title: Protective effect of carnosine on subcortical ischemic vascular dementia in mice.
abstract: OBJECTIVE
  Recently, we found carnosine protects against N-Methyl-D-Aspartate (NMDA) induced excitotoxicity through a histaminergic pathway. The aim of this study was to determine whether the carnosine-histidine-histamine pathway also played a protective role in subcortical ischemic vascular dementia (SIVD).
  
  
  METHODS
  Adult male mice (C57BL/6 strain) were subjected to right unilateral common carotid arteries occlusion (rUCCAO) and treated with carnosine or histidine. Object recognition test, passive avoidance task, Morris water maze, and immunohistochemical analyses were performed after rUCCAO.
  
  
  RESULTS
  We found that carnosine (200, 500 mg/kg) ameliorated white matter lesion and cognitive impairment evaluated by object recognition test, passive avoidance task, and Morris water maze test after rUCCAO in both wide-type mice and histidine decarboxylase knockout mice, which are lack of endogenous histamine. However, administration of histidine did not show the same effect. The myelin basic protein in the corpus callosum decreased obviously at day 37 after rUCCAO, which was largely reversed by carnosine (200, 500 mg/kg). Carnosine (200, 500 mg/kg) suppressed the activation of microglia and astrocyte as attenuating the elevation of glial fibrillary acidic protein (GFAP) and Iba-1 fluorescent intensity. Moreover, carnosine (200, 500 mg/kg) significantly attenuated the increase in reactive oxygen species generation after rUCCAO.
  
  
  CONCLUSIONS
  These data suggest that the neuroprotective effect of carnosine on rUCCAO in mice is not dependent on the histaminergic pathway, but may be due to a suppression of reactive oxygen species generation, glia activation, and myelin degeneration.
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Basic Medical Sciences, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Jia-Yan
authors.initials: JY
authors.lastname: Xiong
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hou
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Yan
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.forename: Shang-Wei
authors.initials: SW
authors.lastname: Huang
authors.forename: Le
authors.initials: L
authors.lastname: Jin
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002336:Carnosine / Q000494:pharmacology*; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000378:metabolism*; D006639:Histidine / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects; D004676:Myelin Basic Protein / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D004676:Myelin Basic Protein; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D006639:Histidine; D006632:Histamine; D002336:Carnosine; D006640:Histidine Decarboxylase