title: Loss of expression of glial fibrillary acidic protein in acute hyperammonemia.
abstract: Glial fibrillary acid protein (GFAP) is a major component of the glial filament network and alterations in expression of this protein in cultured astrocytes have been reported in response to acute ammonia exposure in vitro. In order to determine the effects of acute hyperammonemia in vivo on GFAP expression, brain extracts from rats with acute liver failure due to hepatic devascularization (portacaval anastomosis followed 24h later by hepatic artery ligation, HAL) were analyzed for GFAP mRNA using reverse transcription-polymerase chain reaction (RT-PCR) and appropriate oligonucleotide primers. GFAP protein was assayed by immunoblotting using a polyclonal antibody. Hepatic devascularization resulted in a significant 55-68% decrease (P<0.01) of GFAP mRNA and a concomitant loss of GFAP protein at precoma and coma stages of encephalopathy when brain water content was significantly increased and brain ammonia concentrations were in the millimolar range (1-5mM). Expression of a second glial filament protein S-100beta was unaffected by acute hyperammonemia. These findings suggest a role for GFAP in cell volume regulation and that loss of GFAP expression could contribute to the pathogenesis of brain edema in acute hyperammonemic syndromes.
authors.affiliation: Neuroscience Research Unit, Hôpital Saint-Luc du Chum, University of Montreal, 1058 St-Denis Street, Que., H2X 3J4, Montreal, Canada.
authors.forename: Mireille
authors.initials: M
authors.lastname: Bélanger
authors.forename: Paul
authors.initials: P
authors.lastname: Desjardins
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chatauret
authors.forename: Roger F
authors.initials: RF
authors.lastname: Butterworth
mesh_terms: D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000378:metabolism; D022124:Hyperammonemia / Q000378:metabolism*; D017093:Liver Failure / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger