| Description |
A large number of epilepsy patients are resistant to treatment, and even more contend daily with medication side-effects. Novel treatments are needed and continued investigation into novel, non-neuronal targets is essential. Astrocytes mediate glutamate homeostasis and are thus of great interest in the search to identify seizure mechanisms and drug targets. Astrocytes can release glutamate via the system xc- transporter, as well as take it up via glutamate transporter 1 (GLT-1). Changes in astrocyte glutamate homeostasis has been implicated in neuronal injury and hyperexcitability in temporal lobe epilepsy. However, this is controversial, potentially due to differing methodologies, or due to astrocyte heterogeneity. Thus, we will investigate whether increasing glutamate uptake via a pharmacological tool, or decreasing glutamate export via a genetic manipulation, reduces seizure burdens, gliosis, or neuronal injury in a model of temporal lobe epilepsy. Our findings suggest modulating glutamate uptake or release is not sufficient to change outcomes in the Theiler's Murine Encephalomyelitis Virus (TMEV) model. However, further investigations into astrocyte mechanisms in epilepsy are necessary and important. |
