Altered Astrocyte-Neuron Interactions and Epileptogenesis in Tuberous Sclerosis Complex Disorder.

摘要

This report is on the second year of our 2011 Tuberous Sclerosis Complex Research Program Idea Development Award (07/12-6/15). The original goals are to explore the potential mechanism for epileptogenesis in Tuberous Sclerosis Complex (TSC) disease, with a focus on altered astrocyte-neuronal interactions caused by astrocyte-specific TSC deficiency. Our hypothesis is that abnormal cells in non-tuber cortex might form an abnormally excitable network that underlies seizure generation in TSC. Epileptogenesis in non-tuber neural tissue in TS may thus arise by an imbalance of decreased inhibitory and increased excitatory synaptic transmission. Astrocytes could also regulate neuronal excitability by glutamate uptake and other means that alter expression and function of synaptic receptors for glutamate, or by altering the number of synapses. A deficiency of GABAergic interneurons, a possible downstream consequence of altered mTOR activity in astrocytes, may further contribute to the early onset and severity of seizures in TS.