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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2003-6-30
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pubmed:abstractText |
Reduction of A2A 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 A2A receptors has been found in striatal cells prone to degenerate in experimental models of this neurodegenerative disease. However, the role of A2A receptors in the pathogenesis of HD remains obscure. In the present study, using A2A-/- mice and pharmacological compounds in rat, we demonstrate that striatal neurodegeneration induced by the mitochondrial toxin 3-nitropropionic acid (3NP) is regulated by A2A receptors. Our results show that the striatal outcome induced by 3NP depends on a balance between the deleterious activity of presynaptic A2A receptors and the protective activity of postsynaptic A2A receptors. Moreover, microdialysis data demonstrate that this balance is anatomically determined, because the A2A presynaptic control on striatal glutamate release is absent within the posterior striatum. Therefore, because blockade of A2A receptors has differential effects on striatal cell death in vivo depending on its ability to modulate presynaptic over postsynaptic receptor activity, therapeutic use of A2A antagonists in Huntington's as well as in other neurodegenerative diseases could exhibit undesirable biphasic neuroprotective-neurotoxic effects.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-(2-carboxyethyl)phenethylamino)...,
http://linkedlifedata.com/resource/pubmed/chemical/3-nitropropionic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/MSX 3 compound,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Nitro Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Phenethylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Propionic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Adenosine A2A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P1,
http://linkedlifedata.com/resource/pubmed/chemical/Xanthines
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1529-2401
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pubmed:author |
pubmed-author:BantubungiKadiomboK,
pubmed-author:BlumDavidD,
pubmed-author:BrouilletEmmanuelE,
pubmed-author:CuvelierLaetitiaL,
pubmed-author:GalasMarie-ChristineMC,
pubmed-author:GallDavidD,
pubmed-author:GalluzzoMariangelaM,
pubmed-author:LedentCatherineC,
pubmed-author:MullerChrista ECE,
pubmed-author:PintorAnnitaA,
pubmed-author:PopoliPatriziaP,
pubmed-author:RollandAnne-SophieAS,
pubmed-author:SchiffmannSerge NSN
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5361-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12832562-Adenosine,
pubmed-meshheading:12832562-Animals,
pubmed-meshheading:12832562-Body Weight,
pubmed-meshheading:12832562-Cell Death,
pubmed-meshheading:12832562-Corpus Striatum,
pubmed-meshheading:12832562-Disease Models, Animal,
pubmed-meshheading:12832562-Drug Administration Schedule,
pubmed-meshheading:12832562-Encephalitis,
pubmed-meshheading:12832562-Genetic Predisposition to Disease,
pubmed-meshheading:12832562-Glutamic Acid,
pubmed-meshheading:12832562-Huntington Disease,
pubmed-meshheading:12832562-Male,
pubmed-meshheading:12832562-Mice,
pubmed-meshheading:12832562-Mice, Knockout,
pubmed-meshheading:12832562-Neuroprotective Agents,
pubmed-meshheading:12832562-Nitro Compounds,
pubmed-meshheading:12832562-Phenethylamines,
pubmed-meshheading:12832562-Propionic Acids,
pubmed-meshheading:12832562-RNA, Messenger,
pubmed-meshheading:12832562-Rats,
pubmed-meshheading:12832562-Rats, Inbred Lew,
pubmed-meshheading:12832562-Rats, Wistar,
pubmed-meshheading:12832562-Receptor, Adenosine A2A,
pubmed-meshheading:12832562-Receptors, Purinergic P1,
pubmed-meshheading:12832562-Signal Transduction,
pubmed-meshheading:12832562-Survival Rate,
pubmed-meshheading:12832562-Synapses,
pubmed-meshheading:12832562-Xanthines
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pubmed:year |
2003
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pubmed:articleTitle |
A dual role of adenosine A2A receptors in 3-nitropropionic acid-induced striatal lesions: implications for the neuroprotective potential of A2A antagonists.
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pubmed:affiliation |
Laboratory of Neurophysiology, CP601, Université Libre de Bruxelles-Erasme, 1070 Brussels, Belgium. dablum@ulb.ac.be
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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