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成年内源性神经干细胞在纹状体内神经退行性变过程中的增殖与分化。

Proliferation and differentiation of adult endogenous neural stem cells in response to neurodegenerative process within the striatum.

作者信息

Mazurová Yvona, Rudolf Emil, Látr Ivan, Osterreicher Jan

机构信息

Department of Histology and Embryology, Charles University, Faculty of Medicine, Hradec Králové, Czech Republic.

出版信息

Neurodegener Dis. 2006;3(1-2):12-8. doi: 10.1159/000092087.

Abstract

The ongoing process of neurogenesis in the adult mammalian forebrain suggests the possible capacity for limited self-repair after brain injury. Previously, we have demonstrated that in an animal model of Huntington's disease the neurodegenerative process initiates immediate intensive cell proliferation and differentiation resulting in characteristic enlargement of the subependymal zone (SEZ) of lateral brain ventricles. Now, our interest is focused on the architecture of the neurogenic niche of the SEZ in the identical model, particularly on characteristic features of astrocyte-like cells which are considered to be not only niche cells but also neural stem cells. Our findings prove higher activation of the lateral part of the SEZ (L-SEZ) adjacent to the degenerated striatum compared with the rostral part of the SEZ (R-SEZ). In the activated L-SEZ, niche cells which ensheathe clusters of neural progenitors are of immature astrocytic phenotype because of nestin and vimentin expression (except the expression of glial fibrillary acidic protein). However, the coexpression of all three filaments is not always found. Intermediate filaments also enable us to distinguish the basic shape of astrocytic cells within the SEZ, majority of which resemble protoplasmic rather than fibrillary astrocytes. Furthermore, our results show a wide plasticity of these astrocyte-like cells in immediate response to an extensive pathological process in the brain. These observations are consistent with the fact that adult stem cells undergo different processes in an already mature environment, and therefore can exhibit some specific characteristics unlike the embryonic or fetal neural stem cells.

摘要

成年哺乳动物前脑持续进行的神经发生过程表明,脑损伤后可能具有有限的自我修复能力。此前,我们已经证明,在亨廷顿舞蹈病动物模型中,神经退行性过程会立即引发强烈的细胞增殖和分化,导致侧脑室室管膜下区(SEZ)特征性增大。现在,我们的研究兴趣集中在同一模型中SEZ神经源性微环境的结构上,特别是星形胶质样细胞的特征,这些细胞不仅被认为是微环境细胞,也是神经干细胞。我们的研究结果表明,与SEZ的 Rostral部分(R-SEZ)相比,与退化纹状体相邻的SEZ外侧部分(L-SEZ)的激活程度更高。在激活的L-SEZ中,包裹神经祖细胞簇的微环境细胞由于巢蛋白和波形蛋白的表达(胶质纤维酸性蛋白除外)而具有未成熟星形胶质细胞表型。然而,并非总能发现这三种细丝的共表达。中间丝还使我们能够区分SEZ内星形胶质细胞的基本形状,其中大多数类似于原浆性星形胶质细胞而非纤维性星形胶质细胞。此外,我们的结果显示,这些星形胶质样细胞在对大脑广泛病理过程的即时反应中具有广泛的可塑性。这些观察结果与以下事实一致,即成体干细胞在已经成熟的环境中经历不同的过程,因此可能表现出一些不同于胚胎或胎儿神经干细胞的特定特征。

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