Xiaomei Wu1, Ying Zhou2, Zhiling Huang1, Mingfei Cai1, Yi Shu1, Chang Zeng3, Li Feng4, Bo Xiao4, Qiong Zhan1. 1. Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China. 2. Department of Neurology, The First Hospital of Changsha, Changsha, China. 3. Health Management Center, Xiangya Hospital, Central South University, Changsha, China. 4. Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Abstract
BACKGROUND: The 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. METHODS: In 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. RESULTS: Our study revealed 3 principal findings. One, both α- and β-tubulin were decreased from the 3rd to the 30th day (lowest at the 7th day) in the seizure group compared with the controls. Two, both α- and β-tubulin were found to be more downregulated in the TLE-SRS and the TLE-NSRS group than in the control group (especially in the TLE-SRS group). The same trend was also noticed for hippocampal neuron loss. Three, the paclitaxel lowered the chronic SRS rate and increased the expression of PSD β-tubulin in the hippocampus. CONCLUSIONS: Altogether, 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. 2020 Annals of Translational Medicine. All rights reserved.
BACKGROUND: The 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. METHODS: In 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. RESULTS: Our study revealed 3 principal findings. One, both α- and β-tubulin were decreased from the 3rd to the 30th day (lowest at the 7th day) in the seizure group compared with the controls. Two, both α- and β-tubulin were found to be more downregulated in the TLE-SRS and the TLE-NSRS group than in the control group (especially in the TLE-SRS group). The same trend was also noticed for hippocampal neuron loss. Three, the paclitaxel lowered the chronic SRS rate and increased the expression of PSD β-tubulin in the hippocampus. CONCLUSIONS: Altogether, 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. 2020 Annals of Translational Medicine. All rights reserved.
Entities:
Keywords:
Colchicine; lithium-pilocarpine rat model; paclitaxel; α-tubulin; β-tubulin
Authors: M A Furtado; O W Castro; F Del Vecchio; J A Cortes de Oliveira; N Garcia-Cairasco Journal: Epilepsy Behav Date: 2011-01-14 Impact factor: 2.937
Authors: Dorothy P Schafer; Rashmi Bansal; Kristian L Hedstrom; Steven E Pfeiffer; Matthew N Rasband Journal: J Neurosci Date: 2004-03-31 Impact factor: 6.167