Intermittent Hypoxia Is Associated with Oxidative Stress and Spatial Learning Deficits in the Rat

• Published in: American journal of respiratory and critical care medicine 2003-06, Vol.167 (11), p.1548-1553
• Main Authors: Row, Barry W, Liu, Rugao, Xu, Wei, Kheirandish, Leila, Gozal, David
• Format: Article
• Language: English
• Subjects: Airway management; Animals; Biological and medical sciences; Hypoxia; Hypoxia - physiopathology; Laboratory animals; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipids; Male; Maze Learning - physiology; Medical sciences; Memory; Oxidative stress; Oxidative Stress - physiology; Pneumology; Pyrimidines - therapeutic use; Pyrroles - therapeutic use; Rats; Rats, Sprague-Dawley; Respiratory system : syndromes and miscellaneous diseases; Sleep apnea; Sleep Apnea Syndromes - physiopathology; Sleep disorders; Spatial Behavior - physiology
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200209-1050OC

In the adult rat, exposure to intermittent hypoxia (IH), such as occurs in sleep-disordered breathing, is associated with neurobehavioral impairments and increased apoptosis in the hippocampal CA1 region and cortex. We hypothesized that the episodic hypoxic-reoxygenation cycles of IH would induce oxidant stress, and the latter may underlie the IH-associated spatial learning and retention deficits. Adult male rats were therefore exposed to IH (90-second alternations of 10% oxygen and 21% oxygen) or room air (RA) for 7 days, and received twice-daily injections of either 3 mg/kg of the antioxidant PNU-101033E (PNU) or vehicle (V). Rats were then trained in a standard place-training task in the water maze. V-IH displayed significant impairments of spatial learning in the water maze, which were attenuated by PNU-101033E. Post hoc analyses further revealed that V-IH had significantly longer latencies and pathlengths to locate the hidden platform than PNU-IH, V-RA, or PNU-RA, indicating that PNU-101033E treatment reduced the behavioral impairments associated with IH. In addition, treatment with PNU-101033E markedly attenuated the increase in lipid peroxidation, and isoprostane concentrations associated with exposure to IH. Collectively, these findings indicate that the IH exposure is associated with increased oxidative stress, which is likely to play an important role in the behavioral impairments observed in a rodent model of sleep-disordered breathing.