NMDAR Antibodies Alter Dopamine Receptors and Cause Psychotic Behavior in Mice.
Adolescent
Adult
Animals
Anti-N-Methyl-D-Aspartate Receptor Encephalitis
/ cerebrospinal fluid
Autoantibodies
/ cerebrospinal fluid
Female
Humans
Male
Mice
Mice, Inbred C57BL
Neurons
/ drug effects
Psychotic Disorders
Rats
Rats, Wistar
Receptors, Dopamine
/ drug effects
Reflex, Startle
/ drug effects
Young Adult
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
05
04
2020
revised:
17
06
2020
accepted:
21
06
2020
pubmed:
26
6
2020
medline:
5
1
2021
entrez:
26
6
2020
Statut:
ppublish
Résumé
The aim was to demonstrate that antibodies from patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis alter the levels of dopamine 1 receptor (D1R) and dopamine 2 receptor (D2R) and cause psychotic-like features in mice. Cultured rat hippocampal neurons were treated with cerebrospinal fluid (CSF) from patients with anti-NMDAR encephalitis or controls, and the effects on clusters of D1R and D2R were quantified. In vivo studies included 71 C57BL/6J mice that were chronically infused with CSF from patients or controls through ventricular catheters connected to subcutaneous osmotic pumps. Prepulse inhibition of the acoustic startling reflex (PPI; a marker of psychotic-like behavior), memory, locomotor activity, and the density of cell-surface and synaptic D1R, D2R, and NMDAR clusters were examined at different time points using reported techniques. In cultured neurons, CSF from patients, but not from controls, caused a significant decrease of cell-surface D1R and an increase of D2R clusters. In mice, CSF from patients caused a significant decrease of synaptic and total cell-surface D1R clusters and an increase of D2R clusters associated with a decrease of PPI. These effects were accompanied by memory impairment and a reduction of surface NMDARs, as reported in this model. The psychotic-like features, memory impairment, and changes in levels of D1R, D2R, and NMDAR progressively improved several days after the infusion of CSF from patients stopped. In addition to memory deficits and reduction of NMDARs, CSF antibodies from patients with anti-NMDAR encephalitis cause reversible psychotic-like features accompanied by changes (D1R decrease, D2R increase) in cell-surface dopamine receptor clusters. ANN NEUROL 2020 ANN NEUROL 2020;88:603-613.
Substances chimiques
Autoantibodies
0
Receptors, Dopamine
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
603-613Informations de copyright
© 2020 American Neurological Association.
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