APPARENT ANTIOXIDANT EFFECT OF 1-DEPRENYL ON HYDROXYL RADICAL FORMATION AND NIGRAL INJURY ELICITED BY MPP+ IN-VIVO

Using a modified microdialysis procedure, we confirmed that intrastriatal administration of 1-methyl-4-phenylpyridinium ion (MPP+) induced a sustained overflow of dopamine accompanied by increased formation of hydroxyl free radicals (.OH) as reflected by salicylate hydroxylation. Pretreatment with 1-deprenyl (selegiline 60 pmol, intrastriatal perfusion) significantly decreased the .OH formation elicited by MPP+ (75 nmol). There was a small decrease of dopamine efflux and an insignificant change of the ratio of 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine following 1-deprenyl pretreatment. These in vivo findings support prior in vitro data that an unique antioxidant property of 1-deprenyl may be independent of its inhibition of type B monoamine oxidase. In addition, intranigral co-administration of 1-deprenyl (4.2 nmol) with MPP+ (4.2 nmol) completely protected nigral neurons from probable oxidative injuries induced by MPP+ (4.2 nmol), as reflected by a near 50% loss of striatal dopamine ipsilateral to the side of infusion of drug into the substantia nigra. This apparent neuroprotective effect of 1-deprenyl on midbrain nigral neurons was also confirmed by histological findings. The present in vivo data clearly demonstrate that 1-deprenyl can protect nigral neurons against dopamine neurotoxicity produced by MPP+, as suggested by an earlier in vitro study. Thus, 1-deprenyl can preserve the function of MPP+-damaged nigral neurons perhaps by its apparent antioxidant property in addition to its blockade of the bioactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium metabolites by type B monoamine oxidase.