Protective Effects of Adaptation to Hypoxia in Experimental Alzheimer’s Disease

  • Eugenia B. ManukhinaEmail author
  • Anna V. Goryacheva
  • Maya G. Pshennikova
  • Igor Yu. Malyshev
  • Robert T. Mallet
  • H. Fred Downey


Alzheimer’s disease (AD) is characterized by formation of amyloid plaques, intracellular neurofibrillary tangles, and cell death in the brain, resulting in progressive loss of memory and cognitive ability. Efficacy of drugs currently used for prevention and treatment of AD is limited by the fact that each drug influences only a single step of the pathogenesis in AD, and the drugs affect both damaged and normal cells. This is why major attention is now paid to nonpharmacological means that may enhance the adaptive capacity and mobilize the self-defense systems of the body. This chapter focuses on protective effects of adaptation to intermittent hypobaric hypoxia on the memory, brain neurons, and cerebral blood vessels in rats with experimental AD induced by intracerebral injections of beta-amyloid (Aβ) and mechanisms of these protective effects. Special attention is paid to intermittent hypobaric hypoxia’s ability to limit early stages in AD pathogenesis, such as nitrosative and oxidative stress in brain tissue. Presented data show that adaptation to hypoxia may be a promising approach to prevention and treatment of AD.


Nitric Oxide Mitochondrial Permeability Transition Pore Intermittent Hypoxia Mitochondrial Permeability Transition Pore Hypobaric Hypoxia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.







Acetylcholine esterase


Alzheimer’s disease



α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid


Dinitrosyl iron complex


Hypoxia-inducible factor-1


Hypoxic response element


Heat shock protein


Local cerebral blood flow




Long-term potentiation


Mitochondrial permeability transition pore




N-Methyl d-aspartate




Nitric oxide


NO synthase


Endothelial NO synthase


Inducible NO synthase


Neuronal NO synthase


Protein kinase C


Reactive oxygen species


Thiobarbituric acid-reactive substances


Tumor necrosis factor α


Vascular endothelial growth factor



This work was supported by the Russian Foundation for Basic Research (grant 07–04–00650).


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Copyright information

© Springer-Verlag London 2012

Authors and Affiliations

  • Eugenia B. Manukhina
    • 1
    • 3
    Email author
  • Anna V. Goryacheva
    • 1
  • Maya G. Pshennikova
    • 1
  • Igor Yu. Malyshev
    • 3
    • 4
  • Robert T. Mallet
    • 2
  • H. Fred Downey
    • 2
  1. 1.Laboratory for Regulatory Mechanisms of AdaptationInstitute of General Pathology and PathophysiologyMoscowRussia
  2. 2.Department of Integrative PhysiologyUniversity of North Texas Health Science CenterFort WorthUSA
  3. 3.Laboratory of Stress and AdaptationInstitute of General Pathology and PathophysiologyMoscowRussia
  4. 4.Department of PathophysiologyMoscow State University of Medicine and DentistryMoscowRussia

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