Astroglial heterogeneity closely reflects the neuronal-defined anatomy of the adult murine CNS
Astroglial heterogeneity closely reflects the neuronal-defined anatomy of the adult murine CNS
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DOI：
10.1017/s1740925x06000202
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
Macklis, Jeffrey D.
中科院分区：
文献类型：
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作者：
Emsley, Jason G.;Macklis, Jeffrey D.
星形胶质细胞是一种形态极其多样的细胞类型，在神经发育和功能中起着至关重要的作用。尽管如此，中枢神经系统的不同区域传统上是由神经元的表型特征和连接来定义的。以一种互补的方式，我们提出的证据表明，成人中枢神经系统的离散区域可以仅根据星形胶质细胞的形态、密度和增殖率来划定。我们使用转基因hGFAP-GFP小鼠，其中成年星形胶质细胞中GFP的强大表达可以使用3D共聚焦显微镜对这种多样化异质细胞群进行详细的形态学表征。通过使用三种互补的方法来标记成人星形胶质细胞（hGFAP-GFP表达，GFAP和S100 β免疫染色），我们发现整个中枢神经系统的星形胶质细胞形态具有显著的多样性，区域刻板阵列，并且可以仅根据该区域内星形胶质细胞的形态来定义离散的解剖区域。其次，我们发现星形胶质细胞的密度在整个中枢神经系统中变化很大，星形胶质细胞的密度甚至有效地描绘了复杂结构的子区域，如丘脑。我们还发现星形胶质细胞的区域密度取决于星形胶质细胞被标记的方式。为了量化和说明星形胶质细胞密度的这些广泛差异，我们生成了中枢神经系统的解剖密度图谱。第三，成人中枢神经系统星形胶质细胞的增殖率或有丝分裂指数也有效地定义了解剖区域。无论使用何种星形胶质细胞标记方法，这些差异都存在。为了补充星形胶质细胞密度图谱，我们制作了成人中枢神经系统的增殖密度图谱。总之，这些研究表明星形胶质细胞的形态、密度和增殖率可以独立地定义成年哺乳动物中枢神经系统的离散细胞结构，并支持星形胶质细胞的区域异质性反映不同类别星形胶质细胞之间重要的分子和功能差异的概念，就像长期接受的神经元群体的异质性一样。
Astroglia comprise an extremely morphologically diverse cell type that have crucial roles in neural development and function. Nonetheless, distinct regions of the CNS have traditionally been defined by the phenotypic characteristics and connectivity of neurons. In a complementary fashion, we present evidence that discrete regions of the adult CNS can be delineated based solely on the morphology, density and proliferation rates of astroglia. We used transgenic hGFAP-GFP mice in which robust expression of GFP in adult astroglia enables detailed morphological characterization of this diversely heterogeneous cell population with 3D confocal microscopy. By using three complementary methods for labeling adult astroglia (hGFAP-GFP expression, and GFAP and S100 beta immunostaining), we find that there is a remarkably diverse, regionally stereotypical array of astroglial morphology throughout the CNS, and that discrete anatomical regions can be defined solely on the morphology of astroglia within that region. Second, we find that the density of astroglia varies dramatically across the CNS, and that astroglial density effectively delineates even the sub-regions of complex structures, such as the thalamus. We also find that regional astroglial density varies depending on how astroglia are labeled. To quantify and illustrate these broad differences in astroglial density, we generated an anatomical density atlas of the CNS. Third, the proliferation rate, or mitotic index, of astroglia in the adult CNS also effectively defines anatomical regions. These differences are present regardless of the astroglia beta-labeling method used. To supplement our atlas of astroglial density we generated an atlas of proliferation density for the adult CNS. Together, these studies demonstrate that the morphology, density and proliferation rate of astroglia can independently define the discrete cytoarchitecture of the adult mammalian CNS, and support the concept that regional astroglial heterogeneity reflects important molecular and functional differences between distinct classes of astroglia, much like the long-accepted heterogeneity of neuronal populations.