Role of astrocytic glutamate transporters in acute liver failure

• Grant number: 12/15406-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2012
• End date: August 31, 2013
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Alan Stewart Hazell
• Grantee: Guilherme Soares de Oliveira Wertheimer
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Acute liver failure (ALF) arising from viral infection or toxic liver injury is a serious metabolic disorder with life-threatening consequences. Hepatic encephalopathy (HE) and the associated cerebral edema arising from ALF demands immediate attention usually necessitating emergency liver transplantation. Understanding the pathophysiology of this disorder is necessary in order to develop rational therapeutic strategies. This project aims to demonstrate that the elevation of the ammonia concentration in the ALF halts the glutamatergic neurotransmission by diminishing the glutamate transporter splice-variant GLT-1v. The event will be evaluated by immunoblotting of brains belonging to C57BL male mice treated with azoxymethane (AOM), a well established experimental model to study ALF; and primary cultures of astrocytes treated with ammonia and then siRNA specific to GLT-1 to study the effects of the knockdown in uptake and release of glutamate by the transporter. The experiments will bring a better understanding of the pathophysiological mechanisms responsible for encephalopathy and brain edema in ALF.(AU)