Recent data have suggested an involvement of the N-methyl-D-aspartate receptor (NMDA-R) signalling complex in schizophrenia pathophysiology. Ubiquitously expressed NR1 subunit, existing in 8 spliced variants, is required for the formation of functional NMDA-Rs. Regional, gender and age-dependent differences in the expression of mRNA and protein of NR1 subunit have been observed. As the expression of C-terminal NR1 isoforms is associated with different pathways for synaptic NMDA-R trafficking and targeting, we have measured levels of mRNA (quantitative RT-PCR) and protein of NR1 and splice isoform NR1C2 (western blot) in post-mortem left and right hippocampi of elderly patients with schizophrenia and non-psychiatric controls. In contrast to previous findings, we did not detect significant differences in the mRNA levels for panNR1 subunit between schizophrenia and control group. However, we found significant changes in the absolute values of the transcripts associated with schizophrenia, but independent on sex. The expression of panNR1 and NR1C2 proteins exhibited sex difference. Higher protein levels were found in the left hippocampi of women (both schizophrenia and controls) whereas in men the levels were higher in the right hippocampus. Also the interactions of laterality and gender were statistically significant. Further comparison revealed significant sex-dependent laterality comparing schizophrenia and control groups. The significance disappeared in women subgroups. The results suggest that hippocampal differences in the expression of mRNA and protein for pan-form and NR1C2 variant of the NMDA-R1 subunit exhibit significant sex-dependence having in mind that the data are limited in the number of patients/controls.

Supported by IGAMZCR8792