Gamma-Aminobutyric Acid A Receptor Subunit Expression and Cellular Localization in the Human Parkinsonian Globus Pallidus.

Abstract

The gamma-aminobutyric acid A (GABA_A) receptor is an important mediator of cellular signaling in the globus pallidus and might be implicated in the pathophysiology of Parkinson disease (PD). The goal of the present study was to characterize GABA_A receptor subunit expression in the normal and parkinsonian human globus pallidus. Postmortem brain specimens were obtained from 8 patients with pathological evidence of PD at autopsy and from 4 control patients without such evidence. These tissues were exposed to primary antibodies directed against the α1 and α3 subunits of the GABA_A receptor and were visualized and quantified using fluorescence microscopy. No differences were found in the pallidal neuronal density in the control versus PD tissues. Projection neurons strongly expressed the α1, α3, and β2 GABA_A receptor subunits. After normalizing the immunofluorescence intensities in the globus pallidus to those in the adjacent structures, no significant differences were found in GABA_A receptor subunit expression in the globus pallidus between the PD specimens and the control specimens. Compensatory changes in GABA_A receptor α1 and α3 subunit expression in response to PD-related signaling abnormalities in the globus pallidus did not occur in our PD cohort.