Abstract
BackgroundSchizophrenia 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.ResultsWe 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.ConclusionsBecause 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.
Highlights
Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown
PC12 cells were prepared to examine Neuronal Calcium Sensor-1 (NCS-1) protein expression after drug treatment and it was observed no changes in NCS-1 levels in both PC12 cells wild type (PC12 WT) (Figure 1A and 1C) [One Way ANOVA; P = 0.919] and PC12 Clone cells (Figure 1B and 1D) [One Way ANOVA; P = 0.936] after chronic treatment with either typical or atypical antipsychotics
These results suggest that normal and upregulated levels of NCS-1 are not modulated by chronic antipsychotic treatments
Summary
Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. 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 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. Recent studies have demonstrated change in the expression of two proteins involved with dopaminergic signaling modulation in the schizophrenics PFC [9,10,11] It was reported decrease of dopamine and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein of relative molecular mass 32,000 (DARPP-32) and upregulation of Neuronal Calcium Sensor-1 (NCS-1) expression [12,13]
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