Anti-NMDAR encephalitis induced in mice by active immunization with a peptide from the amino-terminal domain of the GluN1 subunit

Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesia, and seizures. However, the underlying mechanisms of this disease remain unclear, in part because of a lack of suitable animal models. Methods This study describes a novel female C57BL/6 mouse model of anti-NMDAR encephalitis that was induced by active immunization against NMDARs using an amino terminal domain (ATD) peptide from the GluN1 subunit (GluN1(356-385)). Results Twelve weeks after immunization, the immunized mice showed significant memory loss. Furthermore, antibodies from the cerebrospinal fluid of immunized mice decreased the surface NMDAR cluster density in hippocampal neurons which was similar to the effect induced by the anti-NMDAR encephalitis patients' antibodies. Immunization also impaired long-term potentiation at Schaffer collateral-CA1 synapses and reduced NMDAR-induced calcium influx. Conclusion We established a novel anti-NMDAR encephalitis model using active immunization with peptide GluN1(356-385) targeting the ATD of GluN1. This novel model may allow further research into the pathogenesis of anti-NMDAR encephalitis and aid in the development of new therapies for this disease.

Automated summary

The study established a novel mouse model of anti-NMDAR encephalitis by actively immunizing against NMDARs with a peptide targeting the ATD of GluN1. Immunized mice showed significant memory loss and decreased surface NMDAR cluster density in hippocampal neurons, similar to effects observed in patients with anti-NMDAR encephalitis. These findings may contribute to further research on the pathogenesis of anti-NMDAR encephalitis and the development of new therapies for this disease.