RT Journal Article
SR Electronic
T1 A Dual Role of Adenosine A<sub>2A</sub> Receptors in 3-Nitropropionic  Acid-Induced Striatal Lesions: Implications for the Neuroprotective Potential  of A<sub>2A</sub> Antagonists
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5361
OP 5369
DO 10.1523/JNEUROSCI.23-12-05361.2003
VO 23
IS 12
A1 Blum, David
A1 Galas, Marie-Christine
A1 Pintor, Annita
A1 Brouillet, Emmanuel
A1 Ledent, Catherine
A1 Muller, Christa E.
A1 Bantubungi, Kadiombo
A1 Galluzzo, Mariangela
A1 Gall, David
A1 Cuvelier, Laetitia
A1 Rolland, Anne-Sophie
A1 Popoli, Patrizia
A1 Schiffmann, Serge N.
YR 2003
UL http://www.jneurosci.org/content/23/12/5361.abstract
AB 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.