title: Stereotactic injection of cerebrospinal fluid from anti-NMDA receptor encephalitis into rat dentate gyrus impairs NMDA receptor function.
abstract: Autoimmune encephalitis is increasingly recognized in patients with otherwise unexplained encephalopathy with epilepsy. Among these, patients with anti-N-methyl D-aspartate receptor (NMDAR) encephalitis present epileptic seizures, memory deficits, and psychiatric symptoms. However, the functional consequences of such autoantibodies are poorly understood. In order to investigate the pathophysiology of this disease, we stereotactically injected either cerebrospinal fluid (CSF) from three anti-NMDAR encephalitis patients or commercially available anti-NMDAR1 into the dentate gyrus of adult female rats. Control animals were injected with either CSF obtained from three epilepsy patients (ganglioglioma, posttraumatic epilepsy, focal cortical dysplasia) lacking anti-NMDAR or saline. Intracellular recordings from dentate gyrus granule cells showed a significant reduction of the NMDAR-evoked excitatory postsynaptic potentials (NMDAR-EPSPs) in animals treated with anti-NMDAR. As a consequence of this, action potential firing in these cells by NMDAR-EPSPs was significantly impaired. Long-term potentiation in the dentate gyrus was also significantly reduced in rats injected with anti-NMDAR as compared to control animals. This was accompanied by a significantly impaired learning performance in the Morris water maze hidden platform task when the animals had been injected with anti-NMDAR antibody-containing CSF. Our findings suggest that anti-NMDAR lead to reduced NMDAR function in vivo which could contribute to the memory impairment found in patients with anti-NMDAR encephalitis.
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Würdemann
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Germany.
authors.forename: Maxi
authors.initials: M
authors.lastname: Kersten
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Germany.
authors.forename: Tursonjan
authors.initials: T
authors.lastname: Tokay
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Germany.
authors.forename: Xiati
authors.initials: X
authors.lastname: Guli
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Kober
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Porath
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Sellmann
authors.affiliation: Mara Clinic, Bielefeld, Germany.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bien
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Köhling
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Germany. Electronic address: timo.kirschstein@uni-rostock.de.
authors.forename: Timo
authors.initials: T
authors.lastname: Kirschstein
mesh_terms: D000328:Adult; D000818:Animals; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000134:cerebrospinal fluid / Q000150:complications*; D001323:Autoantibodies / Q000008:administration & dosage*; D018891:Dentate Gyrus / Q000187:drug effects*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D013238:Stereotaxic Techniques
chemical_list: D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate
keywords: AMPA receptor; CNQX; GABA(A) receptor; LTP; NR1; SR95531