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Astrocytes are a major cellular target of hyperammonemic encephalopathy, and changes occurring in these cells are thought to be causally related to the brain edema of acute HA. To study the effect of HA on astrocytes <jats:italic>in vivo<\/jats:italic>, we crossed the <jats:italic>Otc<jats:sup>spf<\/jats:sup><\/jats:italic> mouse, a mouse with the X\u2010linked UCD ornithine transcarbamylase (OTC) deficiency, with the hGFAP\u2010EGFP mouse, a mouse selectively expressing green fluorescent protein in astrocytes. We used FACS to purify astrocytes from the brains of hyperammonemic and healthy <jats:italic>Otc<jats:sup>spf<\/jats:sup><\/jats:italic>\/GFAP\u2010EGFP mice. RNA isolated from these astrocytes was used in microarray expression analyses and qRT\u2010PCR. When compared with healthy littermates, we observed a significant downregulation of the gap\u2010junction channel connexin 43 (<jats:italic>Cx43<\/jats:italic>) the water channel aquaporin 4 (<jats:italic>Aqp4<\/jats:italic>) genes, and the astrocytic inward\u2010rectifying potassium channel (Kir) genes <jats:italic>Kir4.1<\/jats:italic> and <jats:italic>Kir5.1<\/jats:italic> in hyperammonemic mice. Aqp4, Cx43, and Kir4.1\/Kir5.1 are co\u2010localized to astrocytic end\u2010feet at the brain vasculature, where they regulate potassium and water transport. Since, NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup> ions can permeate water and K<jats:sup>+<\/jats:sup>\u2010channels, downregulation of these three channels may be a direct effect of elevated blood ammonia levels. Our results suggest that alterations in astrocyte\u2010mediated water and potassium homeostasis in brain may be key to the development of the brain edema. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20624","type":"journal-article","created":{"date-parts":[[2008,1,9]],"date-time":"2008-01-09T18:16:29Z","timestamp":1199902589000},"page":"365-377","source":"Crossref","is-referenced-by-count":79,"title":["Gene expression profiling of astrocytes from hyperammonemic mice reveals altered pathways for water and potassium homeostasis <i>in vivo<\/i>"],"prefix":"10.1002","volume":"56","author":[{"given":"Uta","family":"Lichter\u2010Konecki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean 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