Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
J Neurosci. 2010 Mar 24;30(12):4508-14. doi: 10.1523/JNEUROSCI.5027-09.2010.
Astrocytes are now distinguished as major regulators of neuronal growth and synaptic development. Recently, they have been identified as key players in the progression of a number of developmental disorders; however, in fragile X syndrome (FXS), the role of astrocytes is not known. Using a coculture design, we found that hippocampal neurons exhibited abnormal dendritic morphology and a decreased number of presynaptic and postsynaptic protein aggregates when they were grown on astrocytes from a fragile X mouse. Moreover, we found that normal astrocytes could prevent the development of abnormal dendrite morphology and preclude the reduction of presynaptic and postsynaptic protein clusters in neurons from a fragile X mouse. These experiments are the first to establish a role for astrocytes in the altered neurobiology of FXS. Our results support the notion that astrocytes contribute to abnormal dendrite morphology and the dysregulated synapse development in FXS.
星形胶质细胞现在被认为是神经元生长和突触发育的主要调节者。最近，它们被确定为许多发育障碍进展的关键因素；然而，在脆性 X 综合征 (FXS) 中，星形胶质细胞的作用尚不清楚。通过共培养设计，我们发现当海马神经元在来自脆性 X 小鼠的星形胶质细胞上生长时，它们表现出异常的树突形态和减少的突触前和突触后蛋白聚集体。此外，我们发现正常的星形胶质细胞可以防止脆性 X 小鼠神经元中异常树突形态的发展，并防止突触前和突触后蛋白簇的减少。这些实验首次确立了星形胶质细胞在 FXS 改变的神经生物学中的作用。我们的结果支持这样一种观点，即星形胶质细胞有助于 FXS 中异常树突形态和失调的突触发育。
