The study of microtubule dynamics and stability at the postsynaptic density in a rat pilocarpine model of temporal lobe epilepsy.

backgroundThe recurrence and drug resistance of temporal lobe epilepsy (TLE) has been ceaselessly challenging scientists and epilepsy experts. There has been an accumulation of evidence linking the dysregulation of postsynaptic proteins etiology and the pathology of epilepsy. For example, NMDA receptors, AMPA receptors, and metabotropic glutamate receptors (mGluRs). Furthermore, our earlier proteomic analysis proved there to be differential expressions of cytoskeletons like microtubules among rat groups. These differential expressions were shown in TLE-spontaneous recurrent seizures (TLE-SRS), TLE without SRS (TLE-NSRS) and control groups. Therefore, we aimed to understand how the microtubule system of the hippocampal postsynaptic density (PSD) regulates the development of TLE.

methodsIn this study, a pilocarpine-induced Sprague-Dawley rat TLE model were used, and Western blot, Nissl staining, and the immunoelectron microscopic method were utilized to determine the dynamic change of microtubules (α- and β-tubulin) in PSD and the extent of hippocampal neuron loss respectively in acute SE, and latent and chronic (spontaneous seizures) periods. Animal models were then stereotactically treated using colchicine, a microtubule depolymerizer, and paclitaxel, a microtubule polymerization agent, after each animal's acute SE period so as to further explore the function of PSD microtubules.

resultsOur study revealed 3 principal findings. One, both α- and β-tubulin were decreased from the 3

conclusionsAltogether, these results indicate that the microtubule system of PSD may play an essential role in the development and recurrence of epilepsy, and it may be used as a new target for the prevention and treatment of this refractory disease.