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

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

  • J Neuroinflammation. 2021 Feb 21;18(1):53. doi: 10.1186/s12974-021-02107-0.
Yuewen Ding 1 2,  Zheye Zhou 3,  Jinyu Chen 1,  Yu Peng 1,  Haitao Wang 4,  Wei Qiu 5,  Wei Xie 6,  Jun Zhang 7,  Honghao Wang 8
Affiliations

Affiliations

  • 1 Department of Neurology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, Guangdong, 510515, People's Republic of China.
  • 2 School of Traditional Chinese Medicine, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, Guangdong, People's Republic of China.
  • 3 School of Biomedical Engineering, Liuzhou Traditional Chinese Medicine Hospital, Guangzhou, Guangdong, People's Republic of China.
  • 4 School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
  • 5 Department of Neurology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
  • 6 School of Traditional Chinese Medicine, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, Guangdong, People's Republic of China. [email protected].
  • 7 Department of Internal Medicine, Division of Nephrology, University of California at Davis, Houston, TX, USA. [email protected].
  • 8 Department of Neurology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, Guangdong, 510515, People's Republic of China. [email protected].
PMID: 33612107 DOI: 10.1186/s12974-021-02107-0
Abstract

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 (GluN1356-385).

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 GluN1356-385 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.

Keywords

Active immunization; Amino-terminal domain; Anti-NMDA receptor encephalitis; Cerebrospinal fluid; GluN1.

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