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Protective Effect of Hydroxysafflor Yellow A against Chronic Mild Stress-induced Memory Impairments by Suppressing Tau Phosphorylation in Mice

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Summary

Chronic stress plays a critical role in the etiology of sporadic Alzheimer’s disease (AD). However, there are currently no effective drugs that can target chronic stress to prevent AD. In this study, we explored the neuroprotective effect of hydroxysafflor yellow A (HSYA) against chronic mild stress (CMS)-induced memory impairments in mice and the underlying mechanism. The Morris water maze test showed that HSYA significantly reduced CMS-induced learning and memory impairments in mice. HSYA increased the expression of brain-derived neurotrophic factor (BDNF) and activated downstream tropomyosin-related kinase B (TrkB) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt)/mammalian target of rapamycin (mTOR) signaling. HSYA decreased the expression of regulator of calcineurin 1-1L (RCAN1-1L) that could promote the activity of glycogen synthase kinase-3β (GSK-3β). HSYA also attenuated tau phosphorylation by inhibiting the activity of GSK-3β and cyclin-dependent kinase-5 (Cdk5). Our data indicated that HSYA has protective effects against CMS-induced BDNF downregulation, tau phosphorylation and memory impairments. HSYA may be a promising therapeutic candidate for AD by targeting chronic stress.

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Authors and Affiliations

  1. Department of Neurology, The First Hospital of Lanzhou University, Lanzhou, 730000, China

    Ying Wang, Qiang Wang, Jun Chen, Li-he Yao, Ni Tang & Zhen-xiu Jiang

  2. Institute of Pathophysiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China

    Yu Luo

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  1. Ying Wang
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  2. Qiang Wang
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  3. Jun Chen
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Correspondence to Yu Luo.

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The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.

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This work was supported by the Fundamental Research Funds for the Central Universities (No. lzujbky-2016-70) and the Natural Science Foundation of Gansu Province (No. 1506RJZA235).

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Wang, Y., Wang, Q., Chen, J. et al. Protective Effect of Hydroxysafflor Yellow A against Chronic Mild Stress-induced Memory Impairments by Suppressing Tau Phosphorylation in Mice. CURR MED SCI 41, 555–564 (2021). https://doi.org/10.1007/s11596-021-2369-3

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