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1Section of Respiratory Medicine, Department of Pediatrics, and 4Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520; 3Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215; and2Section of Respiratory Medicine, Department of Pediatrics, and5Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461
Submitted 27 November 2002 ; accepted in final form 27 March 2003
Chronic intermittent hypoxia (CIH) is a component of several disease states, including obstructive sleep apnea, which results in neurocognitive and cardiovascular morbidity. Because chronic hypoxia can induce changes in metabolism and pH homeostasis, we hypothesized that CIH induces changes in the expression of acid-base transporters. Two- to three-day-old mice, exposed to alternating cycles of 2 min of hypoxia (6.0–7.5% O2) and 3 min of normoxia (21% O2) for 8 h/day for 28 days, demonstrated decreases in specific acid-base transport protein expression in most of the central nervous system (CNS). Sodium/hydrogen exchanger isoform 1 (NHE1) and sodium-bicarbonate cotransporter expression were decreased in all regions of the CNS but especially so in the cerebellum. NHE3, which is only expressed in the cerebellum, was also significantly decreased. Anion exchanger 3 protein was decreased in most brain regions, with the decrease being substantial in the hippocampus. These results indicate that CIH induces downregulation of the major acid-extruding transport proteins, NHE1 and sodium-bicarbonate cotransporter, in particular regions of the CNS. This downregulation in acid-extruding capacity may render neurons more prone to acidity and possibly to injury during CIH, especially in the cerebellum and hippocampus. Alternatively, it is possible that O2 consumption in these regions is decreased after CIH, with consequential downregulation in the expression of certain cellular proteins that may be less needed under such circumstances.
brain; cyclical hypoxia; proteins; central nervous system
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