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Green Tea Catechin Polyphenols Attenuate Behavioral and Oxidative Responses to Intermittent Hypoxia

¹ Department of Pediatrics, Kosair Children's Hospital Research Institute, and ² Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky; and ³ Department of Pediatrics, Soroka University Medical Center, Beer-Sheva, Israel

Correspondence and requests for reprints should be addressed to David Gozal, M.D., Kosair Children's Hospital Research Institute, University of Louisville, 570 South Preston Street, Suite 204, Louisville, KY 40202. E-mail: david.gozal{at}louisville.edu

Rationale: The intermittent hypoxia (IH) that characterizes sleep-disordered breathing impairs spatial learning and increases NADPH oxidase activity and oxidative stress in rodents. We hypothesized that green tea catechin polyphenols (GTPs) may attenuate IH-induced neurobehavioral deficits by reducing IH-induced NADPH oxidase expression, lipid peroxidation, and inflammation.

Objectives: To assess the effects of GTP administered in drinking water on the cognitive, inflammatory, and oxidative responses to long-term (>14 d) IH during sleep in male Sprague-Dawley rats.

Methods: Cognitive assessments were conducted in the Morris water maze. We measured levels and expression of malondialdehyde (MDA), prostaglandin E₂, p47^phox subunit of NADPH oxidase, receptor for advanced glycation end products (RAGE), and glial fibrillary acidic protein expression in rodent brain tissue.

Measurements and Main Results: GTP treatment prevented IH-induced decreases in spatial bias for the hidden platform during the Morris water maze probe trails as well as IH-induced increases in p47phox expression within the hippocampal CA1 region. In untreated animals, IH exposure was associated with doubling of cortical MDA levels in comparison to room air control animals, and GTP-treated animals exposed to IH showed a 40% reduction in MDA levels. Increases in brain RAGE and glial fibrillary acidic protein expression were observed in IH-exposed animals, and these increases were attenuated in animals treated with GTP.

Conclusions: Oral GTP attenuates IH-induced spatial learning deficits and mitigates IH-induced oxidative stress through multiple beneficial effects on oxidant pathways. Because oxidative processes underlie neurocognitive deficits associated with IH, the potential therapeutic role of GTP in sleep-disordered breathing deserves further exploration.

Key Words: sleep apnea • cognition • inflammation • oxidative stress • hypoxia

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Sleep apnea is associated with neurocognitive deficits that are mediated at least in part by increased oxidative stress. It remains unclear how lifestyle issues such as dietary habits modify the susceptibility to the disease. What This Study Adds to the Field Oral supplements of green tea–derived polyphenols reduces the neural susceptibility to intermittent hypoxia during sleep in rodents.