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

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Intermittent Hypoxia and Human Diseases

Abstract

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.

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Abbreviations

3-NT:

3-Nitrotyrosine

Ach:

Acetylcholine

AChE:

Acetylcholine esterase

AD:

Alzheimer’s disease

Aβ:

β-Amyloid

AMPA:

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

DNIC:

Dinitrosyl iron complex

HIF-1:

Hypoxia-inducible factor-1

HRE:

Hypoxic response element

HSP:

Heat shock protein

LCBF:

Local cerebral blood flow

IL:

Interleukin

LTP:

Long-term potentiation

MPTP:

Mitochondrial permeability transition pore

NAC:

N-Acetylcysteine

NMDA:

N-Methyl d-aspartate

L-NNA:

Nω-Nitro-L-arginine

NO:

Nitric oxide

NOS:

NO synthase

eNOS:

Endothelial NO synthase

iNOS:

Inducible NO synthase

nNOS:

Neuronal NO synthase

PKC:

Protein kinase C

ROS:

Reactive oxygen species

TBARS:

Thiobarbituric acid-reactive substances

TNFα:

Tumor necrosis factor α

VEGF:

Vascular endothelial growth factor

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Acknowledgments

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

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Authors and Affiliations

  1. Laboratory for Regulatory Mechanisms of Adaptation, Institute of General Pathology and Pathophysiology, Moscow, Russia

    Eugenia B. Manukhina, Anna V. Goryacheva & Maya G. Pshennikova

  2. Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX, USA

    Robert T. Mallet & H. Fred Downey

  3. Laboratory of Stress and Adaptation, Institute of General Pathology and Pathophysiology, Moscow, Russia

    Eugenia B. Manukhina & Igor Yu. Malyshev

  4. Department of Pathophysiology, Moscow State University of Medicine and Dentistry, Moscow, Russia

    Igor Yu. Malyshev

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  1. Eugenia B. Manukhina
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  2. Anna V. Goryacheva
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  3. Maya G. Pshennikova
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  4. Igor Yu. Malyshev
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  5. Robert T. Mallet
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  6. H. Fred Downey
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Correspondence to Eugenia B. Manukhina .

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  1. , Division of Cardiology, Virginia Commonwealth University, Richmond, 23298, Virginia, USA

    Lei Xi

  2. Bogomoletz Institute of Physiology, Kiev, 01601, Ukraine

    Tatiana V. Serebrovskaya

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Manukhina, E.B., Goryacheva, A.V., Pshennikova, M.G., Malyshev, I.Y., Mallet, R.T., Downey, H.F. (2012). Protective Effects of Adaptation to Hypoxia in Experimental Alzheimer’s Disease. In: Xi, L., Serebrovskaya, T. (eds) Intermittent Hypoxia and Human Diseases. Springer, London. https://doi.org/10.1007/978-1-4471-2906-6_13

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