Changes in the gene expression of GABAA receptor α1 and α2 subunits and metabotropic glutamate receptor 5 in the basal ganglia of the rats with unilateral 6-hydroxydopamine lesion and embryonic mesencephalic grafts
Journal
Experimental Neurology
Journal Volume
168
Journal Issue
2
Pages
231-241
Date Issued
2001
Author(s)
Abstract
By using an animal model of parkinsonism, we examined the expression of GABA(A) receptor (R) and metabotropic glutamate receptor (mGluR) 5 in the basal ganglia after transplantation with dopamine-rich tissue. The adult rats were unilaterally lesioned by the injection of 6-hydroxydopamine to their left medial forebrain bundles. At 5-10 weeks following the dopaminergic denervation, the levels of GABA(A)R in the left caudate-putamen and globus pallidus were about 20 and 16% lower than that of the right intact (control) sides, as shown by [3H]flunitrazepam binding autoradiography on the brain sections. However, the receptor density increased to around 132 and 130% of control levels in the entopeduncular nucleus and substantia nigra pars reticulata of the lesioned sides. Furthermore, in situ hybridization analysis exhibited parallel trends of changes in the levels of the GABA(A)R alpha1 and alpha2 subunit and mGluR5 mRNAs in the neurons of the brain regions with 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 the [3H]flunitrazepam binding seemed to be recovered by approximately 50-63% on the grafted sides of the areas. Moreover, the transplantation appeared to produce a nearly complete reversal of the lesion-induced alterations in the levels of the mRNAs. Thus, the data indicate the mechanism of gene regulation for the modified expression of the receptors and could implicate the participation of the receptors in the pathogenesis of Parkinson's disease.
SDGs
Publisher
Academic Press Inc.
Type
journal article