Goritz Christian, Mauch Daniela H, Pfrieger Frank W
Max-Planck/CNRS Group, UPR 2356, Centre de Neurochimie, 5, rue Blaise Pascal, F-67084 Strasbourg, France.
Mol Cell Neurosci. 2005 Jun;29(2):190-201. doi: 10.1016/j.mcn.2005.02.006.
Neurons undergo a complex differentiation process that endows them with the ability to generate electrical signals and to transmit them via synaptic connections. There is increasing evidence that glial cells regulate specific aspects of neuronal differentiation including synapse formation, but the underlying mechanisms are not well understood. Here, we show how glia-derived cholesterol promotes the development of synapses in microcultures of highly purified retinal ganglion cells (RGCs) from postnatal rats. We identify dendrite differentiation as rate limiting step for glia-induced synaptogenesis and we show that this process requires cholesterol. Furthermore, we show that cholesterol enhances directly presynaptic differentiation and that it is essential for continuous synaptogenesis and for the stability of evoked transmitter release. These results reveal new roles of cholesterol in neuronal differentiation and underline the importance of neuron-glia interactions during brain development.
神经元经历一个复杂的分化过程，使它们具备产生电信号并通过突触连接进行传递的能力。越来越多的证据表明，胶质细胞调节神经元分化的特定方面，包括突触形成，但其潜在机制尚未完全了解。在此，我们展示了胶质细胞衍生的胆固醇如何促进新生大鼠高度纯化的视网膜神经节细胞（RGC）微培养物中突触的发育。我们确定树突分化是胶质细胞诱导的突触形成的限速步骤，并表明该过程需要胆固醇。此外，我们表明胆固醇直接增强突触前分化，并且对于持续的突触形成以及诱发递质释放的稳定性至关重要。这些结果揭示了胆固醇在神经元分化中的新作用，并强调了脑发育过程中神经元与胶质细胞相互作用的重要性。
