INVOLVEMENT OF IRON IN MPP-NIGRA - PROTECTION BY DESFERRIOXAMINE( TOXICITY IN SUBSTANTIA)

Desferrioxamine (DES) protective effect against 1-methyl-4-phenylpyrid inium (MPP+) toxicity was evaluated by microdialysis in the substantia nigra. DES (1 mu M to 10 mM) co-perfused with MPP+ (2.5 mM) on day 1, produced on day 2 a higher dopamine extracellular output after perfus ion of MPP+ than in control-MPP+ perfusion experiments, in which no DE S was administered on day 1. Both Ringer's perfusion alone (control-Ri nger) and co-perfusion of DES (10 mM) with MPP+ (2.5 mM) on day 1 prod uced on day 2 similar increases in dopamine extracellular output after a second MPP+ perfusion. In the control-Ringer experiment, note that the MPP+ on day 2 is the first MPP+ perfusion. Perfusion of FeCl3 (200 mu M) along with MPP+ (2.5 mM) and DES (100 mu M) on day 1 completely abolished on day 2 the neuroprotective effect found with MPP+ (2.5 mM ) and DES (100 mu M). The ability of DES to protect against MPP+ toxic ity may indicate a therapeutic strategy in the treatment of diseases w hen iron is implicated. (C) 1997 Elsevier Science B.V.