| Autor: |
Blum, David, Galas, Marie-Christine, Pintor, Annita, Brouillet, Emmanuel, Ledent, Catherine, Muller, Christa E., Bantubungi, Kadiombo, Galluzzo, Mariangela, Gall, David, Cuvelier, Laetitia, Rolland, Anne-Sophie, Popoli, Patrizia, Schiffmann, Serge N. |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 6/15/2003, Vol. 23 Issue 12, p5361, 9p |
| Abstrakt: |
Reduction of A[sub2A] 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[sub2A] receptors has been found in striatal cells prone to degenerate in experimental models of this neurodegenerative disease. However, the role of A[sub2A] receptors in the pathogenesis of HD remains obscure. In the present study, using A[sub2A][sup-/-] mice and pharmacological compounds in rat, we demonstrate that striatal neurodegeneration induced by the mitochondrial toxin 3-nitropropionic acid (3NP) is regulated by A[sub2A] receptors. Our results show that the striatal outcome induced by 3NP depends on a balance between the deleterious activity of presynaptic A[sub2A] receptors and the protective activity of postsynaptic A[sub2A] receptors. Moreover, microdialysis data demonstrate that this balance is anatomically determined, because the A[sub2A] presynaptic control on striatal glutamate release is absent within the posterior striatum. Therefore, because blockade of A[sub2A] 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[sub2A] antagonists in Huntington's as well as in other neurodegenerative diseases could exhibit undesirable biphasic neuroprotective-neurotoxic effects. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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