QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 15, 2003, 23(12):5361-5369

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (47) Citing Articles via Google Scholar Google Scholar Articles by Blum, D. Articles by Schiffmann, S. N. Search for Related Content PubMed PubMed Citation Articles by Blum, D. Articles by Schiffmann, S. N. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB 3-NITROPROPIONIC ACID GLUTAMIC ACID HYDROCHLORIDE Medline Plus Health Information Huntington's Disease Hurricanes

 Previous Article  |  Next Article 

A Dual Role of Adenosine A_2A Receptors in 3-Nitropropionic Acid-Induced Striatal Lesions: Implications for the Neuroprotective Potential of A_2A Antagonists

David Blum,¹ Marie-Christine Galas,^1 * Annita Pintor,^3 * Emmanuel Brouillet,⁴ Catherine Ledent,² Christa E. Muller,⁵ Kadiombo Bantubungi,¹ Mariangela Galluzzo,³ David Gall,¹ Laetitia Cuvelier,¹ Anne-Sophie Rolland,¹ Patrizia Popoli,³ and Serge N. Schiffmann¹

¹ Laboratory of Neurophysiology, CP601, and ²Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles-Erasme, 1070 Brussels, Belgium, ³Department of Pharmacology, Istituto Superiore di Sanita, 00161 Rome, Italy, ⁴Unité de Recherche Associée—Commissariat à l'Energie Atomique—Centre National de la Recherche Scientifique 2210, Service Hospitalier Frédéric Joliot, Département de la Recherche Médicale, Commissariat à l'Energie Atomique, 91406 Orsay, France, and ⁵Universitaet Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie, Poppelsdorf, D-53115 Bonn, Germany

Reduction of A_2A receptor expression is one of the earliest events occurring in both Huntington's disease (HD) patients and mice overexpressing the N-terminal part of mutated huntingtin. Interestingly, increased activity of A_2A receptors has been found in striatal cells prone to degenerate in experimental models of this neurodegenerative disease. However, the role of A_2A receptors in the pathogenesis of HD remains obscure. In the present study, using A_2A^-/- mice and pharmacological compounds in rat, we demonstrate that striatal neurodegeneration induced by the mitochondrial toxin 3-nitropropionic acid (3NP) is regulated by A_2A receptors. Our results show that the striatal outcome induced by 3NP depends on a balance between the deleterious activity of presynaptic A_2A receptors and the protective activity of postsynaptic A_2A receptors. Moreover, microdialysis data demonstrate that this balance is anatomically determined, because the A_2A presynaptic control on striatal glutamate release is absent within the posterior striatum. Therefore, because blockade of A_2A receptors has differential effects on striatal cell death in vivo depending on its ability to modulate presynaptic over postsynaptic receptor activity, therapeutic use of A_2A antagonists in Huntington's as well as in other neurodegenerative diseases could exhibit undesirable biphasic neuroprotective—neurotoxic effects.

Key words: 3-nitropropionic; Huntington's disease; striatum; A_2A receptors; neuroprotection; cell death

---

Received Jan. 23, 2003; revised Mar. 19, 2003; accepted Apr. 7, 2003.

This article has been cited by other articles:

				M.-C. Chiang, H.-M. Chen, H.-L. Lai, H.-W. Chen, S.-Y. Chou, C.-M. Chen, F.-J. Tsai, and Y. Chern The A2A adenosine receptor rescues the urea cycle deficiency of Huntington's disease by enhancing the activity of the ubiquitin-proteasome system Hum. Mol. Genet., August 15, 2009; 18(16): 2929 - 2942. [Abstract] [Full Text] [PDF]

				I A. S Olsson, A. K Hansen, and P. Sandoe Animal welfare and the refinement of neuroscience research methods - a case study of Huntington's disease models Lab Anim, July 1, 2008; 42(3): 277 - 283. [Abstract] [Full Text] [PDF]

				Q.-Y. Huang, C. Wei, L. Yu, J. E. Coelho, H.-Y. Shen, A. Kalda, J. Linden, and J.-F. Chen Adenosine A2A Receptors in Bone Marrow-Derived Cells But Not in Forebrain Neurons Are Important Contributors to 3-Nitropropionic Acid-Induced Striatal Damage as Revealed by Cell-Type-Selective Inactivation. J. Neurosci., November 1, 2006; 26(44): 11371 - 11378. [Abstract] [Full Text] [PDF]

				C. Jacquard, Y. Trioulier, F. Cosker, C. Escartin, N. Bizat, P. Hantraye, J. M. Cancela, G. Bonvento, and E. Brouillet Brain mitochondrial defects amplify intracellular [Ca2+] rise and neurodegeneration but not Ca2+ entry during NMDA receptor activation FASEB J, May 1, 2006; 20(7): 1021 - 1023. [Abstract] [Full Text] [PDF]

				M.-C. Chiang, Y.-C. Lee, C.-L. Huang, and Y. Chern cAMP-response Element-binding Protein Contributes to Suppression of the A2A Adenosine Receptor Promoter by Mutant Huntingtin with Expanded Polyglutamine Residues J. Biol. Chem., April 8, 2005; 280(14): 14331 - 14340. [Abstract] [Full Text] [PDF]

				O. P Dall'Igna, D. O Souza, and D. R Lara Caffeine as a Neuroprotective Adenosine Receptor Antagonist Ann. Pharmacother., April 1, 2004; 38(4): 717 - 718. [Full Text] [PDF]

				P. D. Alfinito, S.-P. Wang, L. Manzino, S. Rijhsinghani, G. D. Zeevalk, and P. K. Sonsalla Adenosinergic Protection of Dopaminergic and GABAergic Neurons against Mitochondrial Inhibition through Receptors Located in the Substantia Nigra and Striatum, Respectively J. Neurosci., November 26, 2003; 23(34): 10982 - 10987. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help