He Shuyu, Sun Chongyang, Zhu Qian, Li Lin, Huang Jianyu, Wu Ge, Cao Yi, Liao Jianxiang, Lu Yi, Su Qiru, Lin Sufang, Ma Xiaopeng, Zhong Cheng
Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institution, Shenzhen, China.
Department of Clinical Research, Department of Neurology, Surgery Division, Epilepsy Center, Shenzhen Children's Hospital, Shenzhen, China.
Front Mol Neurosci. 2023 Sep 18;16:1211119. doi: 10.3389/fnmol.2023.1211119. eCollection 2023.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a common autoimmune encephalitis, and it is associated with psychosis, dyskinesia, and seizures. Anti-NMDAR encephalitis (NMDARE) in juveniles and adults presents different clinical charactreistics. However, the pathogenesis of juvenile anti-NMDAR encephalitis remains unclear, partly because of a lack of suitable animal models.
We developed a model of juvenile anti-NMDAR encephalitis using active immunization with an amino terminal domain peptide from the GluN1 subunit (GluN1) against NMDARs in 3-week-old female C57BL/6J mice.
Immunofluorescence staining suggested that autoantibody levels in the hippocampus increased, and HEK-293T cells staining identified the target of the autoantibodies as GluN1, suggesting that GluN1-specific immunoglobulin G was successfully induced. Behavior assessment showed that the mice suffered significant cognition impairment and sociability reduction, which is similar to what is observed in patients affected by anti-NMDAR encephalitis. The mice also exhibited impaired long-term potentiation in hippocampal CA1. Pilocarpine-induced epilepsy was more severe and had a longer duration, while no spontaneous seizures were observed.
The juvenile mouse model for anti-NMDAR encephalitis is of great importance to investigate the pathological mechanism and therapeutic strategies for the disease, and could accelerate the study of autoimmune encephalitis.
抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎是一种常见的自身免疫性脑炎，与精神病、运动障碍和癫痫发作有关。青少年和成人的抗NMDAR脑炎（NMDARE）表现出不同的临床特征。然而，青少年抗NMDAR脑炎的发病机制仍不清楚，部分原因是缺乏合适的动物模型。
我们通过用来自GluN1亚基（GluN1）的氨基末端结构域肽对3周龄雌性C57BL/6J小鼠进行主动免疫，建立了青少年抗NMDAR脑炎模型。
免疫荧光染色表明海马体中的自身抗体水平升高，HEK-293T细胞染色确定自身抗体的靶标为GluN1，这表明成功诱导了GluN1特异性免疫球蛋白G。行为评估显示，这些小鼠出现了明显的认知障碍和社交能力下降，这与抗NMDAR脑炎患者的情况相似。小鼠海马CA1区的长时程增强也受损。毛果芸香碱诱导的癫痫更严重且持续时间更长，同时未观察到自发性癫痫发作。
青少年抗NMDAR脑炎小鼠模型对于研究该疾病的病理机制和治疗策略具有重要意义，并且可以加速自身免疫性脑炎的研究。
