Autoimmune receptor encephalitis in ApoE(‑/‑) mice induced by active immunization with NMDA1

Subacute progressive neuropsychiatric symptoms with cognitive and motor impairment and autoimmune seizures are some of the typical symptoms of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. The mechanisms underlying this disease are yet to be elucidated, which could be partly attributed to the lack of appropriate animal models. The present study aimed to establish an active immune mouse model of anti-NMDAR encephalitis. Mice were immunized with the extracellular segment of the NMDA1 protein, then subjected to open-field and novel object recognition experiments. Plasma was collected after euthanasia on day 30 after immunization and anti-NMDA1 antibodies were detected using ELISA. Furthermore, brain slices were analyzed to measure postsynaptic density protein 95 (PSD-95) and NMDA1 expression. Western blot analysis of NMDA1 and PSD-95 protein expression levels in the hippocampus was also performed. In addition, protein expression levels of PSD-95 and NMDA1 in mouse neuronal HT-22 cells were evaluated. Compared with controls, mice immunized with NMDA1 exhibited anxiety, depression and memory impairment. Moreover, high anti-NMDA1 antibody titers were detected with ELISA and the levels of anti-NMDA1 antibody reduced postsynaptic NMDA1 protein density in the mouse hippocampus. These findings demonstrated the successful construction of a novel mouse model of anti-NMDAR encephalitis by actively immunizing the mice with the extracellular segment of the NMDA1 protein. This model may be useful for studying the pathogenesis and drug treatment of anti-NMDAR encephalitis in the future.