Changes in the gene expression of GABA(A) receptor alpha(1) and alpha(2) subunits and metabotropic glutamate receptor 5 in the basal ganglia of the rats with unilateral 6-hydroxydopamine lesion and embryonic mesencephalic grafts

By using an animal model of parkinsonism, we examined the expression of GAB A(A) receptor (R) and metabotropic glutamate receptor (mGluR) 5 in the basa l ganglia after transplantation with dopamine-rich tissue. The adult rats w ere unilaterally lesioned by the injection of 6-hydroxydopamine to their le ft medial forebrain bundles. At 5-10 weeks following the dopaminergic dener vation, the levels of GABA,R in the left caudate-putamen and globus pallidu s were about 20 and 16% lower than that of the right intact (control) sides , as shown by [H-3]flunitrazepam binding autoradiography on the brain secti ons. However, the receptor density increased to around 132 and 130% of cont rol levels in the entopeduncular nucleus and substantia nigra pars reticula ta of the lesioned sides. Furthermore, in situ hybridization analysis exhib ited parallel trends of changes in the levels of the GABA(A)R alpha (1), an d alpha (2) subunit and mGluR5 mRNAs in the neurons of the brain regions wi th that of the proteins detected by the binding assay. A number of the rats 5 weeks postlesion were transplanted with the ventral mesencephalon of the embryonic rat into their left striata, Five weeks later, the changes in th e [SH]flunitrazepam binding seemed to be recovered by approximately 50-63% on the grafted sides of the areas. Moreover, the transplantation appeared t o produce a nearly complete reversal of the lesion-induced alterations in t he levels of the mRNAs. Thus, the data indicate the mechanism of gene regul ation for the modified expression of the receptors and could implicate the participation of the receptors in the pathogenesis of Parkinson's disease. (C) 2001 Academic Press.