N-Methyl-D-Aspartate Receptor Antibodies in Autoimmune Encephalopathy Alter Oligodendrocyte Function.
Adolescent
Adult
Animals
Anti-N-Methyl-D-Aspartate Receptor Encephalitis
/ immunology
Autoantibodies
/ cerebrospinal fluid
Autoantigens
/ immunology
Cells, Cultured
Child
Female
Glucose Transporter Type 1
/ biosynthesis
Humans
Male
Oligodendroglia
/ drug effects
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate
/ immunology
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:
05 2020
05 2020
Historique:
received:
09
04
2019
revised:
15
01
2020
accepted:
06
02
2020
pubmed:
14
2
2020
medline:
24
7
2020
entrez:
14
2
2020
Statut:
ppublish
Résumé
Antibodies against neuronal N-methyl-D-aspartate receptors (NMDARs) in patients with anti-NMDAR encephalitis alter neuronal synaptic function and plasticity, but the effects on other cells of the nervous system are unknown. Cerebrospinal fluid (CSF) of patients with anti-NMDAR encephalitis (preabsorbed or not with GluN1) and a human NMDAR-specific monoclonal antibody (SSM5) derived from plasma cells of a patient, along the corresponding controls, were used in the studies. To evaluate the activity of oligodendrocyte NMDARs and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in vitro after exposure to patients' CSF antibodies or SSM5, we used a functional assay based on cytosolic Ca NMDAR agonist responses were robustly reduced after preincubation of oligodendrocytes with patients' CSF or SSM5 but remained largely unaltered with the corresponding controls. These effects were NMDAR specific, as patients' CSF did not alter responses to AMPA receptor agonists and was abrogated by preabsorption of CSF with HEK cells expressing GluN1 subunit. Patients' CSF also reduced oligodendrocyte expression of glucose transporter GLUT1 induced by NMDAR activity. Antibodies from patients with anti-NMDAR encephalitis specifically alter the function of NMDARs in oligodendrocytes, causing a decrease of expression of GLUT1. Considering that normal GLUT1 expression in oligodendrocytes and myelin is needed to metabolically support axonal function, the findings suggest a link between antibody-mediated dysfunction of NMDARs in oligodendrocytes and the white matter alterations reported in patients with this disorder. ANN NEUROL 2020;87:670-676.
Substances chimiques
Autoantibodies
0
Autoantigens
0
Glucose Transporter Type 1
0
Receptors, N-Methyl-D-Aspartate
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
670-676Informations de copyright
© 2020 American Neurological Association.
Références
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