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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2010

Open Access 01-12-2010 | Research

In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction

Authors: Mario Manto, Josep Dalmau, Adrien Didelot, Véronique Rogemond, Jérôme Honnorat

Published in: Orphanet Journal of Rare Diseases | Issue 1/2010

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Abstract

Background

A severe encephalitis that associates with auto-antibodies to the NR1 subunit of the NMDA receptor (NMDA-R) was recently reported. Patients' antibodies cause a decrease of the density of NMDA-R and synaptic mediated currents, but the in vivo effects on the extracellular glutamate and glutamatergic transmission are unknown.

Methods

We investigated the acute metabolic effects of patients' CSF and purified IgG injected in vivo. Injections were performed in CA1 area of Ammon's horn and in premotor cortex in rats.

Results

Patient's CSF increased the concentrations of glutamate in the extracellular space. The increase was dose-dependent and was dramatic with purified IgG. Patients' CSF impaired both the NMDA- and the AMPA-mediated synaptic regulation of glutamate, and did not affect the glial transport of glutamate. Blockade of GABA-A receptors was associated with a marked elevation of extra-cellular levels of glutamate following a pretreatment with patients' CSF.

Conclusion

These results support a direct role of NMDA-R antibodies upon altering glutamatergic transmission. Furthermore, we provide additional evidence in vivo that NMDA-R antibodies deregulate the glutamatergic pathways and that the encephalitis associated with these antibodies is an auto-immune synaptic disorder.
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Metadata
Title
In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction
Authors
Mario Manto
Josep Dalmau
Adrien Didelot
Véronique Rogemond
Jérôme Honnorat
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2010
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-5-31

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