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Show SPRING 2013 Changes in Metabotropic Glutamate Receptor 5 Expression in Astrocytes Following Theiler Virus Infection of C57BL/6 Mice B1, Primary Investigator: John A. White, PhD1-2 Bring, University of Utah, Salt Lake City, Utah stitute, Salt Lake City, Utah u T H E U N I V E R S I T Y O E U T AH J Introduction gaB *m • * ! Methods 26 and GFAP (.I*] ThEV-iAMCttd ConUOl TUEV-fiKtM I- • Results Discussion aKa"i5V K&& ' 1 - ' f "-- !••••»••• Acknowledgements Ii I ll' l l a C S References CHANGES IN METABOTROPIC GLUTAMATE RECEPTOR 5 EXPRESSION IN ASTROCYTES FOLLOWING THEILER VIRUS INFECTION OF C57BL/6 MICE Marsa Taheri, (John White) Department of Bioengineering University of Utah Acquired epilepsy, caused by prior neurological injuries such as viral infection of the central nervous system (CNS), contributes to almost half of all epilepsy cases. A prevalent form of acquired epilepsy is temporal lobe epilepsy (TLE), which is often resistant to available drugs [1,2]. Although the molecular mechanisms underlying humanTLE are largely unknown, evidence shows that astrocytes (the predominant glial cell type in the brain) are likely to be involved in epileptogenesis-the process by which a normal brain becomes epileptic [3,4,5,6]. Metabotropic glutamate receptor 5 (mGluR5) in astrocytes is thought to be particularly important in inducing excessive astrocytic Ca+2 signaling, which may lead to neuronal hyperexcitability associated with epilepsy [5,7,8]. The goal of our study is to better understand the role that astrocytes, and particularly astrocytic play in epileptogenesis. For this study, w e examined the Theiler's murine encephalomyelitis virus (TMEV)- induced seizure model in C57BI/6 mice during the latent period, in which epileptogenesis occurs. W e used immunohistochemistry, confocal microscopy, and image processing techniques to quantify the expression levels of astrocytic mGluR5 and to detect astrocyte morphological changes as determined by the expression of GFAP (glial fibrillary acidic protein). In brain slices obtained from two TMEV-injected mice and one control mouse, w e found increased GFAP expression and morphology modifications in hippocampal astrocytes as well as increased mGluR5 expression in these astrocytes. While more animals are needed to determine the significance of our results, these findings suggest that changes in astrocyte mGluR5 expression may be an important factor in the development of behavioral seizures in epilepsy. REFERENCES [1] Stewart KA, Wilcox KS, Fujinami RS, White HS. Development of Post-infection Epilepsy Following Theiler Virus Infection of C57BL/6 Mice. J Neuropathol Exp Neurol. 2010 Dec; 69(12):1210-9. [2] Schmidt D, Lbscher W. Drug resistance in epilepsy: putative neurobiologic and clinical mechanisms. Epilepsia. 2005 Jun; 46(6):858-77. [3] Nedergaard M, Verkhratsky A. Artifact Versus Reality-How Astrocytes Contribute to Synaptic Events. Glia. 2012 Jul; 60(7):1013-23. [4] Ricci G, Volpi L, Pasquali L, et al. Astrocyte-Neuron Interactions in Neurological Disorders. J Biol Phys. 2009 Oct; 35(4):317-36. [5] Notenboom RG, Hampson DR, Jansen GH, et al. Up-regulation of hippocampal metabotropic glutamate receptor 5 in temporal lobe epilepsy patients. Brain. 2006 Jan; 129(Pt 1 ):96-107. [6] McNamara JO, Huang YZ, Leonard AS. Molecular Signaling Mechanisms Underlying Epileptogenesis. Sci STKE. 2006 Oct; 2006(356):re12. [7] Ding S, Fellin T, Zhu Y, et al. Enhanced Astrocytic Ca2+ Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus J Neuroscience 2007 Oct; 27(40):10674-10684. [8] Aronica E, van Vliet EA, Mayboroda OA, et al. Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in reactive astrocytes in model of mesial temporal lobe epilepsy. Eur J Neurosci. 2000 Jul; 12(7):2333-44. [9] Libbey JE, Kirkman NJ, Smith MC, et al. Seizures following Picornavirus Infection. Epilepsia. 2008 Jun; 49(6): 1066-74. [10] Rattka M, Brandt C, Lbscher W. Do proconvulsants modify or halt epileptogenesis? Pentylenetetrazole is ineffective in two rat models of temporal lobe epilepsy. Eur J Neurosci. 2012 Aug; 36(4):2505-20. |