关的神经发生减少伴随着术后第14天和第28天海马体CA1区Iba1标记区域百分比增加。此外，我们观察到在接受烷基甘油醚治疗的坐骨神经结扎小鼠术后第28天，海马体促炎小胶质细胞标志物CD86免疫染色减少。这些结果与海马体中促炎和抗炎细胞因子表达的数据一致。给予烷基甘油醚可增加患有神经性疼痛动物海马体中IL - 10的表达并降低IL - 1β的表达。综上所述，这些数据表明啮齿动物的神经性疼痛行为伴随着小胶质细胞极化的变化，从而导致神经发生受损和认知障碍。烷基甘油醚可防止M1小胶质细胞活化，有助于维持海马体内正常的神经发生水平并使工作记忆正常化。
