Nitric oxide associated with iNOS expression inhibits acetylcholinesterase activity and induces memory impairment during acute hypobaric hypoxia

Abstract The mechanisms responsible for cholinergic dysfunction associated learning and memory impairment during hypoxia are not well-understood. However it is known that inflammatory mediators like inducible nitric oxide synthase (iNOS) hamper the functions of cholinergic neurons. In this present e...

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Bibliographic Details
Published in:Brain research 2008-09, Vol.1230, p.138-149
Main Authors: Udayabanu, M, Kumaran, D, Nair, R. Unnikrishnan, Srinivas, P, Bhagat, Neeta, Aneja, R, Katyal, Anju
Format: Article
Language:English
Subjects:
Acetylcholinesterase
Acetylcholinesterase - metabolism
Acute hypobaric hypoxia
Aminoguanidine
Amnesia, Anterograde - chemically induced
Amnesia, Anterograde - psychology
Amnesia, Retrograde - chemically induced
Amnesia, Retrograde - psychology
Animals
Avoidance Learning - drug effects
Behavioral psychophysiology
Biological and medical sciences
Blotting, Western
Cerebral Cortex - drug effects
Cerebral Cortex - enzymology
Cholinesterase Inhibitors - pharmacology
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
Glyceraldehyde-3-Phosphate Dehydrogenases - biosynthesis
Glyceraldehyde-3-Phosphate Dehydrogenases - genetics
Guanidines - pharmacology
Hippocampus - drug effects
Hippocampus - enzymology
Hypoxia - enzymology
Hypoxia - psychology
Inducible nitric oxide synthase
Learning - drug effects
Lipid Peroxidation - drug effects
Male
Memory Disorders - chemically induced
Memory Disorders - psychology
Mice
Mice, Inbred BALB C
Neurology
Neurotransmission and behavior
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Donors - pharmacology
Nitric Oxide Synthase Type II - antagonists & inhibitors
Nitric Oxide Synthase Type II - biosynthesis
Oxidative Stress - drug effects
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Retrograde memory
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
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Summary:Abstract The mechanisms responsible for cholinergic dysfunction associated learning and memory impairment during hypoxia are not well-understood. However it is known that inflammatory mediators like inducible nitric oxide synthase (iNOS) hamper the functions of cholinergic neurons. In this present experiment we made an effort to study the iNOS expression mediated retrograde and anterograde memory impairment in Balb/c mice following acute hypobaric hypoxia (at an altitude of 23,000ft for 6h) using elevated plus maze and passive avoidance step-through tasks. Our results demonstrated that hypoxia transiently impairs the retrograde memory without affecting the anterograde memory functions, accompanied with a substantial rise in iNOS expression and nitric oxide levels in cerebral cortex on days 2 and 3 post hypoxia. Treatment with aminoguanidine (iNOS inhibitor ), resulted in down-regulation of the iNOS expression, attenuation of the surge of nitric oxide (NO) in cerebral cortex and reversal of retrograde memory impairment due to hypoxia. Moreover the reduced AChE activity and elevated lipid peroxidation in cerebral cortex were evident during post hypoxia re-oxygenation period, which was not observed in the hippocampus. Additionally, NO donor spermine NONOate could inhibit the AChE activity in brain homogenates in a concentration-dependent manner, which further substantiate that nitric oxide produced during post hypoxia re-oxygenation, primarily contributes to the observed inhibition of cortical AChE activity. Based on these experiments we hypothesize that the NO burst as a result of iNOS upregulation during hypoxia interrupts the memory consolidation by altering the cholinergic functions.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2008.06.081