title: Role of nitric oxide in prevention of cognitive disorders in neurodegenerative brain injuries in rats.
abstract: NO synthesis disturbances play an important role in the development of neurodegenerative damage in Alzheimer disease. We previously showed that adaptation to intermittent hypobaric hypoxia prevents cognitive disturbances in rats with experimental Alzheimer disease. Here we evaluated the role of NO in cognitive disorders and development of adaptive protection during experimental Alzheimer disease. Adaptation to hypoxia in rats was performed in a hypobaric pressure chamber at a simulated altitude of 4000 m (4 h per day for 14 days). Alzheimer disease was simulated by bilateral injections of a toxic fragment of beta-amyloid (25-35) into n. basalis magnocellularis. For evaluation of the role of NO in the development and prevention of memory disorders, the rats received intraperitoneally either NO-synthase inhibitor N omega-nitro-L-arginin (L-NNA, 20 mg/kg, every other day for 14 days) or NO-donor dinitrosyl iron complex (200 microg/kg daily for 14 days). NO-synthase inhibitor potentiated the damaging effect of beta-amyloid, abolished the protective effect of adaptation to hypoxia, and produced memory disorders in rats similar to those observed during experimental Alzheimer disease. In contrast, the increase in NO level in the body provided by injections of the NO-donor produced a protective effect against memory disorders caused by beta-amyloid similar to that induced by adaptation to hypoxia. We concluded that reduced NO production in the organism plays an important role in the development of cognitive disorders produced by injections of beta-amyloid, while prevention of NO deficit by administration of NO-donors or non-pharmacological stimulation of NO synthesis can provide a protective effect in experimental Alzheimer disease.
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: E B
authors.initials: EB
authors.lastname: Manukhina
authors.forename: M G
authors.initials: MG
authors.lastname: Pshennikova
authors.forename: A V
authors.initials: AV
authors.lastname: Goryacheva
authors.forename: I P
authors.initials: IP
authors.lastname: Khomenko
authors.forename: S Yu
authors.initials: SY
authors.lastname: Mashina
authors.forename: D A
authors.initials: DA
authors.lastname: Pokidyshev
authors.forename: I Yu
authors.initials: IY
authors.lastname: Malyshev
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D003072:Cognition Disorders / Q000378:metabolism / Q000517:prevention & control*; D000860:Hypoxia / Q000503:physiopathology; D007501:Iron / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D009589:Nitrogen Oxides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D019335:Nitroarginine; D009569:Nitric Oxide; C073661:dinitrosyl iron complex; D007501:Iron; D019001:Nitric Oxide Synthase