Changes in glial glutamate transporters protein levels in TMEV model of viral-induced epilepsy

Abstract

Event Abstract Back to Event Changes in glial glutamate transporters protein levels in TMEV model of viral-induced epilepsy Giulia Albertini1*, Jaycie Loewen2, Joeri Van Liefferinge1, Eduard Bentea3, Thomas Demuyser1, Ellen Merckx3, Lauren Deneyer3, Ilse J. Smolders1, Karen S. Wilcox2 and Ann Massie3 1 Vrije Universiteit Brussel, Department of Pharmaceutical Chemistry and Drug Analysis, Belgium 2 University of Utah, Department of Pharmacology & Toxicology, United States 3 Vrije Universiteit Brussel, Department of Pharmaceutical Biotechnology and Molecular Biology, Belgium Viral encephalitis is often associated with seizures and increased risk of developing chronic epilepsy. Intracerebral (i.c) infections of Daniel (DA) strain of Theiler’s murine encephalomyelitis virus (TMEV) in susceptible strains of mice cause acute encephalitis followed by a chronic inflammatory demyelinating disease with persistence of the virus (1). Recently it has been shown that C57BL/6 (B6) mice are resistant to TMEV-induced demyelination and, after developing an acute disease characterized by tonic-clonic seizures, are able to clear the virus within 2 weeks post-infection (p.i.). Interestingly, TMEV infection chronically alters seizure susceptibility and a significant proportion of mice develop spontaneous seizures, establishing the TMEV model in B6 mice as a valid model of viral-induced epilepsy (Figure 1). Astrocytes seem to play a key role in demyelination resistance because, compared to other strains of mice, B6 display an enhanced astrocytic anti-viral response that might contribute to their ability to clear TMEV (2). Nevertheless the mechanisms involved in acute seizures and epilepsy development have not been elucidated yet within this model. Increased extracellular glutamate levels in the synaptic cleft are thought to play a major role in epilepsy potentially leading to hyperexcitability and excitotoxicity at seizure foci and increased excitation due to altered glutamate transporters has been described in several animal models of epilepsy (3). The aim of our work was to unravel the involvement of glial glutamate transporters in the TMEV model of viral-induced epilepsy. Therefore, protein expression levels of GLAST and GLT1, two glutamate reuptake transporters, and xCT, the functional subunit of cystine/glutamate antiporter or system xc- which is the main source of extracellular glutamate in mouse hippocampus, were investigated by Western Blotting. Cortical, hippocampal and cerebellar samples were collected during the acute phase (5 days p.i.), the clearance phase (14 days p.i.) and the chronic phase (2 months p.i.) of B6 mice infected with DA strain of TMEV and compared with their mock-infected littermates. Our findings (Table 1) show changes in glial glutamate transporters expression that may be involved in seizure generation and development of subsequent epilepsy. Further research is needed to elucidate whether increased levels of system xc- together with changes in glutamate re-uptake carriers lead to a rise in extracellular glutamate levels and hyperexcitability in viral-induced epilepsy. Figure 1