Neuroprotective effect of acute and chronic administration of copper (II) sulfate against MPP+ neurotoxicity in mice

Neurodegenerative effects of MPP+, the main metabolite of MPTP include dopamine (DA) depletion and enhanced lipid peroxidation (LPO) in mice striata, both associated to free radicals overproduction. Since copper is related to several antioxidant enzymes, we tested its neuroprotective effect against MPP+-induced neurotoxicity (20 mug/3 mul). CuSO4 pretreatment was administrated by either acute (2.5 mg/kg, i.p) or chronic (350 or 700 mg/l doses through drinking water, for 30 days) schemes. Acute administration blocked MPP+-induced striatal LPO only when administered 16 or 24 hours before MPP+, and prevented the DA-depleting effect only at 24 hours. Chronic CuSO4 prevented the LPO increase, and blocked the DA depletion only at the higher dose used (700 mg/l). Neuroprotective effect of CuSO4 was dependent on the dose and the time of pretreatment, which suggest that this lag could be related with mechanisms of activation or synthesis of copper-dependent proteins responsible of cellular defense against MPP+.