Heterogeneity in Synaptogenic Profile of Astrocytes from Different Brain Regions
Heterogeneity in Synaptogenic Profile of Astrocytes from Different Brain Regions
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DOI：
10.1007/s12035-016-0343-z
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发表时间：
2018-01-01
影响因子：
5.1
通讯作者：
Alcantara Gomes, Flavia Carvalho
中科院分区：
文献类型：
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作者：
Buosi, Andrea Schmidt;Matias, Isadora;Alcantara Gomes, Flavia Carvalho
星形胶质细胞是中枢神经系统（CNS）中最丰富的神经胶质细胞，由异质性细胞群组成。然而，这种异质性如何影响它们在大脑内稳态中的功能以及对损伤和疾病的反应在很大程度上仍然是未知的。近年来，星形胶质细胞被认为是突触形成和成熟的重要调节因子。在这里，我们分析了来自中枢神经系统不同区域的星形胶质细胞的突触发生特性。评价了来自大脑皮层、海马、中脑和小脑的星形胶质细胞的条件培养基（星形胶质细胞条件培养基（ACM））在突触形成中的作用。通过定量突触前和突触后蛋白、突触体蛋白和突触后密度蛋白95（PSD-95）来分析突触形成。四个脑区的ACM均能显著增加同一脑区和不同脑区神经元上突触素/PSD-95斑点的数量。根据ACM蛋白浓度的不同，观察到不同区域之间星形胶质细胞突触发生潜力的差异。因此，当ACM浓度较低时，小脑星形胶质细胞具有较高的突触发生作用。此外，异型共培养实验表明，大脑皮层和中脑的神经元同样对ACM反应，表明突触效应的差异不像是神经元自主的。通过qPCR分析由来自不同脑区域的星形胶质细胞分泌的突触发生分子的表达谱。磷脂酰肌醇蛋白聚糖4和6、hevin以及分泌的酸性和富含半胱氨酸的蛋白质（glypicans）的基因表达在来自不同脑区的星形胶质细胞之间存在很大差异。此外，hevin蛋白的体内分析证实了这种差异。这些发现突出了星形胶质细胞的异质性，并表明它们的突触发生潜力在每个脑区域可能是不同的，主要是由于不同的基因表达谱。
Astrocytes, the most abundant glial cells in the central nervous system (CNS), comprise a heterogeneous population of cells. However, how this heterogeneity impacts their function within brain homeostasis and response to injury and disease is still largely unknown. Recently, astrocytes have been recognized as important regulators of synapse formation and maturation. Here, we analyzed the synaptogenic property of astrocytes from different regions of the CNS. The effect of conditioned medium derived from astrocytes (astrocyte-conditioned medium (ACM)) from cerebral cortex, hippocampus, midbrain and cerebellum, in synapse formation, was evaluated. Synapse formation was analyzed by quantification of pre- and postsynaptic proteins, synaptophysin, and postsynaptic density protein 95 (PSD-95). ACM from the four regions increased significantly the number of synaptophysin/PSD-95 puncta on neurons from the same and different brain regions. Differences on astrocytic synaptogenic potential between the regions were observed according to ACM protein concentration. Thus, cerebellar astrocytes have higher synaptogenic effect when ACM is less concentrated. Also, heterotypical co-culture assays revealed that neurons from cerebral cortex and midbrain equally respond to ACM, indicating that differences in synapse effect are unlike to be neuron-autonomous. The expression profile of the synaptogenic molecules secreted by astrocytes from distinct brain regions was analyzed by qPCR. Gene expression of glypicans 4 and 6, hevin, and secreted protein-acidic and rich in cysteine (SPARC) greatly varies between astrocytes from different brain regions. Furthermore, in vivo analysis of hevin protein confirmed that variance. These findings highlight the heterogeneity of astrocytes and suggest that their synaptogenic potential may be different in each brain region, mainly due to distinct gene expression profiles.