Silencing of circIgf1r plays a protective role in neuronal injury via regulating astrocyte polarization during epilepsy
| Autor: | Biwen Peng, Song Han, Xiaohua He, Tao-Xiang Chen, Guang-Tong Jiang, Lin Shao, Xin Dong, Chunjiang He, Shuo Kong, Xing-Liang Yang, Jing-Jing Cheng, Meng-Liu Zeng, Jun Yin, Wanhong Liu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Neurogenesis Status epilepticus Biology Biochemistry Receptor IGF Type 1 03 medical and health sciences Epilepsy Mice 0302 clinical medicine Downregulation and upregulation Genetics medicine Gene silencing Animals Gene Silencing Molecular Biology Cells Cultured Neurons Autophagy RNA Circular medicine.disease Phenotype Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure nervous system Astrocytes Neuron medicine.symptom Neuroscience 030217 neurology & neurosurgery Biotechnology Astrocyte |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 35(2) |
| ISSN: | 1530-6860 |
| Popis: | Epilepsy is a common brain disorder, repeated seizures of epilepsy may lead to a series of brain pathological changes such as neuronal or glial damage. However, whether circular RNAs are involved in neuronal injury during epilepsy is not fully understood. Here, we screened circIgf1r in the status epilepticus model through circRNA sequencing, and found that it was upregulated after the status epilepticus model through QPCR analysis. Astrocytes polarizing toward neurotoxic A1 phenotype and neurons loss were observed after status epilepticus. Through injecting circIgf1r siRNA into the lateral ventricle, it was found that knocking down circIgf1r in vivo would induce the polarization of astrocytes to phenotype A2 and reduce neuronal loss. The results in vitro further confirmed that inhibiting the expression of circIgf1r in astrocytes could protect neurons by converting reactive astrocytes from A1 to the protective A2. In addition, knocking down circIgf1r in astrocytes could functionally promote astrocyte autophagy and relieve the destruction of 4-AP-induced autophagy flux. In terms of mechanism, circIgf1r promoted the polarization of astrocytes to phenotype A1 by inhibiting autophagy. Taken together, our results reveal circIgf1r may serve as a potential target for the prevention and treatment of neuron damage after epilepsy. |
| Databáze: | OpenAIRE |
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