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Inhibition of extracellular signal-regulated kinase activity improves cognitive function in Tg2576 mice.
MedLine Citation:
PMID:  23013130     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Deposition of β-amyloid (Aβ) peptide is a defining pathological hallmark of Alzheimer's disease (AD) and is involved in memory impairment. Evidence suggests that activation of an extracellular signal-regulated kinase (ERK) pathway is related to Aβ accumulation. Thus, the aim of the present study was to investigate the effects of an ERK inhibitor (U0126) on amyloidogenesis and cognitive function in Tg2576 mice. Tg2576 mice were injected with U0126 (20 mg/kg, i.p.) or vehicle (1% dimethyl sulphoxide in sterile saline) once a day for 7 days and then cognitive function was assessed by the Morris water maze test and passive avoidance test. In addition, immunostaining, western blot analysis, ELISA and enzyme activity assays were used to examine the degree of Aβ deposition in the brains of Tg2576 mice. Our results showed that U0126 attenuated memory impairment and inhibited Aβ deposition in the brains of Tg2576 mice. Further experiments revealed that the inhibition of Aβ deposition by U0126 was due to a reduction in β-secretase and amyloid precursor protein expression in the brains of U0126-treated Tg2576 mice. These results suggest that the ERK pathway is associated with Aβ accumulation and consequent memory dysfunction in Tg2576 mice and that inhibition of the ERK pathway may be an appropriate intervention in the treatment of AD.
Authors:
Peng Jin; Dong-Young Choi; Jin Tae Hong
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  39     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  852-7     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.
Affiliation:
College of Pharmacy, Chungbuk National University, Cheongju, Korea; Medical Research Centre, Chungbuk National University, Cheongju, Korea.
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