Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB)
The A2AR 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 A2ARs in the output nuclei of the ba...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-09-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996112001921 |
| _version_ | 1818337259128094720 |
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| author | Natasha Luquin Salvador Sierra Alberto J. Rico Virginia Gómez-Bautista Elvira Roda Lorena Conte-Perales Rafael Franco Peter McCormick José L. Labandeira-García José L. Lanciego |
| author_facet | Natasha Luquin Salvador Sierra Alberto J. Rico Virginia Gómez-Bautista Elvira Roda Lorena Conte-Perales Rafael Franco Peter McCormick José L. Labandeira-García José L. Lanciego |
| author_sort | Natasha Luquin |
| collection | DOAJ |
| description | The A2AR 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 A2ARs 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 A2ARs 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 A2ARs failed to detect A2AR-positive neurons in the GPi and SNr, however, in situ hybridization showed that A2AR 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 A2AR 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 A2ARs 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. |
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| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T14:52:22Z |
| publishDate | 2012-09-01 |
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| series | Neurobiology of Disease |
| spelling | doaj.art-2c44aac8f5424673bf2f1dde257e67372022-12-21T23:41:18ZengElsevierNeurobiology of Disease1095-953X2012-09-01473347357Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB)Natasha Luquin0Salvador Sierra1Alberto J. Rico2Virginia Gómez-Bautista3Elvira Roda4Lorena Conte-Perales5Rafael Franco6Peter McCormick7José L. Labandeira-García8José L. Lanciego9Neurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra Medical College, Pamplona, Spain; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainNeurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra Medical College, Pamplona, Spain; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainNeurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra Medical College, Pamplona, Spain; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainNeurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra Medical College, Pamplona, Spain; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainNeurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra Medical College, Pamplona, Spain; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainNeurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra Medical College, Pamplona, Spain; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainNeurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra Medical College, Pamplona, Spain; Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, SpainNetwork Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, SpainNetwork Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Department of Morphological Sciences, University of Santiago de Compostela, Santiago de Compostela, SpainNeurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra Medical College, Pamplona, Spain; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Corresponding author at: Neurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra, Pio XII Avenue 55, 31008 Pamplona, Spain. Fax: +34 948 194 715.The A2AR 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 A2ARs 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 A2ARs 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 A2ARs failed to detect A2AR-positive neurons in the GPi and SNr, however, in situ hybridization showed that A2AR 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 A2AR 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 A2ARs 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.http://www.sciencedirect.com/science/article/pii/S0969996112001921GPCRsBasal gangliaGlobus pallidusSubstantia nigraRetrograde tracingParkinson disease |
| spellingShingle | Natasha Luquin Salvador Sierra Alberto J. Rico Virginia Gómez-Bautista Elvira Roda Lorena Conte-Perales Rafael Franco Peter McCormick José L. Labandeira-García José L. Lanciego Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB) Neurobiology of Disease GPCRs Basal ganglia Globus pallidus Substantia nigra Retrograde tracing Parkinson disease |
| title | Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB) |
| title_full | Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB) |
| title_fullStr | Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB) |
| title_full_unstemmed | Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB) |
| title_short | Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB) |
| title_sort | unmasking adenosine 2a receptors a2ars in monkey basal ganglia output neurons using cholera toxin subunit b ctb |
| topic | GPCRs Basal ganglia Globus pallidus Substantia nigra Retrograde tracing Parkinson disease |
| url | http://www.sciencedirect.com/science/article/pii/S0969996112001921 |
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