The schizophrenia-associated gene GRIN2A (glutamate ionotropic receptor NMDA type subunit 2a) codes for a protein subunit of the NMDA (N-methyl-D-aspartate) receptor that underlies central aspects of human cognition.
Published data suggest that GluN2A is involved in maturation and phenotypic maintenance of parvalbumin interneurons (PVIs), and these interneurons suffer from a deficient glutamatergic neurotransmission via GluN2A-containing NMDARs in schizophrenia.
GluN2A subunit containing N-methyl-d-aspartate receptors (NMDARs) are highly involved in various physiological processes in the central nervous system, but also in some diseases, such as anxiety, depression and schizophrenia.
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.
Comparisons between control and schizophrenia groups reveal that GluN2A, GAD67 and DRD2 are differentially regulated between diagnostic groups in a genotype specific manner.
This proposal links an established risk gene with a psychological process central to psychosis and is supported by findings of comparable deficits in short-term habituation in mice lacking the NMDAR receptor subunit Grin2a (which also shows association to schizophrenia).
The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation in the offspring interacted with maternal herpes simplex virus-2 (HSV-2) seropositivity during pregnancy influencing the risk of schizophrenia later in life.
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.
The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation in the offspring interacted with maternal herpes simplex virus-2 (HSV-2) seropositivity during pregnancy influencing the risk of schizophrenia later in life.
These findings suggest that glutamatergic neurotransmission via NR2A-containing NMDA receptors on PV neurons in the PFC may be deficient in schizophrenia.
In order to investigate whether early VH lesion in rats alters the expression of genes implicated in schizophrenia pre- and post-puberty, we studied the mRNA expression of neuropeptides (substance P, dynorphin and enkephalin), dopamine D1, dopamine D2, and NMDA (subunits NR1 and NR2A) receptors in this animal model.
These observations suggest that, in schizophrenia, a number of CB-containing cells that normally do not express NR2A might become NR2A-expressing or, perhaps not mutually exclusively, the number of CB-expressing cells might be increased and these cells express NR2A.
In addition, the density of the GAD67+/NR2A+ neurons was decreased by 57% and 49% in layers 3 and 4, respectively, in schizophrenia, but it was unchanged in bipolar disorder.
However, compared with the normal control subjects and subjects with bipolar disorder, the density of CB+/NR2A+ neurons in layer 2 was increased by 41% to 44 % in subjects with schizophrenia, whereas the amount of NR2A mRNA/CB+ neurons was unchanged.
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.
The glutamatergic hypothesis of schizophrenia lead recently to a first successful mGlu2/3 receptor agonistic drug and is underpinned by significant findings in genes regulating the glutamatergic system (SLC1A6, SLC1A2 GRIN1, GRIN2A, GRIA1, NRG1, ErbB4, DTNBP1, DAAO, G72/30, GRM3).
In the present study, we performed western blot analysis to determine whether protein levels of NMDA receptor subunits (NR1, NR2A, NR2B) and associated PSD proteins (NF-L, PSD95, SAP102) are altered in schizophrenia.
Our results indicate that the (GT)n polymorphism in the promoter of GRIN2A gene may play a significant role in the etiology of schizophrenia among our samples.