Abstract
Senile plaques composed of β-amyloid protein (Aβ) and neurofibrillary tangles (NFTs) composed of intracellular hyper-phosphorylated tau are major causes of cognitive impairment and neuronal damage in Alzheimer disease (AD). Astragalin (AST), a naturally-occurring flavonoid compound, was reported to have neuroprotective effects in the brain, but its effects in AD remain unknown. Herein, the learning and memory deficits were alleviated and neuronal damage in the hippocampus were inhibited after the senescence-accelerated mouse prone 8 (SAMP8) mouse were given AST (5 mg/kg or 10 mg/kg) daily by gavage for 2 months. Furthermore, AST reduced Aβ1−40 and Aβ1−42 deposition, decreased β-carboxyl-terminal fragment (β-CTF) protein level and tau hyper-phosphorylation, but increased α-CTF protein level and glycogen synthase kinase-3beta (GSK-3β) phosphorylation in hippocampus of SAMP8 mice. Meanwhile, the effects of AST on AD were also explored in vitro by treating primary neurons with amyloid-β1–42 oligomers (Aβ1−42O). Consistently, AST also alleviated amyloid-β1–42 oligomers (Aβ1−42O)-induced neuronal damage, amyloid plaques, and tau phosphorylation in vitro model. Of note, estrogen receptor (ER)α and ERβ expression in the hippocampus of SAMP8 mice and Aβ1−42O-treated neurons was significantly decreased but their levels were increased by AST. Moreover, in vivo and in vitro experiments revealed that ER antagonist, Fulvestrant, reversed the effects caused by AST. Altogether, our investigation indicates that AST may ameliorate cognitive deficits and AD-type pathologies in SAMP8 mice and Aβ1−42O-treated neurons through upregulating ERα and ERβ expression. Our findings indicate the value of AST as a potential reagent for AD treatment.
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The data will be made available from the corresponding author on reasonable request.
Change history
02 November 2022
A Correction to this paper has been published: https://doi.org/10.1007/s11011-022-01089-z
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Funding
This research was supported by grants from the Surface Project of National Natural Science Foundation of China (82074288), the Youth Fund Project of National Natural Science Foundation of China (81403288), the Science Foundation for Youths of Heilongjiang Province (QC2015102), the Postdoctoral Science Foundation of China (2016M591565), the Project for Young Reserve Talents of Harbin Science and Technology Bureau (2016RAQXJ202) and the Postdoctoral Foundation of Heilongjiang Province (LBH-Z15207).
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Hong Liu and Jing Yang contributed to the study conception, design, and writing of the manuscript. Material preparation, data collection, and analysis were performed by Lili Zhong, Qiaomei Dai, and Yuwei Zhang. All authors read and approved the final manuscript.
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Liu, H., Zhong, L., Dai, Q. et al. Astragalin alleviates cognitive deficits and neuronal damage in SAMP8 mice through upregulating estrogen receptor expression. Metab Brain Dis 37, 3033–3046 (2022). https://doi.org/10.1007/s11011-022-01045-x
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DOI: https://doi.org/10.1007/s11011-022-01045-x