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Hypoxic preconditioning ameliorates amyloid-β pathology and long-term cognitive decline in AβPP/PS1 transgenic mice

[ Vol. 17 , Issue. 7 ]

Author(s):

Jian Zhang, Ji Zhang, Xiao-Jia Li, Jun Xiao and Fang Ye*   Pages 626 - 634 ( 9 )

Abstract:


Background and Objective: Hypoxic Preconditioning (HPC) has been well established to trigger endogenous mechanisms of neuroprotection basing on models of hypoxic and ischemic diseases in the Central Nervous System (CNS). However, its effects against Alzheimer's Disease (AD) still lack substantial evidence and in-depth exploration. The present study aimed to investigate the impacts of HPC on AD-related memory decline and amyloid-β (Aβ) pathology in AβPP/PS1 transgenic mice.

Methods: Seven-week-old AβPP/PS1 transgenic mice were randomized into HPC and non-HPC groups. The HPC groups were treated with early and repetitive HPC for four weeks, while the non-HPC group was raised under normoxia condition. All the animals were then raised until the age of 28 weeks when Morris water maze tests were conducted to examine the animals’ spatial memory. Indicators for Aβ pathology (soluble Aβ levels and numbers of Aβ plaques) and the expression of relevant proteins were measured to explore potential mechanisms.

Results: The results showed that HPC ameliorated memory decline and Aβ pathology in AβPP/PS1 mice. The protein levels of Amyloid-β Precursor Protein (AβPP) and β-site APP Cleaving Enzyme 1 (BACE1) were reduced while that of Hypoxic inducible factor 1α (HIF-1α) was elevated in HPC groups.

Conclusion: HPC might be a promising strategy for AD intervention. Its potential protection might be realized via downregulating the expressions of AβPP and BACE1 and hence inhibiting Aβ pathology. Notably, HIF-1α might play a key role in mediating subsequent neuroadaptive changes following HPC.

Keywords:

Hypoxic preconditioning, Alzheimer`s disease, Aβ pathology, hypoxic inducible factor 1α, dementia, protective factors.

Affiliation:

Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu



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