title: Effects of melatonin on the nitric oxide system and protein nitration in the hypobaric hypoxic rat hippocampus.
abstract: BACKGROUND
  It is well documented that the nitric oxide (NO) might be directly involved in brain response to hypobaric hypoxia, and could contribute to memory deficiencies. Recent studies have shown that melatonin could attenuate hypoxia or ischemia-induced nerve injuries by decreasing the production of free radicals. The present study, using immunohistochemical and immunoblot methods, aimed to explore whether melatonin treatment may affect the expression of nitric oxide system and protein nitration, and provide neuroprotection in the rat hippocampus injured by hypobaric hypoxia. Prior to hypoxic treatment, adult rats were pretreated with melatonin (100 mg/kg, i.p.) before they were exposed to the altitude chamber with 48 Torr of the partial oxygen concentration (pO2) for 7 h to mimic the ambience of being at 9000 m in height. They were then sacrificed after 0 h, 1, and 3 days of reoxygenation.
  
  
  RESULTS
  The results obtained from the immunohistochemical and immunoblotting analyses showed that the expressions of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), nitrotyrosine (Ntyr) and Caspase 3 in the hypoxic hippocampus were increased from 0 h to 3 days of reoxygenation. Interestingly, the hypoxia-induced increase of nNOS, eNOS, iNOS, Ntyr and Caspase 3 protein expression was significantly depressed in the hypoxic rats treated with melatonin.
  
  
  CONCLUSIONS
  Activation of the nitric oxide system and protein nitration constitutes a hippocampal response to hypobaric hypoxia and administration of melatonin could provide new therapeutic avenues to prevent and/or treat the symptoms produced by hypobaric hypoxia.
authors.affiliation: Department of Psychiatry, China Medical University Hospital, No. 91 Hsueh-Shih Road, Taichung, Taiwan. chihchiahuang@yahoo.com.tw.|Institute of Clinical Medical Science, China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan. chihchiahuang@yahoo.com.tw.|Department of Psychiatry, China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan. chihchiahuang@yahoo.com.tw.
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Institute of Basic Medical Science, China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan. cutemeizi@yahoo.com.tw.
authors.forename: Chia-Jou
authors.initials: CJ
authors.lastname: Lai
authors.affiliation: Department of Anatomy, China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan. mhtsai@mail.cmu.edu.tw.
authors.forename: Mang-Hung
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Department of Nursing, Ching-Kuo Institute of Management and Health, 336, Fu-Hsin Road, Keelung, Taiwan. r89446007@ntu.edu.tw.
authors.forename: Ya-Chieh
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Institute of Basic Medical Science, China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan. felix731205@yahoo.com.tw.
authors.forename: Kuang-Ti
authors.initials: KT
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine for Post Baccalaureate, I Shou University, No. 1, Sec. 1, Syuecheng Road, Dashu District, Kaohsiung, Taiwan. mjjou@isu.edu.tw.
authors.forename: Ming-Jia
authors.initials: MJ
authors.lastname: Jou
authors.affiliation: Department of Anatomy, China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan. p520142001@hotmail.com.
authors.forename: Pin-I
authors.initials: PI
authors.lastname: Fu
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, Taiwan. chw0204@tmu.edu.tw.
authors.forename: Ching-Hsiang
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Anatomy, China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan. ihwei@mail.cmu.edu.tw.
authors.forename: I-Hua
authors.initials: IH
authors.lastname: Wei
mesh_terms: D000532:Altitude Sickness / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D000860:Hypoxia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D053148:Caspase 3; D008550:Melatonin