title: Apocynin attenuate spatial learning deficits and oxidative responses to intermittent hypoxia.
abstract: BACKGROUND
  The long-term intermittent hypoxia (LTIH) that characterizes sleep-disordered breathing impairs spatial learning and increases oxidative stress in rodents. We hypothesized that LTIH activated brain NADPH oxidase, which served as a critical source of superoxide in the oxidation injury, and that apocynin might attenuate LTIH-induced spatial learning deficits by reducing LTIH-induced NADPH oxidase expression.
  
  
  OBJECTIVE
  To investigate the effects of apocynin on spatial learning and oxidative responses to LTIH in rats.
  
  
  METHODS
  Forty healthy male Sprague-Dawley (SD) rats were randomly divided into four groups of 10 each: a LTIH group, an apocynin-treated LTIH group, a sham LTIH group and an apocynin-treated sham group. Spatial learning in each group was assessed with the Morris water maze test. RT-PCR and Western blot were used to examine mRNA and protein expression of NADPH oxidase subunit p47phox and p22phox in the hippocampus region. The level of MDA and SOD were detected by colorimetric method. The terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) method was used to display the apoptotic cells of the hippocampus tissue.
  
  
  RESULTS
  Apocynin treatment prevented LTIH-induced decreases in spatial learning during the Morris water maze as well as LTIH-induced decrease in SOD levels. In untreated animals, LTIH exposure was related to increase of MDA levels in comparison to sham LTIH animals, and apocynin-treated animal exposure to LTIH showed reduction in MDA levels. Increases in hippocampus NADPH oxidase subunit p47phox mRNA and protein expression were observed in LTIH-exposed animals; there was no statistical difference of p47phox mRNA and protein expression between LTIH group and apocynin treatment group. Treatment with apocynin significantly ameliorated cell apoptosis in LTIH-exposed animals.
  
  
  CONCLUSIONS
  These results indicate that apocynin attenuates LTIH-induced spatial learning deficits and mitigates LTIH-induced oxidative stress through multiple beneficial effects on oxidant pathways. NADPH oxidase up-expression is closely associated with oxidative processes in LTIH rats, and inhibition of NADPH oxidase activity may hopefully serve as a useful strategy for cognitive function impairment from chronic intermittent hypoxia.
authors.affiliation: Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease, Ministry of Health, Wuhan 430030, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Hui-guo
authors.forename: Liu
authors.initials: L
authors.lastname: Kui
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yan-ning
authors.forename: Xu
authors.initials: X
authors.lastname: Yong-jian
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D020287:In Situ Nick-End Labeling; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D019255:NADPH Oxidases / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000032:analysis
chemical_list: D000098:Acetophenones; D008315:Malondialdehyde; C056165:acetovanillone; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C515768:Cyba protein, rat; C060505:neutrophil cytosolic factor 1