Abstract
BackgroundThe aim of this study is to explore the effect of microRNA-103a (miR-103a) on astrocytes activation and hippocampal neuron injury in epilepsy rats by targeting brain-derived neurotrophic factor (BDNF).MethodsThe epilepsy rat model was induced by intraperitoneal injection of lithium chloride-pilocarpine. Successful modeled rats were intralateroventricularly microinjected with miR-103a inhibitors, inhibitors negative control (NC), siRNA-NC and BDNF-siRNA, respectively. The RT-qPCR and western blot analysis were used to detect the expression of miR-103a, BDNF and glial fibrillary acidic protein (GFAP) in hippocampus tissues of rats. TUNEL staining was used to detect the apoptosis of hippocampal neurons. The RT-PCR and ELISA was used to detect the levels of TNF-α and IL-6 in hippocampal tissues and in serum, respectively.ResultsIncreased expression of miR-103a, GFAP, and number of apoptotic neurons, decreased expression of BDNF and number of surviving neurons were found in hippocampus tissues of epilepsy rats. After miR-103a inhibitors interfered with epilepsy rats, there showed decreased expression of miR-103a and GFAP, increased expression of BDNF and decreased number of apoptotic neuron as well as increased number of surviving neurons. Compared with miR-103a inhibitors alone, epilepsy rats treated with BDNF-siRNA combined with miR-103a inhibitors significantly increased expression of GFAP in hippocampal tissues of epilepsy rats, increased number of apoptotic neurons and significantly decreased the number of surviving neurons.ConclusionOur study provides evidence that the inhibition of miR-103a can inhibit the activation of astrocytes in hippocampus tissues and improve the pathological injury of neurons of epilepsy rats by regulating BDNF gene.
Highlights
The aim of this study is to explore the effect of microRNA-103a on astrocytes activation and hippocampal neuron injury in epilepsy rats by targeting brain-derived neurotrophic factor (BDNF)
Our study provides evidence that the inhibition of miR-103a can inhibit the activation of astrocytes in hippocampus tissues and improve the pathological injury of neurons of epilepsy rats by regulating BDNF gene
According to the body weight, the rats were randomly assigned into six groups, with 15 rats in each group, namely the sham group, the EP group, the inhibitors negative control (NC) group, miR-103a inhibitors + siRNA-NC group and miR-103a inhibitors + BDNF-siRNA group. miR-103a inhibitors, inhibitors NC, BDNF-siRNA and siRNA-NC plasmids were all purchased from Shanghai GenePharma Co., Ltd (Shanghai, China)
Summary
The aim of this study is to explore the effect of microRNA-103a (miR-103a) on astrocytes activation and hippocampal neuron injury in epilepsy rats by targeting brain-derived neurotrophic factor (BDNF). Evidence has shown that inhibition of miR-103 can up-regulate NCX1 gene, reduce the volume of cerebral infarction after stroke, and improve the neurological deficit after stroke [20] These results suggest that the upregulation of miR-103 may play an important role in the regulation of gene expression in the central nervous system. This study is performed to explore the effects of miR-103a on astrocytes activation and hippocampal neuron injury in epilepsy rats by binding to BDNF
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