Abstracts

Rationale: Seizure disorders are often associated with viral infections of the central nervous system (CNS). Up to 20% of patients who survive an initial viral infection of the CNS go on to develop epilepsy. C57BL/6 mice infected with the Daniels strain of Theiler’s murine encephalomyelitis virus (TMEV) have a 50% chance of developing spontaneous acute seizures between 3 and 10 days post infection (d.p.i.). After a latent period, 50% of the mice that present with seizures during the acute phase go on to develop spontaneous recurrent seizures. Therefore, the TMEV model represents a novel paradigm in which virus-host interactions leading to seizure development and epilepsy can be investigated.Methods: C57BL/6 mice were injected intracranially with either 20 μl TMEV (3.5x105 PFU) or PBS, and monitored for acute seizures using the Racine scale. Mice were sacrificed 6 d.p.i. and the hippocampi were dissected bilaterally. Hippocampi were homogenized and a total protein fraction aliquot was taken while the remaining sample underwent centrifugation to obtain a synaptosomal fraction. Expression levels of mGluR5 and GABRB3 were measured by western blot analysis using ImageJ, normalizing all samples to β-actin as a loading control.Results: We observed a significant decrease in synaptic mGluR5 and total GABRB3 expression levels in animals having seizures (N=5) 6 d.p.i. as compared to sham-injected animals (N=5). Animals that were infected, but did not develop seizures (N=4), did not show a significant difference from sham controls.Conclusions: Our results show that a decrease in mGluR5 and GABRB3 expression levels coincides with the development of acute seizures. These results suggest that changes in mGluR5 and GABRB3 receptor levels may cause a disruption in the balance between excitation and inhibition leading to seizures. Furthermore, we observed no significant changes in animals that were infected but did not develop seizures; indicating that synaptic changes coincide with seizure development and not viral infection alone. Our lab has previously shown that inflammatory mediators such as Interleukin-6 play a role in seizure development in the TMEV model. Future work will investigate the role of Interleukin-6 in receptor expression at the synapse.