Prevention of neurodegenerative damage to the brain in rats in experimental Alzheimer's disease by adaptation to hypoxia.
We report here studies addressing the possibility of preventing neurodegenerative changes in the brain using adaptation to periodic hypoxia in rats with experimental Alzheimer's disease induced by administration of the neurotoxic peptide fragment of beta-amyloid (Ab) into the basal magnocellular nucleus. Adaptation to periodic hypoxia was performed in a barochamber (4000 m, 4 h per day, 14 days). The following results were obtained 15 days after administration of Ab. 1. Adaptation to periodic hypoxia significantly blocked Ab-induced memory degradation in rats, as assessed by testing a conditioned passive avoidance reflex. 2. Adaptation to periodic hypoxia significantly restricted increases in oxidative stress, measured spectrophotometrically in the hippocampus in terms of the content of thiobarbituric acid-reactive secondary lipid peroxidation products. 3. Adaptation to periodic hypoxia completely prevented the overproduction of NO in the brains of rats with experimental Alzheimer's disease, as measured in terms of increases in tissue levels of stable NO metabolites, i.e., nitrites and nitrates. 4. The cerebral cortex of rats given Ab injections after adaptation to periodic hypoxia did not contain neurons with pathomorphological changes or dead neurons (Nissl staining), which were typical in animals with experimental Alzheimer's disease. Thus, adaptation to periodic hypoxia effectively prevented oxidative and nitrosative stress, protecting against neurodegenerative changes and protecting cognitive functions in experimental Alzheimer's disease.
Manukhina
E B
EB
State Research Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, 8 Baltiiskaya St., 125315, Moscow, Russia. manukh@orc.ru
Goryacheva
A V
AV
Barskov
I V
IV
Viktorov
I V
IV
Guseva
A A
AA
Pshennikova
M G
MG
Khomenko
I P
IP
Mashina
S Yu
SY
Pokidyshev
D A
DA
Malyshev
I Yu
IY
D000222:Adaptation, Physiological; D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000860:Hypoxia; D015227:Lipid Peroxidation; D008568:Memory / Q000187:drug effects; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control*; D009474:Neurons / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D009573:Nitrites; D010446:Peptide Fragments; D009569:Nitric Oxide