Epileptogenic effects of NMDAR antibodies in a passive transfer mouse model

Objective: Glutamate is an excitatory neurotransmitter in the brain and acts via the NMDA receptor (NMDAR; N-methyl D-aspartate receptor). Like other receptors, the NMDAR is made up of various submits. One cause of inflammation in the brain (or, encephalitis) is an autoimmune reaction to a NMDAR subunit. This condition, known as "NMDA receptor antibody encephalitis" is associated with psychosis, agitation and violent behavior which may be followed by seizures. A recent book recounts the experience of a young journalist with this condition. How the NMDAR antibody causes seizures is not fully known; hence, in this study, the authors injected the human antibody directly into the brains of experimental mice. The antibody was injected by itself and then with a drug that produces seizures (i.e. a chemoconvulsant- in this case, pentylenetetrazol or PTZ).

Results: Mice injected with the antibody did not show spontaneous seizures. However, they were more susceptible to seizures caused by PTZ as compared to those given the sham (inactive) antibody. The antibody bound preferentially to the hippocampus – a part of the brain important for seizures, and the level of antibody bound to NMDARs correlated with the seizures that the mice experienced.

Interpretation: This study showed that the antibody against NMDARs injected directly into the brain can worsen seizures caused by PTZ. This study forms one of the first studies to understand the seizure-inducing capacity of the NMDAR antibody.

Summary for specialists