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Characterization of Vimentin-Immunoreactive Astrocytes in the Human Brain.
Frontiers in Neuroanatomy ( IF 2.9 ) Pub Date : 2020-07-30 , DOI: 10.3389/fnana.2020.00031
Liam Anuj O'Leary 1, 2 , Maria Antonietta Davoli 1 , Claudia Belliveau 1, 2 , Arnaud Tanti 1 , Jie Christopher Ma 1 , William Todd Farmer 3 , Gustavo Turecki 1, 2, 4 , Keith Kazuo Murai 3 , Naguib Mechawar 1, 2, 4
Affiliation  

Astrocytes are commonly identified by their expression of the intermediate filament protein glial fibrillary acidic protein (GFAP). GFAP-immunoreactive (GFAP-IR) astrocytes exhibit regional heterogeneity in density and morphology in the mouse brain as well as morphological diversity in the human cortex. However, regional variations in astrocyte distribution and morphology remain to be assessed comprehensively. This was the overarching objective of this postmortem study, which mainly exploited the immunolabeling of vimentin (VIM), an intermediate filament protein expressed by astrocytes and endothelial cells which presents the advantage of more extensively labeling cell structures. We compared the densities of vimentin-immunoreactive (VIM-IR) and GFAP-IR astrocytes in various brain regions (prefrontal and primary visual cortex, caudate nucleus, mediodorsal thalamus) from male individuals having died suddenly in the absence of neurological or psychiatric conditions. The morphometric properties of VIM-IR in these brain regions were also assessed. We found that VIM-IR astrocytes generally express the canonical astrocytic markers Aldh1L1 and GFAP but that VIM-IR astrocytes are less abundant than GFAP-IR astrocytes in all human brain regions, particularly in the thalamus, where VIM-IR cells were nearly absent. About 20% of all VIM-IR astrocytes presented a twin cell morphology, a phenomenon rarely observed for GFAP-IR astrocytes. Furthermore VIM-IR astrocytes in the striatum were often seen to extend numerous parallel processes which seemed to give rise to large VIM-IR fiber bundles projecting over long distances. Moreover, morphometric analyses revealed that VIM-IR astrocytes were more complex than their mouse counterparts in functionally homologous brain regions, as has been previously reported for GFAP-IR astrocytes. Lastly, the density of GFAP-IR astrocytes in gray and white matter were inversely correlated with vascular density, but for VIM-IR astrocytes this was only the case in gray matter, suggesting that gliovascular interactions may especially influence the regional heterogeneity of GFAP-IR astrocytes. Taken together, these findings reveal special features displayed uniquely by human VIM-IR astrocytes and illustrate that astrocytes display important region- and marker-specific differences in the healthy human brain.

中文翻译:

人脑中波形蛋白免疫反应性星形胶质细胞的表征。

星形胶质细胞通常通过其中间丝状蛋白胶质原纤维酸性蛋白(GFAP)的表达来鉴定。GFAP免疫反应性(GFAP-IR)星形胶质细胞在小鼠大脑的密度和形态以及人类皮质的形态多样性方面表现出区域异质性。但是,星形胶质细胞分布和形态的区域差异仍有待全面评估。这是这项验尸研究的首要目标,该研究主要利用波形蛋白(VIM)的免疫标记,波形蛋白是星形胶质细胞和内皮细胞表达的中间丝蛋白,具有更广泛地标记细胞结构的优点。我们比较了波形蛋白免疫反应性(VIM-IR)和GFAP-IR星形胶质细胞在各个大脑区域(前额叶和初级视觉皮层,尾状核,来自雄性个体的mediodorsal丘脑)在没有神经或精神疾病的情况下突然死亡。还评估了这些脑区域中VIM-IR的形态特征。我们发现,VIM-IR星形胶质细胞通常表达规范的星形细胞标记Aldh1L1和GFAP,但在所有人脑区域,特别是在几乎没有VIM-IR细胞的丘脑中,VIM-IR星形胶质细胞不如GFAP-IR星形胶质细胞丰富。所有VIM-IR星形胶质细胞中约有20%呈现双胞胎形态,这种现象很少见于GFAP-IR星形胶质细胞。此外,经常看到纹状体中的VIM-IR星形胶质细胞扩展了许多平行过程,这似乎引起了长距离投射的大型VIM-IR纤维束。此外,形态计量学分析显示,在功能同源的大脑区域中,VIM-IR星形胶质细胞比其小鼠对应物更为复杂,正如先前针对GFAP-IR星形胶质细胞的报道。最后,灰质和白质中GFAP-IR星形胶质细胞的密度与血管密度成反比,但是对于VIM-IR星形胶质细胞,仅在灰质中情况如此,这表明胶质血管相互作用可能特别影响GFAP-IR的区域异质性星形胶质细胞。综上所述,这些发现揭示了人类VIM-IR星形胶质细胞独特显示的特殊功能,并说明了星形胶质细胞在健康的人脑中显示出重要的区域和标记特异性差异。灰白质中GFAP-IR星形胶质细胞的密度与血管密度呈负相关,但对于VIM-IR星形胶质细胞,只有灰质情况,这表明胶质血管相互作用可能特别影响GFAP-IR星形胶质细胞的区域异质性。综上所述,这些发现揭示了人类VIM-IR星形胶质细胞独特显示的特殊功能,并说明了星形胶质细胞在健康的人脑中显示出重要的区域和标记特异性差异。灰白质中GFAP-IR星形胶质细胞的密度与血管密度呈反比关系,但对于VIM-IR星形胶质细胞,仅在灰质中情况如此,这表明胶质血管相互作用可能特别影响GFAP-IR星形胶质细胞的区域异质性。综上所述,这些发现揭示了人类VIM-IR星形胶质细胞独特显示的特殊功能,并说明了星形胶质细胞在健康的人脑中显示出重要的区域和标记特异性差异。
更新日期:2020-07-30
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