Department of Neuroscience, University of Pennsylvania School of Medicine, 215 Stemmler Hall, Philadelphia, PA 19104-6074, USA.
Mol Cell Neurosci. 2010 Jan;43(1):136-45. doi: 10.1016/j.mcn.2009.10.004. Epub 2009 Oct 20.
Astrocytes modulate the formation and function of glutamatergic synapses in the CNS, but whether astrocytes modulate GABAergic synaptogenesis is unknown. We demonstrate that media conditioned by astrocytes, but not other cells, enhanced GABAergic but not glutamatergic axon length and branching, and increased the number and density of presynaptically active GABAergic synapses in dissociated hippocampal cultures. Candidate mechanisms and factors, such as activity, neurotrophins, and cholesterol were excluded as mediating these effects. While thrombospondins secreted by astrocytes are necessary and sufficient to increase hippocampal glutamatergic synaptogenesis, they do not mediate astrocyte effects on GABAergic synaptogenesis. We show that the factors in astrocyte conditioned media that selectively affect GABAergic neurons are proteins. Taken together, our results show that astrocytes increase glutamatergic and GABAergic synaptogenesis via different mechanisms and release one or more proteins with the novel functions of increasing GABAergic axon length, branching and synaptogenesis.
星形胶质细胞调节中枢神经系统中谷氨酸能突触的形成和功能，但星形胶质细胞是否调节 GABA 能突触发生尚不清楚。我们证明，星形胶质细胞而不是其他细胞分泌的条件培养基增强了 GABA 能但不是谷氨酸能轴突的长度和分支，并增加了分离海马培养物中具有突触前活性的 GABA 能突触的数量和密度。候选机制和因素，如活性、神经营养因子和胆固醇被排除作为介导这些效应的因素。虽然星形胶质细胞分泌的血栓素原是增加海马谷氨酸能突触发生所必需和充分的，但它们不介导星形胶质细胞对 GABA 能突触发生的影响。我们表明，星形胶质细胞条件培养基中选择性影响 GABA 能神经元的因子是蛋白质。总之，我们的结果表明，星形胶质细胞通过不同的机制增加谷氨酸能和 GABA 能突触发生，并释放一种或多种具有增加 GABA 能轴突长度、分支和突触发生的新功能的蛋白质。
