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The combination of acyclovir and dexamethasone protects against Alzheimer’s disease-related cognitive impairments in mice

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Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease. However, effective drugs for this disease have not yet been developed. The analysis of big data indicated that childhood herpes virus infection may be associated with the incidence of AD, suggesting that anti-herpetic drugs, such as acyclovir, may have preventive and suppressive effects in AD therapy. Moreover, short-term use of dexamethasone (DXMT), a clinical used synthetic corticosteroid, could effectively inhibit AD-related neuroinflammation. In this study, we have found that the combination of acyclovir and DXMT, but not acyclovir or DXMT alone, could protect against AD causing β-amyloid (Aβ) oligomer-induced spatial cognitive impairments. Moreover, acyclovir and DXMT could prevent Aβ oligomer-induced over-activation of microglia and astrocytes, and over-expression of pro-inflammatory cytokines, indicating that anti-AD effects of drug combination might be at least partially via neuroinflammation inhibition and immunomodulation. Furthermore, Aβ oligomer-induced decrease of PSD-95 and increase of pTau expression was prevented by the combination of acyclovir and DXMT, suggesting the involvement of synaptic protective effects of the drug combination. Taken together, our studies indicated that the combination of acyclovir and DXMT might be an alternative therapy for the treatment of AD.

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Abbreviations

Aβ:

β-amyloid

AD:

Alzheimer’s disease

DXMT:

Dexamethasone

TNF-α:

Tumor necrosis factor-α

HFIP:

1,1,1,3,3,3-hexafluoro-2-propanol

ICR:

Institute of Cancer Research

IL-6:

Interleukin-6

i.g. :

Intragastric

i.p.:

Intraperitoneal

OD:

Optical density

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Acknowledgments

This research was funded by the National Natural Science Foundation of China (81870853), Ningbo Sci and Tech Project for Common Wealth (2017C50042), Zhejiang Key Laboratory of Pathophysiology (201804), Ningbo Municipal Innovation Team of Life Science and Health (2015C110026), LiDakSum Marine Biopharmaceutical Development Fund, and the K. C. Wong Magna Fund in Ningbo University.

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Authors and Affiliations

  1. Translational Medicine Center of Pain, Emotion and Cognition, Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, 315211, China

    Zhang Hui, Yuan Zhijun, Yan Yushan, Chen Liping, Zhou Yiying, Zhang Difan & Cui Wei

  2. PlantaRx Limited, 85 Prince Edward Road West, Hong Kong, SAR, China

    Choi Tony Chunglit

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  1. Zhang Hui
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  2. Yuan Zhijun
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  3. Yan Yushan
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  4. Chen Liping
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  5. Zhou Yiying
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  7. Choi Tony Chunglit
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Correspondence to Choi Tony Chunglit or Cui Wei.

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Hui, Z., Zhijun, Y., Yushan, Y. et al. The combination of acyclovir and dexamethasone protects against Alzheimer’s disease-related cognitive impairments in mice. Psychopharmacology 237, 1851–1860 (2020). https://doi.org/10.1007/s00213-020-05503-1

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  • DOI: https://doi.org/10.1007/s00213-020-05503-1

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