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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\u201020a\u20105p as a RGMa upstream regulator. Then, in vitro, by manipulating miR\u201020a\u20105p and RGMa, we investigated the regulatory relationship between miR\u201020a\u20105p, RGMa and RhoA, and the effects of this pathway on neuronal morphology. Finally, in the epilepsy animal model, we determined whether the miR\u201020a\u20105p\u2010RGMa\u2010RhoA pathway influenced MFS and synaptic plasticity and then modified epileptogenesis. Our results showed that miR\u201020a\u20105p regulated RGMa and that RGMa regulated RhoA in vitro. Furthermore, in primary hippocampal neurons, the miR\u201020a\u20105p\u2010RGMa\u2010RhoA pathway regulated axonal growth and neuronal branching; in the PTZ\u2010induced epilepsy model, silencing miR\u201020a\u20105p prevented epileptogenesis through RGMa\u2010RhoA\u2010mediated synaptic plasticity but did not change MFS. Overall, we concluded that silencing miR\u201020a\u20105p inhibits axonal growth and neuronal branching and prevents epileptogenesis through RGMa\u2010RhoA\u2010mediated synaptic plasticity in the PTZ\u2010induced epilepsy model, thereby providing a possible strategy to prevent epileptogenesis.<\/jats:p>","DOI":"10.1111\/jcmm.15677","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T01:15:40Z","timestamp":1597108540000},"page":"10573-10588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Silencing miR\u201020a\u20105p inhibits axonal growth and neuronal branching and prevents epileptogenesis through RGMa\u2010RhoA\u2010mediated synaptic plasticity"],"prefix":"10.1111","volume":"24","author":[{"given":"Yanyan","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University Changsha 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