title: Quetiapine Ameliorates Schizophrenia-Like Behaviors and Protects Myelin Integrity in Cuprizone Intoxicated Mice: The Involvement of Notch Signaling Pathway.
abstract: BACKGROUND
  White matter disturbances and myelin impairment are key features of schizophrenia. The antipsychotic drug quetiapine can promote the maturation of oligodendrocytes, but the molecular mechanisms remain largely unknown.
  
  
  METHODS
  The schizophrenia-like behaviors, degrees of demyelination, and levels of Notch signaling molecules in forebrains of adult male C57BL/6 mice were examined after fed with cuprizone (0.2% wt/wt) in the presence or absence of 10mg/kg/d quetiapine for 6 weeks. These parameters were also observed after the transcranial injection of Notch signaling inhibitor MW167 (1mM) daily during the last week of the treatment period.
  
  
  RESULTS
  Quetiapine ameliorated the schizophrenia-like behaviors and decreased expression of myelin basic protein and inhibition of Notch signaling molecules, such as Notch1, Hes1, and Hes5, in the forebrain that induced by cuprizone. These beneficial effects of quetiapine were abolished by MW167.
  
  
  CONCLUSIONS
  The antipsychotic and myelin protective effects of quetiapine are mediated by Notch signaling in a mouse model of cuprizone-induced demyelination associated with schizophrenia-like behaviors. The Notch pathway might therefore be a novel target for the development of antipsychotic drugs.
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China (Drs Wang, Liu, Zhang, Xue, Wu, Chen, Y. Peng, Z.-w. Peng, and Tan); Air Force General Hospital of PLA, Beijing, China (Dr Y. Peng); Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an, China (Dr Z-w. Peng).
authors.forename: Hua-ning
authors.initials: HN
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China (Drs Wang, Liu, Zhang, Xue, Wu, Chen, Y. Peng, Z.-w. Peng, and Tan); Air Force General Hospital of PLA, Beijing, China (Dr Y. Peng); Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an, China (Dr Z-w. Peng).
authors.forename: Gao-hua
authors.initials: GH
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China (Drs Wang, Liu, Zhang, Xue, Wu, Chen, Y. Peng, Z.-w. Peng, and Tan); Air Force General Hospital of PLA, Beijing, China (Dr Y. Peng); Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an, China (Dr Z-w. Peng).
authors.forename: Rui-guo
authors.initials: RG
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China (Drs Wang, Liu, Zhang, Xue, Wu, Chen, Y. Peng, Z.-w. Peng, and Tan); Air Force General Hospital of PLA, Beijing, China (Dr Y. Peng); Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an, China (Dr Z-w. Peng).
authors.forename: Fen
authors.initials: F
authors.lastname: Xue
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China (Drs Wang, Liu, Zhang, Xue, Wu, Chen, Y. Peng, Z.-w. Peng, and Tan); Air Force General Hospital of PLA, Beijing, China (Dr Y. Peng); Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an, China (Dr Z-w. Peng).
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China (Drs Wang, Liu, Zhang, Xue, Wu, Chen, Y. Peng, Z.-w. Peng, and Tan); Air Force General Hospital of PLA, Beijing, China (Dr Y. Peng); Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an, China (Dr Z-w. Peng).
authors.forename: Yun-chun
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China (Drs Wang, Liu, Zhang, Xue, Wu, Chen, Y. Peng, Z.-w. Peng, and Tan); Air Force General Hospital of PLA, Beijing, China (Dr Y. Peng); Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an, China (Dr Z-w. Peng).
authors.forename: Ye
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China (Drs Wang, Liu, Zhang, Xue, Wu, Chen, Y. Peng, Z.-w. Peng, and Tan); Air Force General Hospital of PLA, Beijing, China (Dr Y. Peng); Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an, China (Dr Z-w. Peng). pengzhengwu1446@163.com tanqingr@fmmu.edu.cn.
authors.forename: Zheng-wu
authors.initials: ZW
authors.lastname: Peng
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China (Drs Wang, Liu, Zhang, Xue, Wu, Chen, Y. Peng, Z.-w. Peng, and Tan); Air Force General Hospital of PLA, Beijing, China (Dr Y. Peng); Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an, China (Dr Z-w. Peng). pengzhengwu1446@163.com tanqingr@fmmu.edu.cn.
authors.forename: Qing-rong
authors.initials: QR
authors.lastname: Tan
mesh_terms: D000818:Animals; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010455:Peptides / Q000494:pharmacology; D000069348:Quetiapine Fumarate / Q000008:administration & dosage*; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: C432344:MW167; D018696:Neuroprotective Agents; D010455:Peptides; D051880:Receptors, Notch; D000069348:Quetiapine Fumarate; D003471:Cuprizone
keywords: Notch; myelination; quetiapine; schizophrenia