神经元和星形胶质细胞特异性miRNA对神经网络发育和功能的调控机制

Existing evidence suggests that synaptogenesis can be facilitated by astrocytes. The interaction between astrocytes and neurons is essential for neural network formation and function. MicroRNA is a highly conservative 17-25nt non-coding RNA, which regulate gene expression at post transcriptional levels. Some miRNAs have been shown to modulate nervous system function with unknown mechanisms. Using astrocyte-specific dicer knockout mice, our previous work had demonstrated that astrocyte-specific miRNA pathways participate in prevention of neural excitotoxicity. In addition, we found that in the forebrain region of these mice, synaptic integety was also affected. In this proposal, we will use astrocyte and neuron-specific dicer knockout mice, and combining immunohistochemical and electrophysiological analyses to study how astrocyte-specific and neuron-specific miRNA pathways affect the morphology of neuron, synaptogenesis and maintenance of synaptic function in vivo and in vitro.Then rely on miRNA expression profiling and PI-Deconvolution strategy, we will find specific miRNA species from neurons and/or astrocytes, which regulate neuronal morphogenesis, synapse formation and function. By means of this research; we could identify specific key miRNAs regulate the development and function of brain neural circuits in a spatiotemporal specific manner, which might provide new insight in the area of synaptic biology and poentially some new targets for drug development to treat neurological disorders, which often reflect deficits in synaptic function.

MicroRNA(miRNA)是基因转录后水平上的重要调控因子，可以影响神经发生和功能。星形胶质细胞能与神经元相互作用，促进突触的发生。我们在Dicer条件敲除小鼠中的工作显示:星形胶质细胞特异的miRNA参与了这一过程，但其对神经系统的精细调控机制仍然未知。另外，神经元特异的miRNA如何参与调控，有哪些神经细胞特异的miRNA参与调控，这些问题仍然有待阐明。我们将用两种Dicer条件敲除小鼠，从体内、体外两个方面，分别研究神经元和星形胶质细胞各自特异的miRNAs的调控作用，结合miRNA表达谱分析和 PI-Deconvolution分类策略，在体外筛选出起重要调节作用的miRNA，并在体内验证，而后通过Tet-on系统进行后续研究。本项目的完成将阐明miRNA调控神经环路形态发生和功能维持的时空关系，筛选出在其中起关键作用的神经元和星形胶质细胞来源的miRNA。

MicroRNA(miRNA)是基因转录后水平上的重要调控因子，可以影响神经发生和功能。星形胶质细胞能与神经元相互作用，促进突触的发生。我们在Dicer条件敲除小鼠中的工作显示:星形胶质细胞特异的miRNA参与了这一过程，但其对神经系统的精细调控机制仍然未知。另外，神经元特异的miRNA如何参与调控，有哪些神经细胞特异的miRNA参与调控，这些问题仍然有待阐明。我们将用两种Dicer条件敲除小鼠，从体内、体外两个方面，分别研究神经元和星形胶质细胞各自特异的miRNAs的调控作用，结合miRNA表达谱分析和 PI-Deconvolution分类策略，在体外筛选出起重要调节作用的miRNA，并在体内验证，而后通过Tet-on系统进行后续研究。我们重点关注已经筛选获得的mir-9和mir-137。深入研究其有关功能，将阐明miRNA调控神经环路形态发生和功能维持的时空关系，鉴定出在其中起关键作用的神经元和星形胶质细胞来源的miRNA。