Protective effect of carnosine on subcortical ischemic vascular dementia in mice.

Abstract

AIMS:

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.

CONCLUSION:

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: Jing Ma, Jia-Yan Xiong, Wei-Wei Hou, Hai-Jing Yan, Yun Sun, Shang-Wei Huang, Le Jin, Ye Wang, Wei-Wei Hu, Zhong Chen
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 18 Issue 9 Pg. 745-53 (Sep 2012) ISSN: 1755-5949 [Electronic] England
• PMID: 22943141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

• Myelin Basic Protein
• Neuroprotective Agents
• Reactive Oxygen Species
• Histidine
• Histamine
• Carnosine
• Histidine Decarboxylase

Topics

• Animals
• Avoidance Learning (drug effects)
• Carnosine (pharmacology)
• Corpus Callosum (drug effects, metabolism)
• Dementia, Vascular (drug therapy, metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Histamine (metabolism)
• Histidine (pharmacology)
• Histidine Decarboxylase (genetics, metabolism)
• Male
• Maze Learning (drug effects)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microglia (drug effects)
• Myelin Basic Protein (metabolism)
• Neuroprotective Agents (pharmacology)
• Reactive Oxygen Species (metabolism)
• Recognition, Psychology (drug effects)