Anti-
N-methyl-D-aspartate (
NMDA) receptor encephalitis manifests with precipitous
cognitive decline,
abnormal movements, and severe
seizures that can be challenging to control with conventional anti-seizure medications. We previously demonstrated that intracerebroventricular (i.c.v.) administration of cerebrospinal fluid from affected patients, or purified
NMDA receptor antibodies from
encephalitis patients to mice precipitated
seizures, thereby confirming that
antibodies are directly pathogenic for
seizures. Although different repertoires of anti-
NMDA receptor antibodies could contribute to the distinct clinical manifestations in
encephalitis patients, the role of specific
antibodies in the expression of
seizure, motor, and cognitive phenotypes remains unclear. Using three different patient-derived
monoclonal antibodies with distinct
epitopes within the N-terminal domain (NTD) of the
NMDA receptor, we characterized the seizure burden, motor activity and anxiety-related behavior in mice. We found that continuous administration of 5F5, 2G6 or 3C11
antibodies for 2 weeks precipitated
seizures, as measured with continuous EEG using cortical screw
electrodes. The seizure burden was comparable in all three antibody-treated groups. The
seizures were accompanied by increased hippocampal
C-C chemokine ligand 2 (CCL2)
mRNA expression 3 days after antibody infusion had stopped.
Antibodies did not affect the motor performance or anxiety scores in mice. These findings suggest that neuronal
antibodies targeting different
epitopes within the
NMDA receptor may result in a similar seizure phenotype.