A2A adenosine receptor antagonists protect the striatum against rotenone-induced neurotoxicity.
Adenosine A2A receptor has emerged as an attractive non-dopaminergic target in the experimental pharmacological therapy for Parkinson's disease (PD). Moreover, it has been postulated that A2A adenosine receptor antagonists exert neuroprotective effects in experimental models of PD and progressive supranuclear palsy (PSP). Interestingly, in both these pathological conditions a deficit of mitochondrial complex I has been found. Thus, utilizing extracellular and intracellular recordings from corticostriatal brain slices, we have tested the possible neuroprotective action of two A2A receptor antagonists, ST1535 and ZM241385, on the irreversible electrophysiological effects induced by the acute application of rotenone, a pesticide acting as a selective inhibitor of mitochondrial complex I activity. Both these antagonists reduced the rotenone-induced loss of corticostriatal field potential amplitude as well as the membrane depolarization caused by this toxin on striatal spiny neurons. The use of A2A receptor antagonists might represent a promising neuroprotective strategy in basal ganglia disorders involving a deficit of mitochondrial complex I activity.
Clinica Neurologia, Università di Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy.
Vincenzo
V
Belcastro
Alessandro
A
Tozzi
Michela
M
Tantucci
Cinzia
C
Costa
Massimiliano
M
Di Filippo
Alessia
A
Autuori
Barbara
B
Picconi
Sabrina
S
Siliquini
Elisa
E
Luchetti
Franco
F
Borsini
Paolo
P
Calabresi
D000200:Action Potentials / Q000187:drug effects; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000633:toxicity*; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
C506291:2-n-butyl-9-methyl-8-(1,2,3)triazol-2-yl-9H-purin-6-ylamine; D058917:Adenosine A2 Receptor Antagonists; D007306:Insecticides; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D012402:Rotenone; D000225:Adenine