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In both patients and murine models of <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>, the disease is associated with suppression of growth hormone (<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>) secretion, which is actively involved in the growth, development, and function of the central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>). Recent work showed that exogenous <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> therapy attenuated neurocognitive deficits elicited by <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content> during sleep in rats. Here, we show that administration of the Growth Hormone Releasing Hormone (<jats:styled-content style=\"fixed-case\">GHRH<\/jats:styled-content>) agonist <jats:styled-content style=\"fixed-case\">JI<\/jats:styled-content>\u201034 attenuates <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\u2010induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as <jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content> and 8\u2010hydroxydeoxyguanosine, and increases in hypoxia inducible factor\u20101\u03b1 <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> binding and up\u2010regulation of insulin growth factor\u20101 and erythropoietin expression. In contrast, treatment with a <jats:styled-content style=\"fixed-case\">GHRH<\/jats:styled-content> antagonist (<jats:styled-content style=\"fixed-case\">MIA<\/jats:styled-content>\u2010602) during intermittent hypoxia did not affect any of the <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\u2010induced deleterious effects in mice. Thus, exogenous <jats:styled-content style=\"fixed-case\">GHRH<\/jats:styled-content> administered as the formulation of a <jats:styled-content style=\"fixed-case\">GHRH<\/jats:styled-content> agonist may provide a viable therapeutic intervention to protect <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\u2010vulnerable brain regions from <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>\u2010associated neurocognitive dysfunction.<\/jats:p><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12360-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Sleep apnea, characterized by chronic intermittent hypoxia (IH), is associated with substantial cognitive and behavioral deficits. Here, we show that administration of a GHRH agonist (JI\u201034) reduces oxidative stress, increases both HIF\u20101\u03b1 nuclear binding and downstream expression of IGF1 and erythropoietin (EPO) in hippocampus and cortex, and markedly attenuates water maze performance deficits in mice exposed to intermittent hypoxia during sleep.<\/jats:p>","DOI":"10.1111\/jnc.12360","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T09:05:44Z","timestamp":1372755944000},"page":"531-540","source":"Crossref","is-referenced-by-count":47,"title":["Growth hormone releasing hormone (<scp>GHRH<\/scp>) signaling modulates intermittent hypoxia\u2010induced oxidative stress and cognitive deficits in mouse"],"prefix":"10.1111","volume":"127","author":[{"given":"Deepti","family":"Nair","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Pritzker School of Medicine University of Chicago Chicago Illinois 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