The involvement of <italic>N</italic>-methyl-d-aspartate receptor (NMDAR) subunit NR1 in the pathophysiology of schizophrenia

Abstract

Schizophrenia is a severe mental illness that afflicts nearly 1% of the world population. Although the exact pathophysiology of schizophrenia is unknown, the N-methyl-D-aspartate receptor (NMDAR), a major glutamate receptor subtype, has received great attention. The NR1 subunit is often considered indispensable for functional NMDAR assemblies, abnormal modulation of which is found in patients with schizophrenia. In this review, we discuss how disrupted function of NR1 subunits in NMDAR leads to the progression and development of symptoms of schizophrenia-like behaviors in a variety of genetically modified mouse models. We also discuss some of the susceptible genes and shared signaling pathways among the schizophrenia, and how their mutations lead to NR1 subunits hypofunction. Finally, we suggest that the subunit-selective modulators of NR1 subunits in NMDA receptors may be promising tools for the therapy of schizophrenia.

Anti-N-methyl-D-aspartate receptor(NMDAR) antibody encephalitis presents in atypical types and coexists with neuromyelitis optica spectrum disorder or neurosyphilis

“…Recent advances in genetic, preclinical and clinical pharmacological, and brain studies have shown the role of disrupted NMDAR-NR1 subunit-mediated glutamatergic pathways in schizophrenia [6]. Psychosis is a canonical symptom of anti-NMDAR encephalitis.…”

Comparative Pro-cognitive and Neurochemical Profiles of Glycine Modulatory Site Agonists and Glycine Reuptake Inhibitors in the Rat: Potential Relevance to Cognitive Dysfunction and Its Management

“…Glutamate activation of the NMDA receptor requires concurrent binding of glycine or, predominantly in the PFC, Dserine at the glycine modulatory site [6][7][8]. Thus, pharmacological modulation of the glycine site has been prioritised to restore hypofunction by direct agonism, inhibition of enzymes regulating serine metabolism or increasing synaptic glycine by inhibition of glycine transporters [9][10][11][12]. Although glycine and Dserine have been extensively characterised, it has proven very hard to generate small molecule, positive modulators of the glycine site.…”

Early life esophageal acid exposure reduces expression of NMDAR1 in the adult rat dorsal hippocampus and medial prefrontal cortex: Potential relationship with hyperlocomotion

“…30 NR1-knockdown rats also exhibited hyperlocomotion. 31 Based on these prior findings, we speculate that hyperlocomotion may be related to reduced NR1 expression in specific brain regions. Inhibitory synaptic transmission mediated by interneurons has a modulatory role in visceral pain.…”