000007489 001__ 7489
000007489 005__ 20240124114245.0
000007489 0247_ $$2DOI$$a10.6083/vh53ww25j
000007489 037__ $$aETD
000007489 245__ $$aInvestigation of N-methyl-D-aspartate receptor
000007489 260__ $$bOregon Health and Science University
000007489 269__ $$a2019
000007489 336__ $$aDissertation
000007489 502__ $$bPh.D.
000007489 520__ $$aAutoimmunity to membrane proteins in the central nervous system has been increasingly recognized as a cause of neuropsychiatric disease. A key recent development was the discovery of antibodies to NMDA receptors in some cases of encephalitis, characterized by cognitive changes, memory loss, seizures, and sometimes long-term morbidity or mortality. Treatment approaches and experimental studies have largely focused on the pathogenic role of these autoantibodies. Passive antibody transfer to mice has provided useful insights but does not produce the full spectrum of the human disease. Here we describe a unique de novo autoimmune mouse model of anti-NMDA receptor encephalitis. Active immunization of immune competent mice with conformationally-stabilized, native-like NMDA receptors induced a fulminant encephalitis with behavioral and pathologic characteristics similar to those observed in the human disorder. Our results provide evidence for neuroinflammation and immune cell infiltration as a component of the autoimmune response in mice. Use of transgenic mice indicated that mature T cells as well as antibody-producing cells were required for disease induction. Our results provide insights into disease pathogenesis as well as a platform for testing mechanisms of disease initiation and therapeutic approaches.
000007489 542__ $$fIn copyright - single owner
000007489 650__ $$aHippocampus$$020217
000007489 650__ $$aEncephalitis$$018375
000007489 650__ $$aAutoantibodies$$015233
000007489 650__ $$aAutoimmunity$$028491
000007489 6531_ $$aneuroinflammation
000007489 6531_ $$an-methyl-d-aspartate
000007489 6531_ $$areceptors
000007489 691__ $$aSchool of Medicine$$041369
000007489 692__ $$aVollum Institute$$041509
000007489 7001_ $$aJones, Brian E.
000007489 8564_ $$93b0b3f92-5a37-4e2a-aefc-4e052255600b$$s12401298$$uhttps://digitalcollections.ohsu.edu/record/7489/files/Jones.Brian.2019.pdf
000007489 905__ $$a/rest/prod/vh/53/ww/25/vh53ww25j
000007489 909CO $$ooai:digitalcollections.ohsu.edu:7489$$pstudent-work
000007489 980__ $$aTheses and Dissertations