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.
华中科技大学同济医学院附属协和医院，日本石川县金泽医科大学医学研究所
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：
采用小鼠的海马切片，评估了抗 NMDAR 脑炎患者的脑脊液对 NMDA 介导的突触可塑性功能上的影响。通过对培养的 HEK 细胞中表达的 NMDAR 重组体及在培养的海马神经元中天然的 NMDARs 进行免疫染色，建立了抗 NMADR 抗体检测系统。在对临床信息盲态的情况下，诊断前收集了 36 例患者的脑脊液和血样以来检测抗 NMDAR 抗体。借助该检测，13 例患者被诊断出抗 NMDAR 脑炎。在小鼠海马切片中，抗 NMDAR 抗体阳性的脑脊液抑制 Schaffer 侧枝 -CA1 突触的长时程增程诱导（LTP）。在单纯疱疹病毒脑炎及无脑炎的对照患者中，LTP 诱导没有被抑制。对培养的表达 NMDAR 的 HEK 细胞进行抗体吸附，可以逆转抗 NMDAR 脑炎患者脑脊液对 LTP 的抑制，这肯定了抗 NMDAR 抗体抑制 LTP。像脑炎伴随的失忆这样的认知障碍，抗 NMDAR 脑炎的自身抗体在其中起了重要的作用，目前的试验强有力地支持了这一点。
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