title: Expression of Glutamate Decarboxylase (GAD) mRNA in the brain of bile duct ligated rats serving as a model of hepatic encephalopathy.
abstract: Hepatic encephalopathy (HE) is a neurologic disorder that involves different pathophysiological mechanisms, including disturbances in the GABAergic neurotransmitter system. Albeit an overall increase in the level of neurotransmitter GABA has not been found in HE, alterations in GABA receptors and metabolism have been described. Moreover, it has been reported that bile duct ligated (BDL) rats, an animal model for the study of HE, exhibited an altered GABA biosynthesis involving preferentially the tricarboxylic (TCA) cycle. In this context it should be noted that the GABA synthesizing enzyme glutamate decarboxylase (GAD) is expressed in the brain in two isoforms GAD67 and GAD65, GAD65 being related to the synthesis of GABA that occurs via the TCA cycle and coupled to the vesicular pool of the neurotransmitter. The aim of the present study was to investigate whether changes in mRNA expression of GAD67 and GAD65 were related to the altered GABA biosynthesis previously observed. To study this, cerebral cortices and hippocampi were dissected from control and BDL rats, total mRNA was isolated and cDNA was synthesized by reverse transcription reaction. Subsequently samples were analyzed for gene expression of GAD67 and GAD65 by qPCR multiplex assay, using GAPDH as endogenous control. No changes in GAD67 and GAD65 mRNA expression between control and BDL rats either in cerebral cortex or in hippocampus were observed indicating that the HE condition did not lead to changes in GAD mRNA expression. However, other regulatory mechanism might be affecting GAD activity and to clarify this additional studies need to be conducted.
authors.affiliation: Experimental Hepatology and Gastroenterology Laboratory, Research Center of Hospital de Clínicas de Porto Alegre, Avenida Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-903, Brazil, renataleke@hotmail.com.
authors.forename: Renata
authors.initials: R
authors.lastname: Leke
authors.forename: Themis R
authors.initials: TR
authors.lastname: Silveira
authors.forename: Thayssa D C
authors.initials: TD
authors.lastname: Escobar
authors.forename: Arne
authors.initials: A
authors.lastname: Schousboe
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D008297:Male; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D005968:Glutamate Decarboxylase
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