cytochrome-c-t and Schizophrenia

The aim of this study was to investigate the neurotoxic effects of Fe. We designed CMN loaded superparamagnetic iron oxide nanoparticles (SPIONs) (Fe. We showed that effective treatment with CMN reduced or prevented Fe. Taken together, Fe

Topics: Adenosine Triphosphate; Animals; Behavior Rating Scale; Cerebellum; Curcumin; Cytochromes c; Disease Models, Animal; Magnetite Nanoparticles; Male; Membrane Potential, Mitochondrial; Mitochondria; Neuroprotection; Neuroprotective Agents; Random Allocation; Rats; Rats, Wistar; Reactive Oxygen Species; Schizophrenia

Chlorpromazine (CPZ) is a widely used antipsychotic drug with antagonistic effect on dopamine receptors. Accumulating evidence has shown that CPZ plays a neuroprotective role in various models of toxicity and apoptosis. However, the underlying mechanism contributing to this protective effect remains unclear. Here, we evaluate the effect of CPZ on mitochondrial apoptotic pathway in the neuron system. Higher levels of B-cell lymphoma-2 (Bcl-2) and tissue factor (TF) but lower apoptotic rate were found in hippocampus of CPZ-treated schizophrenic patients compared with non-antipsychotic treated controls. Additionally, both short-term and long-term treatment of CPZ in rats could up-regulate the levels of Bcl-2 and TF with no cytotoxic effects. In the in vitro experiment, expression of Bcl-2 was up-regulated in the C6 glioma cells transfected with pEGFP-N1-TF recombinant plasmid. Furthermore, in another independent rat model of apoptosis, compared with the group administrated with alcohol only, the brains of the CPZ-pretreated rats showed lower expression of cleaved caspase-3, cytochrome c and Bax, but higher expression of Bcl-2 and TF. Our data demonstrate that CPZ exerts its neuronal protective effects through inhibiting the activation of mitochondrial apoptotic pathway by up-regulating TF expression, thus providing new insight into CPZ function and application.

Topics: Adult; Aged; Animals; Antipsychotic Agents; Apoptosis; Autopsy; bcl-2-Associated X Protein; Case-Control Studies; Caspase 3; Chlorpromazine; Cytochromes c; Gene Expression Regulation; Hippocampus; Humans; Male; Middle Aged; Mitochondria; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Schizophrenia; Thromboplastin