A dual role of adenosine A2A receptors in 3-nitropropionic acid-induced striatal lesions: implications for the neuroprotective potential of A2A antagonists.

摘要: Reduction of A2A receptor expression is one the earliest events occurring in both Huntington's disease (HD) patients and mice overexpressing N-terminal part mutated huntingtin. Interestingly, increased activity receptors has been found striatal cells prone to degenerate experimental models this neurodegenerative disease. However, role pathogenesis HD remains obscure. In present study, using A2A-/- pharmacological compounds rat, we demonstrate that neurodegeneration induced by mitochondrial toxin 3-nitropropionic acid (3NP) regulated receptors. Our results show outcome 3NP depends on a balance between deleterious presynaptic protective postsynaptic Moreover, microdialysis data anatomically determined, because control glutamate release absent within posterior striatum. Therefore, blockade differential effects cell death vivo depending its ability modulate over activity, therapeutic use antagonists as well other diseases could exhibit undesirable biphasic neuroprotective-neurotoxic effects.