Impact of rapamycin on status epilepticus induced hippocampal pathology and weight gain.

Impact of rapamycin on status epilepticus induced hippocampal pathology and weight gain. Exp Neurol. 2016 Mar 16; Authors: Hester MS, Hosford BE, Santos VR, Singh SP, Rolle I, LaSarge CL, Liska JP, Garcia-Cairasco N, Danzer SC Abstract Growing evidence implicates the dentate gyrus in temporal lobe epilepsy (TLE). Dentate granule cells limit the amount of excitatory signaling through the hippocampus and exhibit striking neuroplastic changes that may impair this function during epileptogenesis. Furthermore, aberrant integration of newly-generated granule cells underlies the majority of dentate restructuring. Recently, attention has focused on the mammalian target of rapamycin (mTOR) signaling pathway as a potential mediator of epileptogenic change. Systemic administration of the mTOR inhibitor rapamycin has promising therapeutic potential, as it has been shown to reduce seizure frequency and seizure severity in rodent models. Here, we tested whether mTOR signaling facilitates abnormal development of granule cells during epileptogenesis. We also examined dentate inflammation and mossy cell death in the dentate hilus. To determine if mTOR activation is necessary for abnormal granule cell development, transgenic mice that harbored fluorescently-labeled adult-born granule cells were treated with rapamycin following pilocarpine-induced status epilepticus. Systemic rapamycin effectively blocked phosphorylation of S6 protein (a readout of mTO...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research