Publication details
Expression of hippocampal NMDA receptor GluN1 subunit and its splicing isoforms in schizophrenia: postmortem study
| Authors | |
|---|---|
| Year of publication | 2010 |
| Type | Article in Periodical |
| Magazine / Source | Neurochemical Research |
| MU Faculty or unit | |
| Citation | |
| Field | Psychiatry, sexuology |
| Keywords | Schizophrenia; Hippocampus; GluN1 subunit of NMDA receptor; splice variants; laterality |
| Description | There is accumulating evidence that disturbances in the N-methyl-D-aspartate receptor (NMDA-R) functioning are associated with the pathogenesis of schizophrenia. To assess actual changes in the expression of the GluN1 subunit and its isoforms, we measured absolute differences in the levels of mRNA/protein for panGluN1 (8 isoforms altogether) as well as the mRNA individual isoforms in the post-mortem left/right hippocampus of patients with schizophrenia in comparison with non-psychiatric subjects. There were no significant differences in the panGluN1subunit mRNA expression, but the absolute left-right differences were much more pronounced in the patients with schizophrenia. Protein levels of the GluN1 subunit in the left hippocampus in male schizophrenic patients were lower in comparison with controls. The expression of the NR1-4b isoform was attenuated in the left whereas the NR1-2b was reduced in the right hippocampus of schizophrenic patients. Isoforms associated with the efficiency of NMDA induced gene expression and with phosphorylation occurred more commonly in schizophrenic hippocampi. Together, our study suggests that NMDA-R hypofunction in schizophrenia may be selectively dependent on the dysregulation of GluN1 subunit expression, which exhibits a somewhat different expression in the left/right hippocampus of psychotic patients. |