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。
