抗 NMDA 受体脑炎患者脑脊液抑制突触可塑性。

Suppression of synaptic plasticity by cerebrospinal fluid from anti-NMDA receptor encephalitis patients.

机构信息

Department of Physiology, Kanazawa Medical University, Ishikawa, Japan.

出版信息

Neurobiol Dis. 2012 Jan;45(1):610-5. doi: 10.1016/j.nbd.2011.09.019. Epub 2011 Oct 8.

DOI:10.1016/j.nbd.2011.09.019

PMID:22008231

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

我们通过使用小鼠海马脑片来评估抗 N-甲基-D-天冬氨酸受体（NMDAR）脑炎患者的脑脊液（CSF）对 NMDAR 介导的突触可塑性的功能影响。通过免疫染色重组 NMDAR 异聚体在 HEK 细胞培养物中的表达以及培养的海马神经元中的天然 NMDAR，建立了抗 NMDAR 抗体检测系统。在对临床信息完全不了解的情况下，对 36 名预先诊断的患者的 CSF 和血清进行了抗 NMDAR 抗体检测。通过该检测，有 13 名患者被诊断为抗 NMDAR 脑炎。CSF 中的抗 NMDAR 抗体抑制了小鼠海马脑片中 Schaffer 侧枝-CA1 突触的长时程增强（LTP）诱导。CSF 取自单纯疱疹病毒（HSV）脑炎或非脑炎对照组患者时，不会抑制 LTP 的诱导。用表达 NMDAR 的 HEK 细胞培养物进行抗体吸收可逆转抗 NMDAR 脑炎患者 CSF 对 LTP 的抑制作用，证实抗 NMDAR 抗体抑制了 LTP。本实验有力地支持了这样的观点，即抗 NMDAR 脑炎自身抗体是导致该疾病伴随的记忆障碍等认知障碍的原因。