Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB)

Luquin, Natasha, Sierra, Salvador, Rico, Alberto J, Gómez-Bautista, Virginia, Roda, Elvira, Conte-Perales, Lorena, Franco, Rafael, McCormick, Peter, Labandeira-García, José L and Lanciego, José L (2012) Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB). Neurobiology of Disease, 47 (3). pp. 347-57. ISSN 1095-953X

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Abstract

The A(2A)R has become a therapeutic target in Parkinson disease due to its functional role in the striatum, capable of modulating dopaminergic neurotransmission in the basal ganglia. No conclusive evidence, however, has been provided to demonstrate the existence of A(2A)Rs in the output nuclei of the basal ganglia: the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr). Using immunohistochemistry and in situ hybridization techniques we have confirmed the presence of A(2A)Rs in both the striatum (medium spiny and cholinergic neurons) and the external segment of the globus pallidus (GPe), in the monkey. The antibody routinely used to label A(2A)Rs failed to detect A(2A)R-positive neurons in the GPi and SNr, however, in situ hybridization showed that A(2A)R mRNA transcripts were indeed present in both these nuclei. Surprisingly, by labeling pallidothalamic and nigrothalamic projection neurons originating in the GPi and SNr with the neuronal retrograde tracer cholera toxin subunit B (CTB), the receptor protein was unmasked and detectable using the antibody. This unmasking of the protein was specific to CTB and not an artifact of the tracer. We have shown unequivocally that the A(2A)R is present in the output nuclei of the primate basal ganglia, however, to be able to detect the receptor immunohistochemically, unmasking the protein with CTB was necessary. The presence of A(2A)Rs in the GPi and SNr suggests that these output nuclei could be targeted therapeutically in Parkinson disease to restore abnormal activity in the basal ganglia.

Item Type: Article
Additional Information: Copyright © 2012 Elsevier Inc. All rights reserved.
Uncontrolled Keywords: animals,biotin,cholera toxin,choline o-acetyltransferase,corpus striatum,dextrans,glial fibrillary acidic protein,globus pallidus,macaca fascicularis,male,neural pathways,neurons,rna, messenger,receptors, adenosine a2
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 13 Jan 2014 13:10
Last Modified: 21 Apr 2020 22:45
URI: https://ueaeprints.uea.ac.uk/id/eprint/47149
DOI: 10.1016/j.nbd.2012.05.006

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