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

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

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.

Keywords

Tyrosine Superoxide Schizophrenia Vanadium Nitrite 

Abbreviations

3-NT

3-Nitrotyrosine

Ach

Acetylcholine

AChE

Acetylcholine esterase

AD

Alzheimer’s disease

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

Notes

Acknowledgments

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
  • 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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