Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1.
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.
Souza
Bruno R
BR
Laboratório de Neurociências, Departamento de Saúde Mental, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av Alfredo Balena 190, Belo Horizonte, MG, Brazil.
Torres
Karen C L
KC
Miranda
Débora M
DM
Motta
Bernardo S
BS
Scotti-Muzzi
Estêvão
E
Guimarães
Melissa M
MM
Carneiro
Daniel S
DS
Rosa
Daniela V F
DV
Souza
Renan P
RP
Reis
Helton J
HJ
Jeromin
Andreas
A
Romano-Silva
Marco A
MA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002999:Clone Cells; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D051580:Neuronal Calcium-Sensor Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
D014150:Antipsychotic Agents; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C497930:Ppp1r1b protein, rat; C101464:frequenin calcium sensor proteins