Paliperidone protects SK-N-SH cells against glutamate toxicity via Akt1/GSK3β signaling pathway

  • Schizophr Res. 2014 Aug;157(1-3):120-7. doi: 10.1016/j.schres.2014.05.037.
Lei Peng  1 ,  Xingzhen Zhang  1 ,  Xianping Cui  2 ,  Dexiao Zhu  1 ,  Jintao Wu  1 ,  Dong Sun  3 ,  Qingwei Yue  1 ,  Zeyan Li  1 ,  Haili Liu  1 ,  Guibao Li  1 ,  Jing Zhang  1 ,  Hongyan Xu  3 ,  Fuchen Liu  4 ,  Chengkun Qin  2 ,  Mingfeng Li  4 ,  Jinhao Sun  5
Affiliations
  • 1. Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
  • 2. Department of General Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250012, PR China.
  • 3. Experimental Platform for Medical Function, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
  • 4. Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
  • 5. Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China. Electronic address: [email protected].
PMID: 24962437 DOI: 10.1016/j.schres.2014.05.037
Abstract

Schizophrenia is a heterogeneous psychotic illness and its etiology remains poorly understood. Recent studies have suggested that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics appear to slow progressive morphological brain changes. In addition, the atypical antipsychotics were reported to have a superior therapeutic efficacy in treating schizophrenia and have a low incidence of extrapyramidal side effects (EPS) compared to typical antipsychotics. However, the mechanisms of atypical antipsychotics in treating schizophrenia and the basis for differences in their clinical effects were still totally unknown. In the present study, we investigated whether paliperidone shows protective effects on SK-N-SH cells from cell toxicity induced by exposure to glutamate. We examined the effects of the drugs on cell viability (measured by MTT metabolism assay and Lactate Dehydrogenase (LDH) activity assay), Apoptosis rate, ROS levels and gene expression and phosphorylation of Akt1 and GSK3β. The results showed that paliperidone significantly increases the cell viability by MTT and LDH assays (p<0.05), in contrast to the typical antipsychotic (haloperidol), which had little neuroprotective activity. Moreover, paliperidone retarded the glutamate-mediated promotion of ROS and the rate of Apoptosis (p<0.05). In addition, paliperidone also effectively reversed glutamate-induced decreases of gene expression and phosphorylation of Akt1 and GSK3β (both p<0.05). Our results demonstrated that paliperidone could effectively protect SK-N-SH cells from glutamate-induced damages via Akt1/GSK3β signaling pathway.

Keywords
Glutamate; Paliperidone; Protection; SK-N-SH; Schizophrenia.
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