Objective: Neuronal atrophy and/or cell death occurs during the course of normal aging and is accelerated during neurodegenerative diseases such as Alzheimer’s disease (AD). Oxidative stress, which causes oxidation of biological targets, results in cell death resulting from apoptosis and necrosis depending on the flux and the time of exposure. Clinical studies have demonstrated that atypical antipsychotics such as quetiapine and olanzapine are safe and effective in the treatment of AD patients with behavioral disturbances and psychotic symptoms. In the present study, we investigated the ability of quetiapine and other atypical antipsychotics to prevent 1-methyl-4-phenylpyridinium (MPP+)- and b-amyloid (25-35)-induced cell death in PC12 cells.
Design: The PC12 cell line was cultured in RPMI 1640 medium containing 5% newborn calf serum and 10% horse serum plus 100 units/mL penicillin. PC12 cells were treated with vehicle or increasing concentrations of quetiapine (10–100 mM), olanzapine (50–200 mM), or clozapine (20–100 mM) before the induction of neurodegeneration. Neurodegeneration was produced by the addition of MPP+ (50 mM) or b-amyloid (25-35) (1, 10, and 25 mM) to the culture medium. To determine cell survival, PC12 cells were seeded at a density of 4 x 104 to 5 x 104 cells per well on collagen-coated 96-well plates in 100 mL of culture medium.
Materials and Methods: Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction assay.
Results: After exposure to MPP+ or increasing concentrations of b-amyloid (25-35), cell viability decreased; pretreatment with quetiapine and other atypical antipsychotics attenuated the decrease in cell viability. Quetiapine, clozapine, and olanzapine attenuated PC12 cell death after treatment with MPP+. Quetiapine and olanzapine attenuated neurotoxicity after treatment with aged b-amyloid (25-35), and quetiapine also attenuated neurotoxicity after treatment with fresh b-amyloid (25-35).
Conclusion: Our data suggest that these atypical antipsychotics may have neuroprotective potential to slow down the process of neurodegeneration in patients with AD or other neurodegenerative disorders.
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