Research

Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1

Bruno R Souza¹ , Karen CL Torres¹ , Débora M Miranda¹ , Bernardo S Motta¹ , Estêvão Scotti-Muzzi¹ , Melissa M Guimarães¹ , Daniel S Carneiro¹ , Daniela VF Rosa¹ , Renan P Souza¹ , Helton J Reis² , Andreas Jeromin³ and Marco A Romano-Silva¹

¹  Laboratório de Neurociências, Departamento de Saúde Mental, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av Alfredo Balena 190, 30130-100, Belo Horizonte, MG, Brazil

²  Departamento de Farmacologia, instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil

³  Banyan Biomarkers, Inc., Alachua, FL 32615, USA

author email corresponding author email

Journal of Negative Results in BioMedicine 2010, 9:4doi:10.1186/1477-5751-9-4

Published:	19 June 2010

Abstract

Background

Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D₂. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC): Neuronal Calcium Sensor-1 (NCS-1) and DARPP-32. NCS-1, which is upregulated in PFC of schizophrenics, inhibits D₂ internalization. DARPP-32, which is decreased in PFC of schizophrenics, is a key downstream effector in transducing dopamine signaling. We previously demonstrated that antipsychotics do not change levels of both proteins in rat's brain. However, since NCS-1 and DARPP-32 levels are not altered in wild type rats, we treated wild type PC12 cells (PC12 WT) and PC12 cells stably overexpressing NCS-1 (PC12 Clone) with antipsychotics to investigate if NCS-1 upregulation modulates DARPP-32 expression in response to antipsychotics treatment.

Results

We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol) or atypical (Clozapine and Risperidone) antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments.

Conclusions

Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.