Human NMDAR autoantibodies disrupt excitatory-inhibitory balance, leading to hippocampal network hypersynchrony.
CP: Neuroscience
NMDA receptor
NMDA receptor encephalitis
autoantibodies
excitatory-inhibitory imbalance
microglia
network oscillation
neural network modeling
θ-γ coupling
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
31 10 2023
31 10 2023
Historique:
received:
31
05
2022
revised:
30
06
2023
accepted:
07
09
2023
medline:
6
11
2023
pubmed:
28
9
2023
entrez:
28
9
2023
Statut:
ppublish
Résumé
Anti-NMDA receptor autoantibodies (NMDAR-Abs) in patients with NMDAR encephalitis cause severe disease symptoms resembling psychosis and cause cognitive dysfunction. After passive transfer of patients' cerebrospinal fluid or human monoclonal anti-GluN1-autoantibodies in mice, we find a disrupted excitatory-inhibitory balance resulting from CA1 neuronal hypoexcitability, reduced AMPA receptor (AMPAR) signaling, and faster synaptic inhibition in acute hippocampal slices. Functional alterations are also reflected in widespread remodeling of the hippocampal proteome, including changes in glutamatergic and GABAergic neurotransmission. NMDAR-Abs amplify network γ oscillations and disrupt θ-γ coupling. A data-informed network model reveals that lower AMPAR strength and faster GABA
Identifiants
pubmed: 37768823
pii: S2211-1247(23)01178-6
doi: 10.1016/j.celrep.2023.113166
pii:
doi:
Substances chimiques
Receptors, N-Methyl-D-Aspartate
0
Autoantibodies
0
Receptors, AMPA
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113166Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests J.D. receives royalties from Euroimmun for the use of the NMDA receptor as an antibody test.