Dataset Information

Selective Impairment of Spatial Cognition Caused by Autoantibodies to the N-Methyl-D-Aspartate Receptor.

ABSTRACT: Patients with systemic lupus erythematosus (SLE) experience cognitive abnormalities in multiple domains including processing speed, executive function, and memory. Here we show that SLE patients carrying antibodies that bind DNA and the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), termed DNRAbs, displayed a selective impairment in spatial recall. Neural recordings in a mouse model of SLE, in which circulating DNRAbs penetrate the hippocampus, revealed that CA1 place cells exhibited a significant expansion in place field size. Structural analysis showed that hippocampal pyramidal cells had substantial reductions in their dendritic processes and spines. Strikingly, these abnormalities became evident at a time when DNRAbs were no longer detectable in the hippocampus. These results suggest that antibody-mediated neurocognitive impairments may be highly specific, and that spatial cognition may be particularly vulnerable to DNRAb-mediated structural and functional injury to hippocampal cells that evolves after the triggering insult is no longer present.

SUBMITTER: Chang EH

PROVIDER: S-EPMC4534689 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Selective Impairment of Spatial Cognition Caused by Autoantibodies to the N-Methyl-D-Aspartate Receptor.

Chang Eric H EH Volpe Bruce T BT Mackay Meggan M Aranow Cynthia C Watson Philip P Kowal Czeslawa C Storbeck Justin J Mattis Paul P Berlin RoseAnn R Chen Huiyi H Mader Simone S Huerta Tomás S TS Huerta Patricio T PT Diamond Betty B

EBioMedicine 20150530 7

Patients with systemic lupus erythematosus (SLE) experience cognitive abnormalities in multiple domains including processing speed, executive function, and memory. Here we show that SLE patients carrying antibodies that bind DNA and the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), termed DNRAbs, displayed a selective impairment in spatial recall. Neural recordings in a mouse model of SLE, in which circulating DNRAbs penetrate the hippocampus, revealed that CA1 place c ...[more]

PMID: 26286205

Similar Datasets

Project description:PURPOSE OF REVIEW:Humoral autoimmunity has gained highest interest in neurology and psychiatry. Despite numerous recent articles on this hot topic, however, the biological significance of natural autoantibodies (AB) and the normal autoimmune repertoire of mammals remained quite obscure. AB may contribute to disorder-relevant phenotypes and are even believed to induce diseases themselves, but the circumstances under which AB become pathogenic are not fully understood. This review will focus on the highly frequent AB against the N-methyl-d-aspartate receptor 1 (NMDAR1-AB) as an illustrating example and provide a critical overview of current work (please note that the new nomenclature, GluN1, is disregarded here for consistency with the AB literature). In particular, it will demonstrate how little is known at this point and how many conclusions are drawn based on small numbers of individuals, fragmentary experimental approaches or missing controls. RECENT FINDINGS:NMDAR1-AB were investigated by clinicians world-wide with numerous small studies and case reports appearing yearly. Many publications were on 'anti-NMDAR encephalitis' cases or tried to separate those from other NMDAR1-AB associated conditions. Original exclusivity claims (e.g. electroencephalogram, EEG or functional magnetic resonance imaging, fMRI findings) turned out not to be exclusive for 'anti-NMDAR encephalitis'. Systematic analyses of representative NMDAR1-AB positive sera of all immunoglobulin (Ig) classes showed comparable distribution of different epitopes, often polyspecific/polyclonal, across health and disease. Sophisticated imaging tools provided findings on synapse trafficking changes induced by NMDAR1-AB from psychotic subjects but still lack epitope data to support any claimed disorder link. Persistently high titers of NMDAR1-AB (IgG) in immunized mice with open blood-brain barrier (BBB)-induced psychosis-like symptoms but failed to induce inflammation in the brain. Knowledge on peripheral NMDAR, for example in the immune system, and on potential inducers of NMDAR1-AB is only slowly increasing. SUMMARY:The present knowledge on the (patho) physiological role of NMDAR1-AB is very limited and still characterized by adamant rumors. Much more experimental work and more solid and informative clinical reports, including large numbers of subjects and adequate control groups, follow-up investigations and interdisciplinary approaches will be necessary to obtain a better understanding of the significance of humoral autoimmunity in general (in focus here: NMDAR1-AB) and its disease-relevance in particular.

Dataset Information

Selective Impairment of Spatial Cognition Caused by Autoantibodies to the N-Methyl-D-Aspartate Receptor.

Publications

Selective Impairment of Spatial Cognition Caused by Autoantibodies to the N-Methyl-D-Aspartate Receptor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets