A2A adenosine receptor antagonists protect the striatum against rotenone-induced neurotoxicity

Vincenzo Belcastro, Alessandro Tozzi, Michela Tantucci, Cinzia Costa, Massimiliano Di Filippo, Alessia Autuori, Barbara Picconi, Sabrina Siliquini, Elisa Luchetti, Franco Borsini, Paolo Calabresi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)231-234
Number of pages4
JournalExperimental Neurology
Volume217
Issue number1
DOIs
Publication statusPublished - May 2009

Keywords

  • A2A receptor
  • Adenosine
  • Neuroprotection
  • Rotenone
  • Striatum

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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