Using mature miRNA profiling and quantitative real-time PCR (qRT-PCR) in the orbitofrontal cortex (OFC) of SCZ (N = 29; 20 male and 9 female), BD (N = 26; 12 male and 14 female), and unaffected control (N = 25; 21 male and 4 female) subjects, we uncovered that miR-223, an exosome-secreted miRNA that targets glutamate receptors, was increased at the mature miRNA level in the OFC of SCZ and BD patients with positive history of psychosis at the time of death and was inversely associated with deficits in the expression of its targets glutamate ionotropic receptor NMDA-type subunit 2B (GRIN2B) and glutamate ionotropic receptor AMPA-type subunit 2 (GRIA2).
In a recent weighted burden analysis of exome-sequenced schizophrenia cases and controls, we noted modest statistical evidence for an enrichment of rare, functional variants in FYN, GRIN1, and GRIN2B in schizophrenia cases.
Changes in GRIN2B promoter methylation may represent an environmental influence contributing to glutamatergic dysfunction in psychosis and relate to lower cognitive performance in subjects with first-episode schizophrenia.
We analyzed several variants located in the GluN2B C terminus and found that three variants in patients with autism (S1415L) or schizophrenia (L1424F and S1452F) (S1413L, L1422F, and S1450F in rodents, respectively) displayed impaired binding to membrane-associated guanylate kinase (MAGUK) proteins.
Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC.
The selective loss of NR2B protein and subsequent synaptic dysfunction weakens plPFC function during development and may underlie early cognitive impairments in SCZ models and patients.
The selective loss of NR2B protein and subsequent synaptic dysfunction weakens plPFC function during development and may underlie early cognitive impairments in SCZ models and patients.
GRIN2B variants were genotyped using standard TaqMan procedures in 175 European patients with schizophrenia deemed resistant or intolerant to treatment.
A surprising number of variants have been found in the N-methyl-d-aspartate receptor (NMDAR) gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental delay, epilepsy, and schizophrenia.
In this study, we performed a case-control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population.
These findings suggest that GRIN2B may be associated with schizophrenia and interaction effects of the polymorphisms in hsa-miR-219, CAKM2G, GRIN2B and GRIN3A may confer susceptibility to schizophrenia in the Chinese Han population.
Genetic variation in the NR2B gene predicts reduced levels of the obligatory NR1 subunit, suggesting a novel mechanism by which the NR2B SNP may negatively influence other NMDAR subunit expression and reasoning ability in schizophrenia.
These results suggest that SLC1A1, GRIN2B, and interactions between the two may potentially confer a susceptibility to OC symptoms in schizophrenia patients receiving clozapine.
The significant associations and interactions were located at the 3' region of GRIN2B suggesting that genetic variation in this part of the gene may be involved in the pathophysiology of schizophrenia.
Variations in the N-methyl-d-aspartate receptor 2B subunit gene (GRIN2B) have been associated with schizophrenia, a psychiatric disorder associated with reduced left-hemispheric language dominance.
The present results support the hypothesis that rare de novo mutations in GRIN2A or GRIN2B can be associated with cases of sporadic SCZ or ASD, just as it has recently been described for the related neurodevelopmental disease intellectual disability.
We found decreased NR1 expression in all three illnesses, decreased NR2A in schizophrenia and major depression, and decreased NR2C in schizophrenia.We found no changes of NR2B or NR2D.