GABA_A receptor subunit expression in intrastriatal ventral mesencephalic transplants

Abstract.

To compare the expression of GABA_A receptor subunits in the normal substantia nigra and in fetal mesencephalic neurons ectopically transplanted into the dopamine-depleted striatum, we have employed single and double immunocytochemical approaches using tyrosine hydroxylase (TH) and α1, α2, α3, and β2/3 GABA_A receptor subunit specific antibodies. In the substantia nigra, α1 and β2/3 GABA_A receptor subunits were labeled in processes in the pars compacta (SNc) and, more intensely, in both somata and processes in the pars reticulata (SNr). There was no clear TH and α1 or β2/3 colocalization, with the exception of some TH-immunoreactive (-ir) neurons that showed a weak immunoreactivity for β2/3. Sections immunolabeled for α2 showed a faint diffuse labeling for this subunit both in the SNr and in the SNc. Scattered somata were immunopositive for α2, and some of them were also TH-ir. The labeling for α3 and TH showed that TH-positive neurons expressed intense α3 immunoreactivity, although some TH-negative somata in the SNr expressed weak α3 immunoreactivity. In the transplants, double immunostaining procedures showed that the labeling for α1 or β2/3 appeared particularly concentrated in patches of intensely immunoreactive neuronal processes that surrounded TH-ir cells, but these processes were not TH-ir. In the case of α2, diffuse immunostaining was observed all over the graft, with some scattered positive somata. Only a few of them were also TH positive. Sections immunoreacted for α3 and TH revealed that TH-ir neurons expressed intense α3 immunoreactivity, and that only a few TH-negative neurons were weakly positive for α3. These results show that mesencephalic tissue ectopically grafted into the striatum develops a pattern of GABA_A receptor expression similar to that normally expressed in situ, and particularly that the grafted dopaminergic neurons express similar GABA_A receptors, including the α3 subunit. This might be due to the similarity of GABAergic afferents to these neurons in the SNc and the graft, or that at the time of transplantation this expression had already been determined.