Moe Simon M, Taylor Alicia, Robertson Alan P, Van Vactor David, McNeill Elizabeth M
Program in Neuroscience, Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50010, USA.
Department of Biomedical Sciences, Iowa State University, Ames, IA 50010, USA.
Biomolecules. 2025 Sep 18;15(9):1330. doi: 10.3390/biom15091330.
MicroRNAs (miRNAs) have emerged as important biomarkers for complex neurological conditions. Modifications in synaptic morphology characterize several of these disease states, indicating a possible role of miRNA in modulating synaptic formation and plasticity. Within the third-instar larvae of Drosophila melanogaster, we uncovered a functional role for highly human-conserved miR-92 in synaptogenesis of the glutamatergic peripheral nervous system. Loss of miR-92 results in underdeveloped synaptic architecture, coinciding with significantly reduced physiological activity. We demonstrate a novel role for miR-92 glial-specific expression to support synaptic growth function and plasticity. Modifications of miR-92 within glial tissue result in aberrant glial barrier properties, including an increased uptake of external dyes. Within the glia, miR-92 regulates a V-ATPase subunit (Vha55), impairing the glial cells from forming appropriate insulating layers around the nervous system. These modifications may impact how the nervous system adapts to its environment, increasing immature 'ghost bouton' budding and impairing responses to changes in environmental conditions. Our work highlights the importance of glial-specific miR-92 on synaptic development, affecting glial health and function through its downstream target Vha55, and demonstrates a novel mechanism for glia in synaptogenesis and homeostatic plasticity.
微小RNA（miRNA）已成为复杂神经系统疾病的重要生物标志物。突触形态的改变是其中几种疾病状态的特征，这表明miRNA在调节突触形成和可塑性方面可能发挥作用。在黑腹果蝇的三龄幼虫中，我们发现高度保守的人类miR-92在谷氨酸能外周神经系统的突触形成中具有功能作用。miR-92的缺失导致突触结构发育不全，同时生理活性显著降低。我们证明了miR-92在神经胶质细胞特异性表达对支持突触生长功能和可塑性具有新作用。神经胶质组织中miR-92的改变导致异常的神经胶质屏障特性，包括外部染料摄取增加。在神经胶质细胞内，miR-92调节一种V-ATP酶亚基（Vha55），损害神经胶质细胞在神经系统周围形成适当绝缘层的能力。这些改变可能影响神经系统如何适应其环境，增加未成熟“空突触小体”的出芽，并损害对环境条件变化的反应。我们的工作突出了神经胶质细胞特异性miR-92对突触发育的重要性，通过其下游靶点Vha55影响神经胶质细胞的健康和功能，并证明了神经胶质细胞在突触形成和稳态可塑性中的新机制。
