Paliperidone protects SK-N-SH cells against glutamate toxicity via Akt1/GSK3β signaling pathway
作者： Lei Peng , Xingzhen Zhang , Xianping Cui , Dexiao Zhu , Jintao Wu
DOI: 10.1016/J.SCHRES.2014.05.037
关键词: Viability assay 、 Neuroprotection 、 Paliperidone Palmitate 、 Anesthesia 、 Glutamate receptor 、 Haloperidol 、 Paliperidone 、 Medicine 、 Typical antipsychotic 、 Apoptosis 、 Pharmacology
摘要: Schizophrenia is a heterogeneous psychotic illness and its etiology remains poorly understood. Recent studies have suggested that neurodegeneration component of schizophrenia pathology some atypical antipsychotics appear to slow progressive morphological brain changes. In addition, the were reported superior therapeutic efficacy in treating low incidence extrapyramidal side effects (EPS) compared typical antipsychotics. However, mechanisms basis for differences their clinical still totally unknown. present study, we investigated whether paliperidone shows protective on SK-N-SH cells from cell toxicity induced by exposure glutamate. We examined drugs viability (measured MTT metabolism assay lactate dehydrogenase (LDH) activity assay), apoptosis rate, ROS levels gene expression phosphorylation Akt1 GSK3β. The results showed significantly increases LDH assays (p<0.05), contrast antipsychotic (haloperidol), which had little neuroprotective activity. Moreover, retarded glutamate-mediated promotion rate (p<0.05). also effectively reversed glutamate-induced decreases GSK3β (both p<0.05). Our demonstrated could protect damages via Akt1/GSK3β signaling pathway.
sci-hub.se 参考文章(28)
Patricia Gassó, Sergi Mas, Oriol Molina, Miquel Bernardo, Amalia Lafuente, Eduard Parellada, Neurotoxic/neuroprotective activity of haloperidol, risperidone and paliperidone in neuroblastoma cells. Progress in Neuro-psychopharmacology & Biological Psychiatry. ,vol. 36, pp. 71- 77 ,(2012) , 10.1016/J.PNPBP.2011.08.010
Jill A. Fowler, Tawny L. Bettinger, Tami R. Argo, Paliperidone extended-release tablets for the acute and maintenance treatment of schizophrenia. Clinical Therapeutics. ,vol. 30, pp. 231- 248 ,(2008) , 10.1016/J.CLINTHERA.2008.02.011
Burak Yulug, Aysegül Yildiz, Orkide Hüdaoglu, Erdinc Kilic, Ertugrul Cam, Wolf Rüdiger Schäbitz, Olanzapine attenuates brain damage after focal cerebral ischemia in vivo Brain Research Bulletin. ,vol. 71, pp. 296- 300 ,(2006) , 10.1016/J.BRAINRESBULL.2006.09.018
Eugene S. Kandel, Nissim Hay, The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB. Experimental Cell Research. ,vol. 253, pp. 210- 229 ,(1999) , 10.1006/EXCR.1999.4690
Qian Xiao, Chao Wang, Junchang Li, Qian Hou, Jinghua Li, Jing Ma, Wen Wang, Zongren Wang, Ginkgolide B protects hippocampal neurons from apoptosis induced by beta-amyloid 25-35 partly via up-regulation of brain-derived neurotrophic factor. European Journal of Pharmacology. ,vol. 647, pp. 48- 54 ,(2010) , 10.1016/J.EJPHAR.2010.08.002
Vuk Koprivica, Karen Regardie, Christina Wolff, Raymond Fernalld, Janelle Johnson Murphy, Junichi Kambayashi, Tetsuro Kikuchi, Shaun Jordan, Aripiprazole protects cortical neurons from glutamate toxicity European Journal of Pharmacology. ,vol. 651, pp. 73- 76 ,(2011) , 10.1016/J.EJPHAR.2010.10.064
Eve C. Johnstone, Christopher D. Frith, Validation of three dimensions of schizophrenic symptoms in a large unselected sample of patients. Psychological Medicine. ,vol. 26, pp. 669- 679 ,(1996) , 10.1017/S0033291700037685
Effat S Emamian, Diana Hall, Morris J Birnbaum, Maria Karayiorgou, Joseph A Gogos, Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nature Genetics. ,vol. 36, pp. 131- 137 ,(2004) , 10.1038/NG1296
S. Kurosawa, E. Hashimoto, W. Ukai, S. Toki, S. Saito, T. Saito, Olanzapine potentiates neuronal survival and neural stem cell differentiation: regulation of endoplasmic reticulum stress response proteins Journal of Neural Transmission. ,vol. 114, pp. 1121- 1128 ,(2007) , 10.1007/S00702-007-0747-Z
N. Kozlovsky, C. Shanon-Weickert, E. Tomaskovic-Crook, J. E. Kleinman, R. H. Belmaker, G. Agam, Reduced GSK-3β mRNA levels in postmortem dorsolateral prefrontal cortex of schizophrenic patients Journal of Neural Transmission. ,vol. 111, pp. 1583- 1592 ,(2004) , 10.1007/S00702-004-0166-3