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Inhibition of extracellular signal‐regulated kinase activity improves cognitive function in T g2576 mice
Author(s) -
Jin Peng,
Choi DongYoung,
Hong Jin Tae
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2012.12000.x
Subject(s) - mapk/erk pathway , morris water navigation task , extracellular , kinase , western blot , immunostaining , amyloid precursor protein , protein kinase a , signal transduction , chemistry , endocrinology , hippocampus , alzheimer's disease , medicine , pharmacology , biochemistry , immunohistochemistry , disease , gene
Summary Deposition of β ‐amyloid ( A β ) peptide is a defining pathological hallmark of A lzheimer's disease ( AD ) and is involved in memory impairment. Evidence suggests that activation of an extracellular signal‐regulated kinase ( ERK ) pathway is related to A β accumulation. Thus, the aim of the present study was to investigate the effects of an ERK inhibitor ( U 0126) on amyloidogenesis and cognitive function in T g2576 mice. T g2576 mice were injected with U 0126 (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 A β deposition in the brains of T g2576 mice. Our results showed that U 0126 attenuated memory impairment and inhibited A β deposition in the brains of T g2576 mice. Further experiments revealed that the inhibition of A β deposition by U 0126 was due to a reduction in β ‐secretase and amyloid precursor protein expression in the brains of U 0126‐treated T g2576 mice. These results suggest that the ERK pathway is associated with A β 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 .