Mesial Temporal Lobe Epilepsy Model Rat Study The Role Of MTOR And Wnt / β-catenin Signaling Pathway In The Pathogenesis Of Mesial Temporal Lobe Epilepsy Application Kainic Acid Induced

Epilepsy is a chronic neurological disease characterized by dysfunction of central nervous system, that caused by excessive hyper-synchronous neuronal activity neurons in brain. Mesial temporal lobe epilepsy (mTLE) is the main type of epilepsy, and the most common kind of medically intractable epilepsy. The mechanisms underlying have not yet been understood. The clinical researches indicated that80%mesial temporal lobe epilepsy patients have a similar pathological changes called hippocamal sclerosis, that characterized by astrogliosis, neurodegeneration, granule cell dispersion and mossy fiber sprouting. So, it is very important to realize the mechanism of mesial temporal lobe epilepsy by the further research of hippocaml sclerosis. Recently, researches indicated that the activity of mTOR signaling pathway has been increased, and inhibited the activity of mTOR signaling pathway is the effective way to decrease the extent of neurodegeneration, mossy fiber sprouting and the spontaneous seizure caused by kainate acid. So it is very important to understand the mechanism of mTLE by spatio-temporal pattern research of mTOR signaling pathway. Besides, the researches of Wnt/β-catenin signaling pathay indicated that it can stimulate neural stem cell proliferation and self-renewal, can regulate the morphogenesis of dendrite and regulates excitatory postsynaptic strength at hippocampal synapses. So it is also very important to understand the mechanism of mTLE by the research of Wnt/β-catenin signaling pathway.According to the pathologic features, selecting the mTOR and Wnt/β-catenin as the target pathway to study by western blotting analysis, immunohistochemistry and immunofluorescence analysis.Results:(1) mTLE model mice were successfully established by introhippocampal injection of kainate acid;(2) excessive activation of mTOR was observed in subregion of hippocampus on acute phase, latent phase and chronic phase of model mice;(3) all sclerotic hippocampi displayed excessive activation of mTOR in reactive atrocities, and reactive astrocytes with upregulated mTOR not only appeared in non-neuronal layers, but also invaded the dispersed dentate gyrus;(4) the expression of Wnt/β-catenin between control and case among model mice and mTLE patients without any difference.Our results indicate that:(1) mTOR activation may plays multiple roles in epileptogenesis, and targeted inactivation of mTOR in astrocytes as a potential therapeutic strategy for treatment of this disease.(2) Wnt/β-catenin maybe not involved in the epileptogenesis of mTLE.