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 neuropath ological changes (such as neuronal atrophy and/or cell death) occur over th e lifetime course of the disease. Early intervention with atypical neurolep tics has been shown to prevent progression of at least some symptoms, altho ugh the mechanisms by which neuroleptics may do this remain unknown. In thi s study, PC12 cells were used to determine the effects of the new atypical antipsychotic olanzapine on the gene expression of superoxide dismutase (SO D1) and the low affinity nerve growth factor receptor (p75), The results sh ow that olanzapine increases SOD1 at concentrations of 10 and 100 mu M afte r 48 hr of incubation in PC12 cultures. The treatment decreases p75 gene ex pression at concentrations 100 mu M after 48 hr of incubation. Since both t he upregulation of SOD1 mRNA and the antisense blockade of p75 mRNA have be en associated with reduced cell death, our results suggest that olanzapine has neuroprotective potential and thus may be useful in preventing further neurodegeneration accompanying schizophrenia. J, Neurosci, Res. 56:72-75, 1 999. (C) 1999 Wiley-Liss, Inc.