Abstract
Schizophrenia is a severe, chronic mental illness characterized by delusions, hallucinations, negative symptoms, and cognitive dysfunction. Recently, several studies have demonstrated that the pathogenesis of schizophrenia involves mitochondrial dysfunction and oxidative stress. However, the effect of antipsychotic drugs for these events has been poorly investigated. In the present study, we evaluated the neuroprotective effect of an atypical antipsychotic drug, ziprasidone (ZPD), on rotenone (ROT)-induced neurotoxicity involving oxidative stress in PC12 cells. Our data showed that ZPD treatment promoted the translocation of NF-E2-related factor-2 (Nrf2) from cytoplasm to nucleus and activated the expression of its target genes NAD(P)H quinone oxidoreductase (NQO-1), catalase (CAT), and heme oxygenase (HO-1). Additionally, ZPD prevented ROT-induced cell death and intracellular reactive oxygen species production. Interestingly, the use of serotonin 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4 (4-(2-phtalimido) butyl) piperazine (NAN-190) completely blocked the protective effect of ZPD against ROT-induced cell death. Our results demonstrate the neuroprotective effect of ZPD against ROT-induced neurotoxicity and suggest that ZPD may be a potential candidate for the prevention of mitochondrial dysfunction and oxidative stress in schizophrenia.
Highlights
Schizophrenia is a mental disorder characterized by the occurrence of psychotic symptoms, including hallucinations and delusions [1,2,3]
We investigated atypical of antipsychotic drug ZPD imparts for the neuroprotective effectswhether leading tothe the prevention mitochondrial dysfunction and reduction oxidative stress have not been elucidated ziprasidone (ZPD),neuronal an atypicalPC12 cells
Our results suggest that the neuroprotective effect of ZPD through the effect on mitochondrial dysfunction and oxidative stress is mediated via 5-HT1A -R
Summary
Schizophrenia is a mental disorder characterized by the occurrence of psychotic symptoms, including hallucinations and delusions [1,2,3]. It is prevalent in 1% of the global population and usually emerges in early adulthood [2,4]. Many causes of schizophrenia have been elucidated; the most convincing is the dopamine hypothesis [5], which has been the basis for the development and clinical administration of many antipsychotic medications [6]. Recent evidence suggests that oxidative stress may play an important role in the pathophysiology of schizophrenia [7,8,9]. Oxidative stress refers to an imbalance of free radicals, such as reactive oxygen species (ROS), which are generated from both normal metabolic processes involving neurotransmitters
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