title: Paliperidone protects SK-N-SH cells against glutamate toxicity via Akt1/GSK3β signaling pathway.
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.
authors: Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Lei
authors: L
authors: Peng
authors: Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Xingzhen
authors: X
authors: Zhang
authors: Department of General Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250012, PR China.
authors: Xianping
authors: X
authors: Cui
authors: Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Dexiao
authors: D
authors: Zhu
authors: Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Jintao
authors: J
authors: Wu
authors: Experimental Platform for Medical Function, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Dong
authors: D
authors: Sun
authors: Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Qingwei
authors: Q
authors: Yue
authors: Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Zeyan
authors: Z
authors: Li
authors: Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Haili
authors: H
authors: Liu
authors: Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Guibao
authors: G
authors: Li
authors: Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Jing
authors: J
authors: Zhang
authors: Experimental Platform for Medical Function, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
authors: Hongyan
authors: H
authors: Xu
authors: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors: Fuchen
authors: F
authors: Liu
authors: Department of General Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250012, PR China.
authors: Chengkun
authors: C
authors: Qin
authors: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors: Mingfeng
authors: M
authors: Li
authors: Department of Anatomy and Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China. Electronic address: sunjinhao@sdu.edu.cn.
authors: Jinhao
authors: J
authors: Sun
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D049108:Cell Enlargement / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000068882:Paliperidone Palmitate; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D009025:Morpholines; D018696:Neuroprotective Agents; D011743:Pyrimidines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; C494918:AKT1 protein, human; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D006220:Haloperidol; D000068882:Paliperidone Palmitate
keywords: Glutamate; Paliperidone; Protection; SK-N-SH; Schizophrenia