1. Rutaecarpine Ameliorated High Sucrose-Induced Alzheimer's Disease Like Pathological and Cognitive Impairments in Mice.
- Author
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Zhao, Bin, Wang, Yi, Liu, Rui, Jia, Xiao-Li, Hu, Nan, An, Xing-Wei, Zheng, Chen-Guang, Chen, Chong, Sun, Hong-Tao, Chen, Feng, Wang, Jing-Jing, and Li, Xiao-Hong
- Subjects
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SUCROSE , *ALZHEIMER'S disease , *ALKALOIDS , *HETEROCYCLIC compounds , *ANIMAL experimentation , *ANIMALS , *MICE , *PHOSPHORYLATION - Abstract
High sucrose can induce tau hyperphosphorylation and cognitive dysfunction/memory impairment as observed in Alzheimer's disease (AD). Rutaecarpine, a specific (transient receptor potential vanilloid 1 [TRPV1]) agonist, is neuroprotective against high sucrose diet-induced impairment, but detailed mechanisms are still elusive. In this study, we investigated whether rutaecarpine mitigates high sucrose diet-induced pathological alterations and cognitive in AD-like mice. Mice were administered fodder containing 0.01% rutaecarpine and 20% sucrose solution. Our results showed that rutaecarpine significantly attenuated high sucrose diet-induced spatial memory impairment and enhanced synaptic plasticity; rutaecarpine prevented high sucrose diet-induced tau hyperphosphorylation by decreasing glycogen synthase kinase-3β (GSK-3β) activity; activation of GSK-3β reversed the protective effect of rutaecarpine on learning and memory deficits, synaptic plasticity, and tau hyperphosphorylation induced by high-glucose diet significantly, suggesting that GSK-3β activation is required for high glucose-induced tau hyperphosphorylation. These results demonstrated that rutaecarpine can mitigate high sucrose diet-induced hyperphosphorylation of AD-associated tau protein and cognitive impairment by inhibiting GSK-3β, which supported that dietary rutaecarpine might have a promising use for therapeutic intervention of AD. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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