Anti-NMDA receptor encephalitis in mice induced by active immunization with conformationally-stabilized holoreceptors

BioRxiv : the Preprint Server for Biology
Brian E JonesGary L Westbrook

Abstract

Autoimmunity to membrane proteins in the central nervous system has been increasingly recognized as a cause of neuropsychiatric disease. A key recent development was the discovery of antibodies to NMDA receptors in limbic encephalitis, characterized by cognitive changes, memory loss, seizures and sometimes long-term morbidity or mortality. Treatment approaches and experimental studies have largely focused on the pathogenic role of these autoantibodies. Passive antibody transfer to mice has provided useful insights, but does not produce the full spectrum of the human disease. Here we describe a de novo autoimmune mouse model of anti-NMDA receptor encephalitis. Active immunization of immune competent mice with conformationally-stabilized, native-like NMDA receptors induced a fulminant encephalitis that was strikingly similar to the behavioral and pathologic characteristics of human cases. Our results provide evidence of neuroinflammation and immune cell infiltration as early and robust features of the autoimmune response. Use of transgenic mice indicated that mature T cells as well as antibody-producing cells were required for disease induction. Our results provide new insights into disease pathogenesis as well as a platform for ...Continue Reading

Related Concepts

Amnesia
Autoantibodies
Autoimmune Diseases
Autoimmune Response
Encephalitis
Induction, Genetic
Immunization
Inflammation
Membrane Proteins
Laboratory mice

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis is a form of of brain inflammation due to antibodies against NMDA receptors. Discover the latest research on anti-NMDA receptor encephalitis here.

© 2021 Meta ULC. All rights reserved