title: Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2.
abstract: Homocysteine, a risk factor for Alzheimer's disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2.
  
  
  
  The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot.
  
  
  
  The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats.
  
  
  
  Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2.
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience, Medical College.|University of South China, Hengyang, Hunan, PR China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, Hunan, PR China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Wei
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital.
authors.forename: Man-Hong
authors.initials: MH
authors.lastname: Li
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, University of South China, Hengyang, Hunan, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Neuroscience, Medical College.
authors.forename: Hong-Feng
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital.|Institute of Neuroscience, Medical College.|University of South China, Hengyang, Hunan, PR China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, Hunan, PR China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tang
mesh_terms: D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D064426:Gasotransmitters / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006710:Homocysteine / Q000633:toxicity; D006862:Hydrogen Sulfide / Q000627:therapeutic use*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011804:Quinolines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D065854:Spatial Navigation / Q000187:drug effects; D045162:Thiazolidinediones / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C575035:(Z)2-(5-(4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetic acid; D000447:Aldehydes; D064426:Gasotransmitters; D011804:Quinolines; D045162:Thiazolidinediones; D006710:Homocysteine; C047117:bicinchoninic acid; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D006862:Hydrogen Sulfide
keywords: ALDH2; GSH; cognitive dysfunction; homocysteine; hydrogen sulfide; reactive aldehydes