Differential effect of dopamine deficiency on the expression of NMDA receptor subunits in the weaver mouse brain

The weaver mutant mouse is characterized by degeneration of the dopaminergic mesencephalic neurons. The role of the dopaminergic system in the regulation of N-methyl-d-aspartate (NMDA) receptor subunit expression was addressed in the present study. In situ hybridization experiments were conducted to determine the expression levels of the NMDA receptor subunit mRNAs, z1, epsilon1 and epsilon2, in striatum, nucleus accumbens, olfactory tubercle and cerebral cortical regions of 26-day-, 3- and 6-month-old weaver mice. Data indicated statistically significant increases in z1 and epsilon2 mRNA levels in 6-month-old weaver striatum, whereas at the same age epsilon1 mRNA expression was decreased in all striatal regions, as well as in the cortex. In the 26-day-old weaver striatum and nucleus accumbens, statistically significant increases were observed in epsilon1 mRNA levels, whereas no changes were observed in the other two subunits. In the somatosensory cortex of 26-day-old weaver brain an increased expression of all three subunits was observed. The upregulation of NMDA receptor subunit expression observed in the somatosensory cortex can be attributed to a decreased activity of the glutamatergic thalamocortical pathway, following the degeneration of the nigrostriatal dopaminergic fibres. In the striatum, the present results demonstrate a differential control on the expression of z1 and epsilon2 subunits on the one hand, and epsilon1 subunit on the other. It is suggested that dopamine exerts a negative control on the expression of z1 and epsilon2 subunits, through a downregulation of transcription factors associated with the AP1 regulatory site, which is mediated by the activation of striatal dopamine D2 receptors.