Silencing miR‐20a‐5p inhibits axonal growth and neuronal branching and prevents epileptogenesis through RGMa‐RhoA‐mediated synaptic plasticity
| العنوان: | Silencing miR‐20a‐5p inhibits axonal growth and neuronal branching and prevents epileptogenesis through RGMa‐RhoA‐mediated synaptic plasticity |
|---|---|
| المؤلفون: | Zhaohui Luo, Chaojun Duan, Wenbiao Xiao, Fafa Tian, Yanyan Feng |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, rho GTP-Binding Proteins, RHOA, Regulator, Convulsants, Hippocampal formation, neuronal branching, Epileptogenesis, Hippocampus, axonal growth, Rats, Sprague-Dawley, Random Allocation, 0302 clinical medicine, RNA, Small Interfering, 3' Untranslated Regions, Cells, Cultured, Neurons, repulsive guidance molecule a, Neuronal Plasticity, biology, Chemistry, Repulsive guidance molecule A, Dependovirus, 030220 oncology & carcinogenesis, Molecular Medicine, Original Article, Female, mossy fibre sprouting, Signal Transduction, Genetic Vectors, Nerve Tissue Proteins, GPI-Linked Proteins, 03 medical and health sciences, Seizures, microRNA, Gene silencing, Animals, Gene Silencing, synaptic plasticity, Membrane Proteins, Cell Biology, Original Articles, Axons, Rats, Disease Models, Animal, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, Synaptic plasticity, biology.protein, Pentylenetetrazole, RNA, Neuroscience |
| الوصف: | Epileptogenesis is a potential process. Mossy fibre sprouting (MFS) and synaptic plasticity promote epileptogenesis. Overexpression of repulsive guidance molecule a (RGMa) prevents epileptogenesis by inhibiting MFS. However, other aspects underlying the RGMa regulatory process of epileptogenesis have not been elucidated. We studied whether RGMa could be modulated by microRNAs and regulated RhoA in epileptogenesis. Using microRNA databases, we selected four miRNAs as potential candidates. We further experimentally confirmed miR‐20a‐5p as a RGMa upstream regulator. Then, in vitro, by manipulating miR‐20a‐5p and RGMa, we investigated the regulatory relationship between miR‐20a‐5p, RGMa and RhoA, and the effects of this pathway on neuronal morphology. Finally, in the epilepsy animal model, we determined whether the miR‐20a‐5p‐RGMa‐RhoA pathway influenced MFS and synaptic plasticity and then modified epileptogenesis. Our results showed that miR‐20a‐5p regulated RGMa and that RGMa regulated RhoA in vitro. Furthermore, in primary hippocampal neurons, the miR‐20a‐5p‐RGMa‐RhoA pathway regulated axonal growth and neuronal branching; in the PTZ‐induced epilepsy model, silencing miR‐20a‐5p prevented epileptogenesis through RGMa‐RhoA‐mediated synaptic plasticity but did not change MFS. Overall, we concluded that silencing miR‐20a‐5p inhibits axonal growth and neuronal branching and prevents epileptogenesis through RGMa‐RhoA‐mediated synaptic plasticity in the PTZ‐induced epilepsy model, thereby providing a possible strategy to prevent epileptogenesis. |
| اللغة: | English |
| تدمد: | 1582-4934 1582-1838 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d1236b881da1143ecf297d4a7f8f6e44 http://europepmc.org/articles/PMC7521253 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d1236b881da1143ecf297d4a7f8f6e44 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
|---|