Abstract
BackgroundRecurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNAs have been revealed as players in the progression of numerous diseases including cancer and Alzheimer’s disease. Particularly, microRNA has been found linked to seizure-induced neuronal death. In this study, a rat model of recurrent convulsions induced by flurothyl treatments was utilised to assess the alterations of microRNA expressions in hippocampus tissues. We also applied an in vitro model in which primary astrocytes were exposed to kainic acid to verify the targets of miR-34b-5p identified in the animal model.ResultsWe discovered that miR-34b-5p, a member of the miR-34 family, increased significantly in flurothyl-treated rat hippocampus tissue. More surprisingly, this upregulation occurred concurrently with accumulating astrocyte apoptosis, indicating the involvement of miR-34b-5p in seizures caused astrocyte apoptosis. Results from the in vitro experiments further demonstrated that miR-34b-5p directly targeted Bcl-2 mRNA, translationally repressed Bcl-2 protein, and thus modulated cell apoptosis by influencing Bcl-2, Bax, and Caspase-3.ConclusionOur findings prove microRNAs play a role in mediating recurrent convulsions-induced astrocyte death and further indicate that miR-34b-5p could acts as a regulator for astrocyte apoptosis induced by recurrent seizures.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-016-0291-6) contains supplementary material, which is available to authorized users.
Highlights
Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage
We discovered that one subtype of miR-34b—miR34b-5p—mediated astrocyte apoptosis caused by recurrent flurothyl-induced seizures in the way in which they directly targeted Bcl-2
In order to study the role of microRNAs in mediating brain damage related to recurrent convulsions, we used a rat model of recurrent convulsions in which we exposed rats to flurothyl for six consecutive days
Summary
Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNA has been found linked to seizure-induced neuronal death. A rat model of recurrent convulsions induced by flurothyl treatments was utilised to assess the alterations of microRNA expressions in hippocampus tissues. We applied an in vitro model in which primary astrocytes were exposed to kainic acid to verify the targets of miR-34b-5p identified in the animal model. Status epilepticus (SE), a prolonged seizure, has a higher prevalence in children than adults. Recurrent convulsions associated with SE during neonatal development cause irreversible brain damage. Exploring the mechanisms and treatments of recurrent convulsions has become an emerging primary focus in clinical research.
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