Differential effects of olanzapine on the gene expression of superoxide dismutase and the low affinity nerve growth factor receptor.

Neuroanatomical studies of schizophrenia suggest that progressive neuropathological changes (such as neuronal atrophy and/or cell death) occur over the lifetime course of the disease. Early intervention with atypical neuroleptics has been shown to prevent progression of at least some symptoms, although the mechanisms by which neuroleptics may do this remain unknown. In this study, PC12 cells were used to determine the effects of the new atypical antipsychotic olanzapine on the gene expression of superoxide dismutase (SOD1) and the low affinity nerve growth factor receptor (p75). The results show that olanzapine increases SOD1 at concentrations of 10 and 100 microM after 48 hr of incubation in PC12 cultures. The treatment decreases p75 gene expression at concentrations 100 microM after 48 hr of incubation. Since both the upregulation of SOD1 mRNA and the antisense blockade of p75 mRNA have been associated with reduced cell death, our results suggest that olanzapine has neuroprotective potential and thus may be useful in preventing further neurodegeneration accompanying schizophrenia.