Dataset Information

MicroRNA expression profile of the hippocampus in a rat model of temporal lobe epilepsy and miR-34a-targeted neuroprotection against hippocampal neurone cell apoptosis post-status epilepticus.

ABSTRACT:

Background

The expression pattern and function of miRNAs in the rat model of temporal lobe epilepsy have not been well defined. Profiling miRNA expression in the rat model of temporal lobe epilepsy and investigating the function of specific miRNAs in epilepsy offers the prospect of a deeper understanding of the mechanisms of epilepsy.

Methods

The lithium-pilocarpine-induced status epilepticus model and the temporal lobe epilepsy model were established in Sprague-Dawley rats. Samples were analysed to detect deregulated miRNAs in the hippocampal temporal lobe, and several of these deregulated miRNAs were confirmed by qPCR. The expression of the pro-apoptotic miR-34a was detected at 1?day, 7?days and 2?weeks post-status epilepticus and at 2?months after temporal lobe epilepsy. The antagomir of miR-34a was then utilised. The expression of miR-34a after targeting and the expression change of activated caspase-3 protein were examined. The effects of altering the expression of miR-34a and activated caspase-3 protein on neuronal survival and neuronal death or apoptosis post-status epilepticus were assessed.

Results

The miRNA microarray detected 9 up-regulated miRNAs (miR-146a, -211, -203, -210, -152, -31, -23a, -34a, -27a) and 15 down-regulated miRNAs (miR-138*, -301a, -136, -153, -19a, -135b, -325-5p, -380, -190, -542-3p, -33, -144, -542-5p, -543, -296*). Some of the deregulated miRNAs (miR-146a, miR-210, miR-27a, miR-135b and miR-33) were confirmed using qPCR. Furthermore, an increase in expression of the pro-apoptotic miR-34a was demonstrated in the post-status epilepticus rat hippocampus. miR-34a was significantly up-regulated at 1?day, 7?days and 2?weeks post-status epilepticus and at 2?months after temporal lobe epilepsy. Experiments with the miR-34a antagomir revealed that targeting miR-34a led to an inhibition of activated caspase-3 protein expression, which may contribute to increased neuronal survival and reduced neuronal death or apoptosis.

Conclusions

Our study showed the expression profile of miRNAs in the hippocampus in a rat model of temporal lobe epilepsy and an increase in the expression of the pro-apoptotic miR-34a in post-status epilepticus rats. The results show that miR-34a is up-regulated during seizure-induced neuronal death or apoptosis, and targeting miR-34a is neuroprotective and is associated with an inhibition of an increase in activated caspase-3 protein.

SUBMITTER: Hu K

PROVIDER: S-EPMC3471047 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Publications

MicroRNA expression profile of the hippocampus in a rat model of temporal lobe epilepsy and miR-34a-targeted neuroprotection against hippocampal neurone cell apoptosis post-status epilepticus.

Hu Kai K Xie Yuan-Yuan YY Zhang Chen C Ouyang Dong-Sheng DS Long Hong-Yu HY Sun Dan-Ni DN Long Li-Li LL Feng Li L Li Yi Y Xiao Bo B

BMC neuroscience 20120922

<h4>Background</h4>The expression pattern and function of miRNAs in the rat model of temporal lobe epilepsy have not been well defined. Profiling miRNA expression in the rat model of temporal lobe epilepsy and investigating the function of specific miRNAs in epilepsy offers the prospect of a deeper understanding of the mechanisms of epilepsy.<h4>Methods</h4>The lithium-pilocarpine-induced status epilepticus model and the temporal lobe epilepsy model were established in Sprague-Dawley rats. Sampl ...[more]

PMID: 22998082

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Project description:Background and purposeUnilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.Materials and methodsFifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively.ResultsCompared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized β = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized β = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity (F2,12 = 0.284, P = .757, R2 = 0.045).ConclusionsIn left mesial temporal lobe epilepsy with hippocampal sclerosis, the left inferior cingulum bundle undergoes degeneration in tandem with the left hippocampal volume, whereas intrinsic functional connectivity seems to react by compensating the loss of connectivity. Such insight might be helpful in understanding the development of the epileptic network in left mesial temporal lobe epilepsy with hippocampal sclerosis.

Project description:Background andObjective: In the present study, a detailed investigation of substructural volume change in the hippocampus (HC) and amygdala (AMG) was performed and the association with clinical features in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) determined. Methods: The present study included 22 patients with left-sided TLE-HS (LTLE-HS) and 26 patients with right-sided TLE-HS (RTLE-HS). In addition, 28 healthy controls underwent high-resolution T2-weighted image (T2WI) and T1-weighted image (T1WI) MRI scanning. Subfield analysis of HC and AMG was performed using FreeSurfer version 6.0. Results: Patients with TLE-HS showed a decrease in the volume of substructures in both HC and AMG, and this change was observed on the contralateral side and the ipsilateral side with HS. The volume reduction pattern of substructures showed laterality-dependent characteristics. Patients with LTLE-HS had smaller volumes of the ipsilateral subiculum (SUB), contralateral SUB, and ipsilateral cortical nucleus of AMG than patients with RTLE-HS. Patients with RTLE-HS had reduced ipsilateral cornu ammonis (CA) 2/3 and contralateral cortico-amygdaloid transition area (CAT) volumes. The relationship between clinical variables and subregions was different based on the lateralization of the seizure focus. Focal to bilateral tonic-clonic seizures (FTBTCS) was associated with contralateral and ipsilateral side subregions only in LTLE-HS. The abdominal FAS was associated with the volume reduction of AMG subregions only in LTLE-HS, but the volume reduction was less than in patients without FAS. Conclusions: The results indicate that unilateral TLE-HS is a bilateral disease that shows different laterality-dependent characteristics based on the subfield analysis of HC and AMG. Subfield volumes of HC and AMG were associated with clinical variables, and the more damaged substructures depended on laterality in TLE-HS. These findings support the evidence that LTLE-HS and RTLE-HS are disparate epilepsy entities rather than simply identical syndromes harboring a mesial temporal lesion. In addition, the presence of FAS supports good localization value, and abdominal FAS has a high localization value, especially in patients with LTLE-HS.

Dataset Information

MicroRNA expression profile of the hippocampus in a rat model of temporal lobe epilepsy and miR-34a-targeted neuroprotection against hippocampal neurone cell apoptosis post-status epilepticus.

Background

Methods

Results

Conclusions

Publications

MicroRNA expression profile of the hippocampus in a rat model of temporal lobe epilepsy and miR-34a-targeted neuroprotection against hippocampal neurone cell apoptosis post-status epilepticus.

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