Effects of MiR-196a on Neuronal Morphology in vitro and in vivo

摘要

MicroRNAs (miRNAs) non-protein-coding RNA molecules play an important role at different stages of neuronal development including growth cone organization spine formation and neurite outgrowth Our previous data indicates that a specific miRNA miR-196a ameliorates phenotypes of Huntington’s disease (HD) However the protective mechanism of miR-196a in HD is still unknown Maintaining the neuronal morphology is one of the potential neuroprotective mechanisms We hypothesize miR-196a might promote neuronal morphology and regulate resulting phenotypes In this study we discovered miR-196a enhanced neurite outgrowth in both neuroblastoma cell and transgenic mouse models In addition miR-196a promoted anterograde transport Furthermore miR-196a transgenic mice not only expressed stronger long-term potentiation in hippocampal CA1 but also appeared more advantageous functions of learning and memory than the non-transgenic mice To understand the mechanisms we used bioinformatics and identified a target gene Ran-binding protein 10 (Ranbp10) which is related to microtubule equilibrium in platelet We discovered that miR-196a suppressed the expression of Ranbp10 and promoted beta-tubulin organization On the contrary overexpression of Ranbp10 impaired the expression profiling of beta-tubulin and decreased neurite outgrowth and retrograde transport Furthermore we generated Ranbp10 transgenic mice and discovered the suppression of neurite outgrowth in the mice In summary our results suggest miR-196a improves neurite outgrowth through alteration of Ranbp10 Therefore we anticipate this study will provide a potential therapeutic direction for HD

獎項日期	2016 8月 4
原文	English
監督員	Shang-Hsun Yang (Supervisor)