Laboratory of Neuronal Plasticity and Neurorepair, Institute for Neuroscience of Castilla y León, Universidad de Salamanca, Salamanca, Spain.
Cell Transplant. 2011;20(8):1179-92. doi: 10.3727/096368910X552826. Epub 2011 Feb 3.
Many studies have reported the contribution of bone marrow-derived cells (BMDC) to the CNS, raising the possibility of using them as a new source to repair damaged brain tissue or restore neuronal function. This process has mainly been investigated in the cerebellum, in which a degenerative microenvironment has been suggested to be responsible for its modulation. The present study further analyzes the contribution of BMDC to different neural types in other adult brain areas, under both physiological and neurodegenerative conditions, together with the mechanisms of plasticity involved. We grafted genetically marked green fluorescent protein/Cre bone marrow in irradiated recipients: a) the PCD (Purkinje Cell Degeneration) mutant mice, suffering a degeneration of specific neuronal populations at different ages, and b) their corresponding healthy controls. These mice carried the conditional lacZ reporter gene to allow the identification of cell fusion events. Our results demonstrate that BMDC mainly generate microglial cells, although to a lesser extent a clear formation of neuronal types also exists. This neuronal recruitment was not increased by the neurodegenerative processes occurring in PCD mice, where BMDC did not contribute to rescuing the degenerated neuronal populations either. However, an increase in the number of bone marrow-derived microglia was found along the life span in both experimental groups. Six weeks after transplantation more bone marrow-derived microglial cells were observed in the olfactory bulb of the PCD mice compared to the control animals, where the degeneration of mitral cells was in process. In contrast, this difference was not observed in the cerebellum, where Purkinje cell degeneration had been completed. These findings demonstrated that the degree of neurodegenerative environment can foster the recruitment of neural elements derived from bone marrow, but also provide the first evidence that BMDC can contribute simultaneously to different encephalic areas through different mechanisms of plasticity: cell fusion for Purkinje cells and differentiation for olfactory bulb interneurons.
许多研究报告了骨髓源性细胞 (BMDC) 对中枢神经系统的贡献，这提高了利用它们作为修复受损脑组织或恢复神经元功能的新来源的可能性。 该过程主要在小脑中进行了研究，据推测其退化微环境负责对其进行调节。 本研究进一步分析了 BMDC 在生理和神经退行性条件下对其他成年脑区不同神经类型的贡献，以及涉及的可塑性机制。 我们将遗传标记的绿色荧光蛋白/ Cre 骨髓移植到照射受体中：a）PCD（浦肯野细胞退化）突变小鼠，其在不同年龄患有特定神经元群体的退化，和 b）其相应的健康对照。 这些小鼠携带条件性 lacZ 报告基因，以允许鉴定细胞融合事件。 我们的结果表明，BMDC 主要产生小胶质细胞，尽管程度较小，但也存在明显的神经元类型形成。 这种神经元募集没有因 PCD 小鼠中发生的神经退行性过程而增加，BMDC 也没有有助于挽救退化的神经元群体。 然而，在两个实验组的整个生命过程中，骨髓源性小胶质细胞的数量均增加。 与对照组动物相比，在 PCD 小鼠的嗅球中观察到移植后 6 周时更多的骨髓源性小胶质细胞，其中有 Mitral 细胞的退化过程。 相反，在小脑中没有观察到这种差异，其中浦肯野细胞的退化已经完成。 这些发现表明神经退行性环境的程度可以促进源自骨髓的神经元素的募集，但也首次证明 BMDC 可以通过不同的可塑性机制同时对不同的脑区做出贡献：细胞融合用于浦肯野细胞，分化用于嗅球中间神经元。
