Jiménez Antonio Jesús, García-Verdugo José Manuel, González César Aliro, Bátiz Luis Federico, Rodríguez-Pérez Luis Manuel, Páez Patricia, Soriano-Navarro Mario, Roales-Buján Ruth, Rivera Patricia, Rodríguez Sara, Rodríguez Esteban Martín, Pérez-Fígares José Manuel
Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga Málaga, Spain.
J Neuropathol Exp Neurol. 2009 Sep;68(9):1006-20. doi: 10.1097/NEN.0b013e3181b44a5a.
Neural stem cells persist after embryonic development in the subventricular zone (SVZ) niche and produce new neural cells during postnatal life; ependymal cells are a key component associated with this neurogenic niche. In the animal model of human hydrocephalus, the hyh mouse, the ependyma of the lateral ventricles is progressively lost during late embryonic and early postnatal life and disappears from most of the ventricular surface throughout its life span. To determine the potential consequences of this loss on the SVZ, we characterized the abnormalities in this neurogenic niche in hyh mice. There was overall disorganization and a marked reduction of proliferative cells in the SVZ of both newborn and adult hyh hydrocephalic mice in vivo; neuroblasts were displaced to the ventricular surface, and their migration through the rostral migratory stream was reduced. The numbers of resident neural progenitor cells in hyh mice were also markedly reduced, but they were capable of proliferating, forming neurospheres, and differentiating into neurons and glia in vitro in a manner indistinguishable from that of wild-type progenitor cells. These findings suggest that the reduction of proliferative activity observed in vivo is not caused by a cell autonomous defect of SVZ progenitors but is a consequence of a reduced number of these cells. Furthermore, the overall tissue disorganization of the SVZ and displacement of neuroblasts imply alterations in the neurogenic niche of postnatal hyh mice.
神经干细胞在胚胎发育后持续存在于脑室下区（SVZ）微环境中，并在出生后产生新的神经细胞；室管膜细胞是与这个神经发生微环境相关的关键组成部分。在人类脑积水的动物模型——hyh小鼠中，侧脑室的室管膜在胚胎后期和出生后早期逐渐丢失，并在其整个生命周期中从大部分脑室表面消失。为了确定这种丢失对SVZ的潜在影响，我们对hyh小鼠这个神经发生微环境中的异常进行了特征描述。在新生和成年的hyh脑积水小鼠体内，SVZ总体结构紊乱，增殖细胞显著减少；神经母细胞被转移到脑室表面，并且它们通过吻侧迁移流的迁移减少。hyh小鼠中驻留神经祖细胞的数量也显著减少，但它们能够增殖，形成神经球，并在体外分化为神经元和神经胶质细胞，其方式与野生型祖细胞没有区别。这些发现表明，在体内观察到的增殖活性降低不是由SVZ祖细胞的细胞自主缺陷引起的，而是这些细胞数量减少的结果。此外，SVZ的整体组织紊乱和神经母细胞的移位意味着出生后hyh小鼠神经发生微环境的改变。
