Liu Rui, Wang Zhe, Gou Lin, Xu Hanpeng
Department of Physiotherapy and Rehabilitation, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
Unit of Spinal Surgery, Department of Orthopedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Mol Med Rep. 2015 Aug;12(2):2598-606. doi: 10.3892/mmr.2015.3702. Epub 2015 Apr 29.
Astrocytes are the most heterogeneous and predominant glial cell type in the central nervous system. However, the functional significance of this heterogeneity remains to be elucidated. Following injury, damaged astrocytes inhibit axonal regeneration in vivo and in vitro. Cultured primary astrocytes are commonly considered good supportive substrates for neuron attachment and axon regeneration. However, it is not known whether different populations of cells in the heterogeneous astrocyte culture affect neuron behavior in the same way. In the present study, the effect of astrocyte heterogeneity on neuronal attachment and neurite outgrowth was examined using an in vitro and in vivo coculture system. In vitro, neonatal cortical astrocytes were co-cultured with purified dorsal root ganglia (DRG) neurons and astrocyte growth morphology, neuron attachment and neurite growth were evaluated. The results demonstrated that the heterogeneous astrocyte cells showed two different types of growth pattern, typical and atypical. Typical astrocytes were supportive to neuron attachment and neurite growth, which was consistent with previous studies, whereas atypical astrocytes inhibited neuron attachment and neurite growth. These inhibitory astrocytes exhibited a special growth pattern with various shapes and sizes, a high cell density, few oligodendrocytes on the top layer and occupied a smaller growth area compared with typical astrocytes. Neurites extended freely on typical supportive astrocyte populations, however, moved away when they reached atypical astrocyte growth pattern. Neurons growing on the atypical astrocyte pattern demonstrated minimal neurite outgrowth and these neurites had a dystrophic appearance, however, neuronal survival was unaffected. Immunocytochemistry studies demonstrated that these atypical inhibitory astrocytes were glial fibrillary acidic protein (GFAP) positive cells. The existence of inhibitory astrocyte subpopulations in normal astrocytes reflects the complexity of the function of astrocyte populations. In vivo, DRG neurons in grey matter did not show neurite growth, while DRG neurons survived and showed robust axon outgrowth along the corpus callosum. In conclusion, further studies on this new type of inhibitory astrocyte subpopulation may deepen our understanding of the complex biology of astrocytes.
星形胶质细胞是中枢神经系统中最具异质性且占主导地位的神经胶质细胞类型。然而，这种异质性的功能意义仍有待阐明。损伤后，受损的星形胶质细胞在体内和体外均会抑制轴突再生。培养的原代星形胶质细胞通常被认为是神经元附着和轴突再生的良好支持性底物。然而，尚不清楚异质性星形胶质细胞培养物中的不同细胞群体是否以相同方式影响神经元行为。在本研究中，使用体外和体内共培养系统研究了星形胶质细胞异质性对神经元附着和神经突生长的影响。在体外，将新生皮质星形胶质细胞与纯化的背根神经节（DRG）神经元共培养，并评估星形胶质细胞的生长形态、神经元附着和神经突生长。结果表明，异质性星形胶质细胞呈现出两种不同的生长模式，即典型模式和非典型模式。典型星形胶质细胞对神经元附着和神经突生长具有支持作用，这与先前的研究一致，而非典型星形胶质细胞则抑制神经元附着和神经突生长。这些具有抑制作用的星形胶质细胞呈现出特殊的生长模式，具有各种形状和大小，细胞密度高，顶层少突胶质细胞少，与典型星形胶质细胞相比生长面积较小。神经突在典型的支持性星形胶质细胞群体上自由延伸，但当它们到达非典型星形胶质细胞生长模式区域时会离开。在非典型星形胶质细胞模式上生长的神经元神经突生长极少，且这些神经突呈现营养不良的外观，不过神经元的存活未受影响。免疫细胞化学研究表明，这些非典型的具有抑制作用的星形胶质细胞是胶质纤维酸性蛋白（GFAP）阳性细胞。正常星形胶质细胞中存在具有抑制作用的星形胶质细胞亚群反映了星形胶质细胞群体功能的复杂性。在体内，灰质中的DRG神经元未显示神经突生长，而DRG神经元存活并沿胼胝体显示出强劲的轴突生长。总之，对这种新型具有抑制作用的星形胶质细胞亚群的进一步研究可能会加深我们对星形胶质细胞复杂生物学特性的理解。
