| Summary: | 博士 === 國立陽明大學 === 生命科學系暨基因體科學研究所 === 101 === The translation of dendritic microtubule-associated protein 1B (MAP1B) is exaggerated upon group I mGluR activation leading to AMPA receptor (AMPAR) endocytosis and consequent long-term depression. Studies of mice deficient in FMRP have suggested the repression of MAP1B protein expression by FMRP in postnatal brains. Several miRNAs are implicated in the translational repression of neuronal genes and the regulation of synaptic plasticity. However, it remains unclear whether miRNAs involved in the regulation of MAP1B translation in mature dendrites.
In this thesis, I have identified miR-146a-5p that targets the 3′ UTR of MAP1B mRNA in a FMRP-independent manner. Inhibition of the endogenous miR-146a-5p in mouse cultured hippocampal neurons triggers an increase of the dendritic MAP1B protein as well as the internalization of AMPARs, resulting in a decline in synaptic transmission. Conversely, enforced expression of miR-146a-5p inhibits MAP1B translation and attenuates group I mGluR-induced AMPAR endocytosis. Moreover, siRNA-mediated knockdown of MAP1B recovers the impairment of synaptic transmission caused by inhibition of miR-146a-5p. These results reveal that miR-146a-5p modulates the synaptic plasticity via repression of MAP1B protein synthesis. My findings also provide a possible scenario for pathogenesis of Rett syndrome in which the biogenesis of miR-146a-5p is downregulated.
Additionally, I have investigated another topic about miRNAs that are involved in the left/right asymmetry of cerebrums. The details are described in the section of appendices.
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