Rapamycin reveals an mTOR-independent repression of Kv1.1 expression during Epileptogenesis

International Conference on Epilepsy & Treatment

September 21-22, 2015 Baltimore, USA

Raab-Graham K F, Brager D H, Wolfe S, Niere F and Sosanya N M

University of Texas, USA

Posters-Accepted Abstracts: J Neurol Disord

Abstract :

mTOR signaling is overactive and thought to be, at least in part, the underlying cause of several developmental and neurodegenerative diseases. mTOR is best characterized for its role in promoting translation of mRNAs. Therefore, it is often hypothesized that overactive mTOR in neurological disorders results in excessive protein synthesis. However, a number of studies suggest that there is a reduction or loss of protein expression with respect to voltage-gated ion channels. Previously, we demonstrated that mTOR activity represses the local translation of the voltage-gated potassium channel Kv1.1 in neuronal dendrites. Herein we demonstrate that in the hippocampus mTOR activity mediates the first phase of Kv1.1 repression in a rat model of temporal lobe epilepsy. This is followed by a second, mTOR-independent phase. Decreased Kv1.1 expression results in a reduced threshold for firing an action potential. Treatment with the mTOR inhibitor rapamycin decreases behavioral seizures and increases Kv1.1 expression, but only initially. Unexpectedly, we found that miR-129-5p levels, the microRNA that represses Kv1.1 mRNA translation, continue to rise even in the presence of rapamycin. The increase in miR-129-5p corresponded to an increase in seizure activity and a reduction in Kv1.1 expression during later stages of epileptogenesis. Our findings are the first to demonstrate a novel mTOR-independent phase in epileptogenesis and provide the molecular basis for the biphasic nature of Kv1.1 repression in temporal lobe epilepsy.

Biography :

Email: kimberly@mail.clm.utexas.edu