Protective effects of atypical antipsychotic drugs on PC12 cells after serum withdrawal.
Atypical antipsychotic drugs are widely used in the treatment of schizophrenia, and clinical evidence has shown that early and prolonged intervention with these drugs will improve the long-term outcome. It is still unclear, however, whether the atypical antipsychotic drugs are also neuroprotective. To clarify this matter, we used PC12 cell cultures and the MTT assay for cell viability to determine whether various concentrations of the atypical antipsychotics clozapine, quetiapine, and risperidone are neuroprotective after serum withdrawal. In addition, to explore the drugs' actions, Northern blot was used to examine the gene expression of SOD1 (Cu/Zn superoxide dismutase) and p75NTR (p75 neurotrophin receptor). The results demonstrated that 1) the antipsychotic drugs can protect PC12 cells from death after serum withdrawal; cell viability in these drug treatment groups is significantly different from that in the groups without serum in the medium (P < 0.01); and 2) these drugs up-regulated the SOD1 gene expression to more than 120% (P < 0.05) and also down-regulated p75NTR mRNA levels to less than 65% of their respective control values (P < 0.05). These findings suggest that the atypical antipsychotics clozapine, quetiapine, and risperidone may exert a neuroprotective function through the modulation of SOD1 and p75NTR expression.
Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Ou
O
Bai
Zelan
Z
Wei
Wenfu
W
Lu
Rudy
R
Bowen
David
D
Keegan
Xin-Min
XM
Li
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology*; D003987:Dibenzothiazepines / Q000494:pharmacology*; D016716:PC12 Cells; D000069348:Quetiapine Fumarate; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D018967:Risperidone / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D000072105:Superoxide Dismutase-1
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D000069348:Quetiapine Fumarate; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003024:Clozapine; D018967:Risperidone