{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T22:18:39Z","timestamp":1773958719088,"version":"3.50.1"},"reference-count":57,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:p> 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\u20137.5% O<jats:sub>2<\/jats:sub>) and 3 min of normoxia (21% O<jats:sub>2<\/jats:sub>) 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 O<jats:sub>2<\/jats:sub> 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. <\/jats:p>","DOI":"10.1152\/japplphysiol.01089.2002","type":"journal-article","created":{"date-parts":[[2015,7,15]],"date-time":"2015-07-15T17:28:26Z","timestamp":1436981306000},"page":"292-299","source":"Crossref","is-referenced-by-count":39,"title":["Chronic intermittent hypoxia decreases the expression of Na\/H exchangers  and HCO<sub>3<\/sub>-dependent transporters in mouse CNS"],"prefix":"10.1152","volume":"95","author":[{"given":"R. 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J Exp  Biol 201:  1141-1152, 1998."},{"key":"REF8","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1993.265.5.F736"},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1992.263.5.F833"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02350-7"},{"key":"REF11","unstructured":"Boron WF.  Sodium-coupled bicarbonate transporters. JOP 2: 176-181,  2001."},{"key":"REF12","unstructured":"Cervos-Navarro J and Diemer NH. Selective vulnerability in brain  hypoxia. Crit Rev Neurobiol 6:  149-182, 1991."},{"key":"REF13","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(90)90034-E"},{"key":"REF14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.3.C576"},{"key":"REF15","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.5.1890"},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.1.1"},{"key":"REF17","unstructured":"Deitmer JW.  pH regulation in invertebrate glia. In: pH and Brain  Function, edited by Kaila K and Ransom BR. New York: Wiley-Liss,  1998, p. 233-252."},{"key":"REF18","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00473-5"},{"key":"REF19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.280.5.R1555"},{"key":"REF20","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(02)00361-9"},{"key":"REF21","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)91276-M"},{"key":"REF22","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00352.2002"},{"key":"REF23","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.5.1995"},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)01853-5"},{"key":"REF25","unstructured":"Grassl SM and  Aronson PS. \\batchmode \\documentclass[fleqn,10pt,legalpaper]{article} \\usepackage{amssymb} \\usepackage{amsfonts} \\usepackage{amsmath} \\pagestyle{empty} \\begin{document} \\(\\mathrm{Na}^{+}\/\\mathrm{HCO}_{3}^{-}\\) \\end{document}  co-transport in basolateral membrane vesicles isolated from rabbit renal  cortex. 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Oxidative stress in the fetal lamb brain following intermittent umbilical cord  occlusion: a path analysis. Br J Obstet Gynaecol 108: 1283-1290,  2001."},{"key":"REF47","doi-asserted-by":"publisher","DOI":"10.1038\/387409a0"},{"key":"REF48","unstructured":"Rose CR and  Ransom BR. pH regulation in mammalian glia. In: pH and Brain  Function, edited by Kaila K and Ransom BR. New York: Wiley-Liss,  1998, p. 253-275."},{"key":"REF49","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(00)00302-8"},{"key":"REF50","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200209000-00024"},{"key":"REF51","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.276.1.H27"},{"key":"REF52","doi-asserted-by":"crossref","unstructured":"Siesj\u00f6 BK,  Katsura K, Mellergard P, Elholm A, Lundgren J, and Smith ML.  Acidosis-related brain damage. 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