NEUROPROTECTIVE EFFECT OF THE IRON CHELATOR DESFERRIOXAMINE AGAINST MPP(+) TOXICITY ON STRIATAL DOPAMINERGIC TERMINALS

Microdialysis was used to evaluate the effect of desferrioxamine (DES) against 1-methyl-4-phenylpyridinium (MPP(+)) toxicity. The presence o f DES (40 fmol-40 nmol/15 min for a total of 90 min) in the Ringer sol ution, coperfused with MPP(+) (40 nmol/15 min) on day 1, produced on d ay 2 a higher extracellular dopamine output after perfusion of MPP(+) than in control MPP(+) perfusion experiments, in which no DES was admi nistered on day 1. Both Ringer perfusion alone (control Ringer) and co perfusion of 40 nmol DES with 40 nmol MPP(+) on day 1 produced on day 2 similar increases in extracellular dopamine output after a second MP P(+) perfusion. In the control Ringer experiment, note that the MPP(+) on day 2 is the first MPP(+) perfusion. Perfusion of 800 fmol FeCl3/1 5 min along with 40 nmol MPP(+) and 400 fmol DES on day 1 completely a bolished on day 2 the neuroprotective effect found with 40 nmol MPP(+) and 400 fmol DES; 800 fmol FeCl3 did not increase the neurotoxic effe ct of 40 nmol MPP(+) perfusion. The ability of DES to protect against MPP(+) toxicity may indicate a therapeutic strategy in the treatment o f diseases when iron is implicated.