A juvenile mouse model of anti-N-methyl-D-aspartate receptor encephalitis by active immunization
Shuyu He1,2,3, Chongyang Sun1,4, Qian Zhu1,2
1Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institution, Shenzhen, China.
Introduction:
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a common autoimmune encephalitis, and it is associated with psychosis, dyskinesia, and seizures. Anti-NMDAR encephalitis (NMDARE) in juveniles and adults presents different clinical charactreistics. However, the pathogenesis of juvenile anti-NMDAR encephalitis remains unclear, partly because of a lack of suitable animal models.
Methods:
We developed a model of juvenile anti-NMDAR encephalitis using active immunization with an amino terminal domain peptide from the GluN1 subunit (GluN1356 - 385) against NMDARs in 3-week-old female C57BL/6J mice.
Results:
Immunofluorescence staining suggested that autoantibody levels in the hippocampus increased, and HEK-293T cells staining identified the target of the autoantibodies as GluN1, suggesting that GluN1-specific immunoglobulin G was successfully induced. Behavior assessment showed that the mice suffered significant cognition impairment and sociability reduction, which is similar to what is observed in patients affected by anti-NMDAR encephalitis. The mice also exhibited impaired long-term potentiation in hippocampal CA1. Pilocarpine-induced epilepsy was more severe and had a longer duration, while no spontaneous seizures were observed.
Conclusion:
The juvenile mouse model for anti-NMDAR encephalitis is of great importance to investigate the pathological mechanism and therapeutic strategies for the disease, and could accelerate the study of autoimmune encephalitis.
Insights
Researchers developed a novel mouse model for juvenile anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. This model mimics key cognitive and behavioral deficits seen in human patients, aiding research into autoimmune encephalitis.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a significant autoimmune disorder.
- Juvenile and adult forms of anti-NMDAR encephalitis exhibit distinct clinical features.
- The pathogenesis of juvenile anti-NMDAR encephalitis is poorly understood due to a lack of appropriate animal models.
Purpose of the Study:
- To establish a juvenile mouse model for anti-NMDAR encephalitis.
- To investigate the pathological mechanisms and potential therapeutic strategies for juvenile anti-NMDAR encephalitis.
Main Methods:
- Active immunization of 3-week-old female C57BL/6J mice with a GluN1 subunit peptide (GluN1356 - 385).
- Assessment of autoantibody induction, behavioral changes, cognitive impairment, and hippocampal long-term potentiation.
- Evaluation of seizure susceptibility using pilocarpine induction.
Main Results:
- Successful induction of GluN1-specific immunoglobulin G autoantibodies.
- Significant cognitive impairment and reduced sociability in the modeled mice.
- Impaired hippocampal long-term potentiation and exacerbated pilocarpine-induced epilepsy.
Conclusions:
- The developed juvenile mouse model accurately reflects key aspects of human anti-NMDAR encephalitis.
- This model is crucial for advancing the understanding of autoimmune encephalitis pathogenesis.
- The model will accelerate research into novel therapeutic strategies for anti-NMDAR encephalitis.
