Wang Xu, Ma Chi, Liu Cai-Yun, Li Guang-Jian, Zhao Ding, Han Dong-Feng
Department of Neurology and Neuroscience Center, First Hospital of Jilin University, Changchun, China.
Department of Neurosurgery, First Hospital of Jilin University, Changchun, China.
Front Neurol. 2019 Jun 26;10:684. doi: 10.3389/fneur.2019.00684. eCollection 2019.
Among autoimmune encephalitis, patients with anti-N-methyl D- aspartate receptor (NMDAR) encephalitis typically present epileptic seizures, memory deficits and psychiatric symptoms. However, the signal mechanisms leading to the functional disorders of autoantibodies are largely unclear. In this study, anti-NMDAR antibody was administered into dentate gyri against the NR1 subunit of the NMDAR. The purpose of the study examined the effects of pro-inflammatory tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) on neuronal NMDAR currents of the hippocampus in rats with anti-NMDAR encephalitis and we further determined the role played by TNF-α and IL-6 in modulating learning performance. In results, we observed a decrease in amplitude of the NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs) in the hippocampal neurons of animals treated with anti-NMDAR. In those rats with anti-NMDAR, we also observed impaired learning performance in the Morris water maze and spatial working memory test. Of note, cerebral infusion of TNF-α and IL-6 worsened NMDAR-EPSCs and this was accompanied with exaggeration of impaired learning performance. In conclusion, our findings suggest that the role played by neuroinflammation in exacerbating the memory impairment found in animals treated with anti-NMDAR. Anti-inflammation is a potential target in improving the memory impairment induced by anti-NMDA encephalitis.
在自身免疫性脑炎中，抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎患者通常会出现癫痫发作、记忆缺陷和精神症状。然而，导致自身抗体功能障碍的信号机制在很大程度上尚不清楚。在本研究中，将抗NMDAR抗体注射到齿状回中，针对NMDAR的NR1亚基。该研究的目的是检测促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）对患有抗NMDAR脑炎大鼠海马神经元NMDAR电流的影响，并进一步确定TNF-α和IL-6在调节学习能力方面所起的作用。结果显示，在用抗NMDAR处理的动物海马神经元中，我们观察到NMDAR介导的兴奋性突触后电流（NMDAR-EPSCs）的幅度降低。在那些患有抗NMDAR的大鼠中，我们还观察到在莫里斯水迷宫和空间工作记忆测试中学习能力受损。值得注意的是，向大脑中注入TNF-α和IL-6会使NMDAR-EPSCs恶化，并伴有学习能力受损的加剧。总之，我们的研究结果表明，神经炎症在加重抗NMDAR处理动物的记忆损伤中所起的作用。抗炎是改善抗NMDA脑炎所致记忆损伤的一个潜在靶点。
