Nitric oxide synthase and intermittent hypoxia-induced spatial learning deficits in the rat

Intermittent hypoxia (IH) during sleep induces significant neurobehavioral deficits in the rat. Since nitric oxide (NO) has been implicated in ischemia-reperfusion-related pathophysiological consequences, the temporal effects of IH (alternating 21% and 10% O 2 every 90 s) and sustained hypoxia (SH;...

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Bibliographic Details
Published in:Neurobiology of disease 2004-10, Vol.17 (1), p.44-53
Main Authors: Li, Richard C., Row, Barry W., Kheirandish, Leila, Brittian, Kenneth R., Gozal, Evelyne, Guo, Shang Z., Sachleben, Leroy R., Gozal, David
Format: Article
Language:English
Subjects:
Animals
Cerebral Cortex - chemistry
Cerebral Cortex - enzymology
eNOS
Hypoxia, Brain - enzymology
iNOS
Intermittent hypoxia
Knockout mice
Male
Maze Learning - physiology
Memory Disorders - enzymology
Mice
Mice, Knockout
Neurobehavioral deficits
Nitric Oxide Synthase - analysis
Nitric Oxide Synthase - deficiency
Nitric Oxide Synthase - genetics
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
nNOS
Rats
Rats, Sprague-Dawley
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Summary:Intermittent hypoxia (IH) during sleep induces significant neurobehavioral deficits in the rat. Since nitric oxide (NO) has been implicated in ischemia-reperfusion-related pathophysiological consequences, the temporal effects of IH (alternating 21% and 10% O 2 every 90 s) and sustained hypoxia (SH; 10% O 2) during sleep for up to 14 days on the induction of nitric oxide synthase (NOS) isoforms in the brain were examined in the cortex of Sprague–Dawley rats. No significant changes of endothelial NOS (eNOS) and neuronal NOS (nNOS) occurred over time with either IH or SH. Similarly, inducible NOS (iNOS) was not affected by SH. However, increased expression and activity of iNOS were observed on days 1 and 3 of IH ( P < 0.01 vs. control; n = 12/group) and were followed by a return to basal levels on days 7 and 14. Furthermore, IH-mediated neurobehavioral deficits in the water maze were significantly attenuated in iNOS knockout mice. We conclude that IH is associated with a time-dependent induction of iNOS and that the increased expression of iNOS may play a critical role in the early pathophysiological events leading to IH-mediated neurobehavioral deficits.
ISSN:0969-9961
1095-953X
DOI:10.1016/j.nbd.2004.05.006