Patients with tuberous sclerosis complex (TSC) frequently have epilepsy that is poorly responsive to current therapies. To study the role of glia in epileptogenesis in TSC, we generated knockout mice with inactivation of the Tsc1 gene primarily in glia (Tsc1GFAPCKO mice). Tsc1GFAPCKO mice develop spontaneous seizures and exhibit a number of glial abnormalities that may promote epileptogenesis, including astrocyte proliferation, impaired astrocytic regulation of glutamate and potassium transport and homeostasis, and dysregulation of specific intracellular signaling pathways. These findings demonstrate the importance of glial-mediated mechanisms of epileptogenesis and suggest novel therapeutic targets for epilepsy directed at glial defects in TSC.
- Mouse model
- Tuberous sclerosis complex