Progesterone-induced agrin expression in astrocytes modulates glia-neuron interactions leading to synapse formation.
Progesterone-induced agrin expression in astrocytes modulates glia-neuron interactions leading to synapse formation.
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星形胶质细胞中黄体酮诱导的集聚蛋白表达调节神经胶质细胞-神经元相互作用，导致突触形成。
DOI：
10.1016/j.neuroscience.2006.05.004
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发表时间：
2006
期刊：
影响因子：
3.3
通讯作者：
Ferreira,A
中科院分区：
文献类型：
--
作者：
Tournell,CE;Bergstrom,RA;Ferreira,A
最近获得的实验证据表明，突触发生是一个三方事件，不仅突触前和突触后神经元，而且神经胶质细胞在其中发挥关键作用。然而，胶质细胞调节中枢神经系统突触形成的分子机制仍然知之甚少。在本研究中，我们分析了星形胶质细胞在培养的大鼠海马神经元突触形成中的作用。在这些实验中，海马神经元在存在或不存在单层星形胶质细胞的情况下进行培养。我们的结果表明，在有星形胶质细胞存在的情况下培养的海马神经元比在无星形胶质细胞的情况下培养的海马神经元形成更多的突触，只有在无血清的条件下才能保持。为了深入了解这种效应背后的潜在分子机制，我们分析了已知的诱导海马神经元突触形成的蛋白质的表达。无血清培养的星形胶质细胞与无血清培养的星形胶质细胞相比，集聚蛋白的表达显著增加。使用氮气混合物的不同成分进行的实验表明，孕酮诱导星形胶质细胞中集聚蛋白的表达。综上所述，这些结果提供了支持星形胶质细胞在中枢神经元突触形成中的作用的证据。此外，他们发现集聚蛋白是这一效应的潜在中介，而星形胶质细胞在突触形成过程中是内分泌和神经系统之间的桥梁。
Experimental evidence recently obtained suggests that synaptogenesis is a tripartite event in which not only pre- and post-synaptic neurons but also glial cells play a key role. However, the molecular mechanisms by which glia modulate the formation of synapses in the CNS remain poorly understood. In the present study, we analyzed the role of astrocytes in synapse formation in cultured hippocampal rat neurons. For these experiments, hippocampal neurons were cultured in the presence or absence of a monolayer of astrocytes. Our results indicated that hippocampal neurons cultured in the presence of astrocytes formed more synapses than the ones cultured in their absence only when kept in N2 serum-free medium. To get insights into the potential molecular mechanisms underlying this effect, we analyzed the expression of proteins known to induce synapse formation in hippocampal neurons. A significant increase in agrin expression was detected in astrocytes cultured in N2 serum-free medium when compared with the ones cultured in serum containing medium. Experiments performed using different components of the N2 mixture indicated that progesterone induced the expression of agrin in astrocytes. Taken collectively, these results provide evidence supporting a role for astrocytes in synapse formation in central neurons. Furthermore, they identified agrin as a potential mediator of this effect, and astrocytes as a bridge between the endocrine and nervous systems during synaptogenesis.