Cornel iridoid glycoside ameliorates cognitive deficits in APP/PS1/tau triple transgenic mice by attenuating amyloid-beta, tau hyperphosphorylation and neurotrophic dysfunction
Cuicui Yang, Xunjie Bao, Li Zhang, Yali Li, Lin Li, Lan Zhang
Abstract
BACKGROUND: . The present study aimed to determine the effects of CIG on β-amyloid (Aβ) and tau pathology and the underlying mechanisms in APP/PS1/tau triple transgenic (3×Tg) model mice. METHODS: We intragastrically administered 16-month-old 3×Tg mice with CIG (100 and 200 mg/kg) daily for two months. Learning and memory abilities were determined using the Morris water maze (MWM) and object recognition tests (ORT). Amyloid plaques and Aβ40/42 and the expression of related proteins in the cerebral cortex and hippocampus of mice was determined by western blotting. RESULTS: CIG improved learning and memory impairment in 3×Tg model mice, decreased amyloid plaque deposition, Aβ40/42 and the expression of full-length amyloid precursor protein, and increased levels of ADAM-10 (α-secretase), neprilysin (NEP), and insulin degrading enzyme (IDE) in the brains of the model mice. CIG also reduced tau hyperphosphorylation, and elevated phosphorylation level of GSK-3β at Ser9 and methylation of PP2A catalytic subunit C in the model mice. Moreover, CIG increased the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-responsive element binding protein (p-CREB) in the brain of 3×Tg mice. CONCLUSIONS: CIG ameliorated learning and memory deficit via reducing Aβ content and, tau hyperphosphorylation and increasing neurotrophic factors in the brain of 3×Tg mice. These results suggest that CIG may be beneficial for AD therapy.