NMDARs , N-methyl-D-aspartate receptors, composed of GluN1 and GluN3 are only activated by glycine (a neurotransmitter that mediates signaling when bonded to pentameric glycine receptors). GluN1-3 NMDARs are most essential for the regulation of neuronal excitability, behavior, and circuit function. This article conducted a structural analysis that revealed  unique features of GluN1a-3A NMDARs (compared to GluN1-2B NMDAR).The authors hypothesized that the differing subunit arrangement of the GluN1a-3A NMDAR (that was bound to glycine) may show a “desensitized state”.

University of Illinois at Chicago

Examinations of hundreds of cases shows that some patients show only psychiatric symptoms without neurological action during relapse or the first disease episode. The following figure shows NMDA receptor antibodies during relapse and the first phase in a single patient. NMDAR titers (antibody level) were higher in relapse than the initial phase. These patients are no different to others with the disease in terms of presence/absence of tumor, demographics, psychiatric symptoms or outcomes of those with anti-NMDA encephalitis. Furthermore, those patients with antibodies (IgG subtype) reacting to the GluN1 subunit display psychiatric symptoms in solitarity. 

Anti-NMDAR Antibodies and psychosis 

Michalski, K., & Furukawa, H. (2024, April 12). Structure and function of GLUN1-3A NMDA receptor excitatory glycine receptor channel. Science advances. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006217/#:~:text=The%20GluN1%2D3%20NMDARs%20are,molecular%20level%20has%20remained%20limited. 

GLUN1-3A Receptor function and structure

Anti-NMDAR encephalitis and psychotic symptoms are caused by IgG antibodies that recognize the GluN1 subunit. An examination of occurring symptoms from patients with early psychosis (who also later met criteria for schizophrenia-like illnesses) unveiled no presence of IgG GluN1 antibodies in patients/controls. These findings align with a previous study where patients failed to show GluN1 IgG auto-antibodies with schizophrenia. 

Learn Before

Related