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Cornel iridoid glycoside ameliorates cognitive deficits in APP/PS1/tau triple transgenic mice by attenuating amyloid‐beta, tau, and neurotrophic dysfunction
Author(s) -
Yang Cuicui,
Zhang Lan
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045667
Subject(s) - morris water navigation task , hippocampus , amyloid precursor protein , chemistry , tau protein , creb , endocrinology , medicine , neurotrophic factors , genetically modified mouse , amyloid beta , amyloid (mycology) , transgene , pharmacology , alzheimer's disease , biochemistry , peptide , receptor , transcription factor , disease , gene , inorganic chemistry
Background Targeting proteinopathies is involved in the protective effects of pharmacologic agents to treat Alzheimer’s disease (AD). Cornel iridoid glycoside (CIG) are the effective component from Cornus officinalis. The aim of the present research was to explore the potential effects of CIG on β‐amyloid (Aβ) and tau pathology and its underlying mechanisms in APP/PS1/Tau triple transgenic (3×Tg) mice. Method We intragastrically administered 16‐month‐old 3×Tg mice with CIG (100 and 200 mg/kg) for 2 months. Morris water maze and object recognition tests were used to detect learning and memory abilities. Thioflavin‐S staining and immunohistochemistry were used to detect amyloid plaques and Aβ40/42. Western blotting assay was performed to determine the expression of related proteins in the cerebral cortex and hippocampus of mice. Result The results showed that CIG treatment improved learning and memory impairment in 3×Tg mice. CIG decreased amyloid plaque deposition, Aβ40/42 and the expression of full‐length amyloid precursor protein; and increased the levels of ADAM‐10 (a‐secretase), neprilysin (NEP) and insulin degrading enzyme (IDE) in the brain of 3×Tg mice. Moreover, CIG reduced tau hyperphosphorylation, and elevated phosphorylation level of GSK‐3β at Ser9 and methylation of PP2A catalytic subunit C in the model mice. 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. Conclusion 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.