GluN1(359-378) is a peptide fragment associated with the N-methyl-D-aspartate receptor (NMDAR). GluN1(359-378) can cross the blood-brain barrier and mimic a specific antigenic epitope on the NMDAR, triggering an autoimmune response that leads to the internalization or degradation of NMDARs on the neuronal surface, thereby affecting neurotransmission. GluN1(359-378) is primarily used in research related to anti-NMDAR encephalitis[1].
In vivo, in a mouse model of anti-NMDAR encephalitis, C57BL/6 mice were actively immunized by subcutaneous injection of 200μg of the GluN1(359-378) peptide antigen emulsified in Complete Freund's Adjuvant. The emulsion was administered at four sites (shoulder and flank regions) with 50μL per site on day 0, and pertussis toxin was injected intraperitoneally on days 0 and 2. GluN1(359-378) induced a specific, polyfunctional (Th1/Th17/Tfh) CD4⁺ and CD8⁺ T-cell response targeting the GluN1 subunit. GluN1(359-378) drove the production of pathogenic anti-GluN1 antibodies through T-B cell collaboration, activated B cells, and up-regulated the expression of proteins associated with cytokine signaling pathways[2]. C57BL/6 mice were actively immunized by subcutaneous injection of 200μL of the GluN1(359-378) peptide antigen emulsion on day 0, followed by intraperitoneal injection of pertussis toxin on days 0 and 2, over an immunization period of 14 days. GluN1(359-378) increased seizure susceptibility in mice. GluN1(359-378) disrupted the NMDAR-EphB2 interaction, leading to reduced GluN1 expression on the neuronal postsynaptic membrane, down-regulation of EphB2/EphrinB2 proteins, alterations in synaptic ultrastructure, and a decrease in dendritic spine density[3].
References:
[1] Huang H, Huang Y, Li S, et al. Elevated Release of Presynaptic Glutamate: The Potential Pathogenesis of Anti-NMDAR Encephalitis-Associated Seizures. CNS Neurosci Ther. 2025 Oct;31(10):e70585.
[2] Lesec L, Serrier J, Seillier C, et al. Specific and Polyfunctional T Cell Response Against N-Methyl-d-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model. Biomedicines. 2024 Oct 25;12(11):2458.
[3] Qian K, Meng Y, Zhang L, et al. Effects and Mechanisms of NMDAR-EphB2 on Synapses in Mice by Active Immunization with a GluN1 Peptide. Mol Neurobiol. 2025 Dec;62(12):15988-16000.