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Silencing miR-20a-5p inhibits axonal growth and neuronal branching and prevents epileptogenesis through RGMa-RhoA-mediated synaptic plasticity.
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-08-10 , DOI: 10.1111/jcmm.15677
Yanyan Feng 1 , Chaojun Duan 2 , Zhaohui Luo 1 , Wenbiao Xiao 1 , Fafa Tian 1
Affiliation  

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.

中文翻译:

沉默miR-20a-5p可抑制轴突生长和神经元分支,并通过RGMa-RhoA介导的突触可塑性阻止癫痫发生。

癫痫发生是一个潜在的过程。苔藓纤维发芽(MFS)和突触可塑性促进癫痫发生。排斥性指导分子a(RGMa)的过表达通过抑制MFS防止癫痫发生。然而,尚未阐明RGMa调控癫痫发生过程的其他方面。我们研究了RGMa在癫痫发生过程中是否可以被microRNA调控并调节RhoA。使用microRNA数据库,我们选择了四个miRNA作为潜在候选对象。我们进一步通过实验确认了miR-20a-5p作为RGMa上游调节剂。然后,在体外,通过操纵miR-20a-5p和RGMa,我们研究了miR-20a-5p,RGMa和RhoA之间的调节关系,以及该途径对神经元形态的影响。最后,在癫痫动物模型中 我们确定了miR-20a-5p-RGMa-RhoA途径是否影响MFS和突触可塑性,然后改变癫痫发生。我们的结果表明,miR-20a-5p在体外调节RGMa,而RGMa调节RhoA。此外,在原代海马神经元中,miR-20a-5p-RGMa-RhoA途径调节轴突生长和神经元分支。在PTZ诱发的癫痫模型中,沉默miR-20a-5p通过RGMa-RhoA介导的突触可塑性阻止了癫痫发生,但并未改变MFS。总体而言,我们得出的结论是,在PTZ诱导的癫痫模型中,通过RGMa-RhoA介导的突触可塑性,沉默miR-20a-5p抑制轴突生长和神经元分支,并防止癫痫发生,从而提供了预防癫痫发生的可能策略。我们的结果表明,miR-20a-5p在体外调节RGMa,而RGMa调节RhoA。此外,在原代海马神经元中,miR-20a-5p-RGMa-RhoA途径调节轴突生长和神经元分支。在PTZ诱发的癫痫模型中,沉默miR-20a-5p通过RGMa-RhoA介导的突触可塑性阻止了癫痫发生,但并未改变MFS。总体而言,我们得出的结论是,在PTZ诱导的癫痫模型中,通过RGMa-RhoA介导的突触可塑性,沉默miR-20a-5p抑制轴突生长和神经元分支,并防止癫痫发生,从而提供了预防癫痫发生的可能策略。我们的结果表明,miR-20a-5p在体外调节RGMa,而RGMa调节RhoA。此外,在原代海马神经元中,miR-20a-5p-RGMa-RhoA途径调节轴突生长和神经元分支。在PTZ诱发的癫痫模型中,沉默miR-20a-5p通过RGMa-RhoA介导的突触可塑性阻止了癫痫发生,但并未改变MFS。总体而言,我们得出的结论是,在PTZ诱导的癫痫模型中,通过RGMa-RhoA介导的突触可塑性,沉默miR-20a-5p抑制轴突生长和神经元分支,并防止癫痫发生,从而提供了预防癫痫发生的可能策略。在PTZ诱发的癫痫模型中,沉默miR-20a-5p通过RGMa-RhoA介导的突触可塑性阻止了癫痫发生,但并未改变MFS。总的来说,我们得出的结论是,在PTZ诱导的癫痫模型中,通过RGMa-RhoA介导的突触可塑性,沉默miR-20a-5p抑制轴突生长和神经元分支,并防止癫痫发生,从而提供了预防癫痫发生的可能策略。在PTZ诱发的癫痫模型中,沉默miR-20a-5p通过RGMa-RhoA介导的突触可塑性阻止了癫痫发生,但并未改变MFS。总的来说,我们得出的结论是,在PTZ诱导的癫痫模型中,通过RGMa-RhoA介导的突触可塑性,沉默miR-20a-5p抑制轴突生长和神经元分支,并防止癫痫发生,从而提供了预防癫痫发生的可能策略。
更新日期:2020-09-28
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