title: [Clinical profiles of Japanese patients with anti-NMDAR encephalitis and functional analysis of the anti-NMDAR antibodies].
abstract: The N-methyl-D-aspartate receptor (NMDAR) encephalitis is characterized by a set of neurologic and psychiatric symptoms including seizures. Early removal of the antibodies ameliorate the disease course and the antibodies are thought to relate closely to its symptoms. We tested the anti-NMDAR antibodies with cell-based assay using NMDAR NR1/NR2 heteromers expressed on HEK cells and found 41 antibody-positive cases from 2008 to 2011. Most of them showed typical clinical features as described, however, some show schizophrenia-like symptoms or chronic epilepsy. The NMDAR is essential both for memory and synaptic plasticity, most notably expressed as long-term potentiation (LTP). The binding of antibody is shown to dimerize NMDARs and trigger their internalization on the postsynaptic site, thereby suppressing NMDAR-mediated transmission. Despite such molecular understanding, it is not known whether the antibody-mediated dysfunction of NMDARs underlies the symptoms of the anti-NMDAR encephalitis. We tested whether the disease-produced antibodies suppress NMDAR-dependent LTP induction, and found the CSF positive for anti-NMDAR antibodies suppressed induction of LTP at CA1 synapses in mouse hippocampal slices. Antibody absorption with NR1 antigens reversed the suppression of LTP, confirming that anti-NMDAR antibodies specifically suppressed LTP. The present experiments firmly support the proposal that the anti-NMDAR antibody is responsible for cognitive disorders like amnesia accompanying with this disease.
authors.affiliation: Department of Neurology, Medical Research Institute, Kanazawa Medical University.
authors.forename: Keiko
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000818:Animals; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate