抗NMDA受體腦炎患者的腦脊液對突觸可塑性的抑制

07-27

Neurobiol Dis 2012 Jan;45 (1): 610-5. [IF:5.121] Suppression of synaptic plasticity by cerebrospinal fluid from anti-NMDA receptor encephalitis patients. Zhang Q , Tanaka K , Sun P , Nakata M , Yamamoto R , Sakimura K , Matsui M , Kato N . Department of Physiology, Kanazawa Medical University, Ishikawa, Japan; Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 華中科技大學同濟醫學院附屬協和醫院，日本石川縣金澤醫科大學醫學研究所

Abstract The functional effects of cerebrospinal fluid (CSF) from patients with anti-NMDA receptor (NMDAR) encephalitis on the NMDAR-mediated synaptic plasticity were evaluated by using mouse hippocampus slices. Anti-NMDAR antibody detection system was established by immunostaining recombinant NMDAR heteromers expressed in HEK cell culture as well as native NMDARs in cultured hippocampal neurons. Under a complete blind manner for the clinical information, CSF and sera collected from 36 pre-diagnosed patients were tested for anti-NMDAR antibodies. With this test, thirteen patients were diagnosed as anti-NMDAR encephalitis. CSF positive for anti-NMDAR antibodies suppressed induction of long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in mouse hippocampal slices. LTP induction was not suppressed by CSF collected from herpes simplex virus (HSV) encephalitis or non-encephalitis control patients. Antibody absorption with NMDAR-expressing HEK cell culture reversed the suppression of LTP by anti-NMDAR encephalitis patients" CSF, confirming that anti-NMDAR antibodies suppressed LTP. The present experiments firmly support the proposal that the anti-NMDAR encephalitis autoantibody is responsible for cognitive disorders like amnesia accompanying this disease.

摘要：採用小鼠的海馬切片，評估了抗 NMDAR 腦炎患者的腦脊液對 NMDA 介導的突觸可塑性功能上的影響。通過對培養的 HEK 細胞中表達的 NMDAR 重組體及在培養的海馬神經元中天然的 NMDARs 進行免疫染色，建立了抗 NMADR 抗體檢測系統。在對臨床信息盲態的情況下，診斷前收集了 36 例患者的腦脊液和血樣以來檢測抗 NMDAR 抗體。藉助該檢測，13 例患者被診斷出抗 NMDAR 腦炎。在小鼠海馬切片中，抗 NMDAR 抗體陽性的腦脊液抑制 Schaffer 側枝 -CA1 突觸的長時程增程誘導（LTP）。在單純皰疹病毒腦炎及無腦炎的對照患者中，LTP 誘導沒有被抑制。對培養的表達 NMDAR 的 HEK 細胞進行抗體吸附，可以逆轉抗 NMDAR 腦炎患者腦脊液對 LTP 的抑制，這肯定了抗 NMDAR 抗體抑制 LTP。像腦炎伴隨的失憶這樣的認知障礙，抗 NMDAR 腦炎的自身抗體在其中起了重要的作用，目前的試驗強有力地支持了這一點。

編輯：秀秀