title: Melatonin attenuates hippocampal neuron apoptosis and oxidative stress during chronic intermittent hypoxia via up-regulating B-cell lymphoma-2 and down-regulating B-cell lymphoma-2-associated X protein.
abstract: OBJECTIVE
  To investigate the neuroprotective effect of melatonin against chronic intermittent hypoxia (CIH), the major pathophysiologic features of obstructive sleep apnea syndrome.
  
  
  METHODS
  This study was conducted between January 2011 and September 2012 in Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. Thirty 8-week Wistar rats were randomly divided into 3 groups (10 each): a control group, a vehicle-treated CIH group; and a melatonin-treated (10 mg/kg) CIH group. Rats were exposed to either intermittent hypoxia (IH) (oxygen concentration changing periodically from 21.78+/-0.65 to 6.57+/-0.57%), or air-air cycling at a rate of 30 cycles/hour, 8 hour/day for 4 weeks.
  
  
  RESULTS
  The CIH exposure led to a significant decrease in superoxide dismutase (SOD) activity and anti-apoptotic protein B-cell lymphoma-2 (BCL-2) expression in the hippocampus of CIH group rats compared with that of the control group and melatonin-treated CIH group. In contrast, hippocampal neuronal apoptosis increased significantly in parallel to an augment in 3,4-methylenedioxyamphetamine (MDA) content and pro-apoptotic protein Bcl-2-associated X protein (BAX) expression in CIH group than the other 2 groups. Melatonin administration abrogated the increase in MDA activity, as well as BAX expression, and restored SOD activity and BCL-2 expression to nearly their normal levels.
  
  
  CONCLUSIONS
  These results indicate melatonin can inhibit hippocampal neuron apoptosis following CIH by scavenging reactive oxygen species, up-regulating anti-apoptotic protein BCL-2 and down-regulating pro-apoptotic protein BAX, and thus, alleviate CIH-induced oxidative stress injury and produce neuroprotection effects.
authors.affiliation: Wuhan Brain Hospital, General Hospital of the Yangtze River Shipping, Wuhan, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Tan
authors.forename: Xueling
authors.initials: X
authors.lastname: Guo
authors.forename: Huiguo
authors.initials: H
authors.lastname: Liu
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015536:Down-Regulation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D015104:3,4-Methylenedioxyamphetamine; D013482:Superoxide Dismutase; D008550:Melatonin