Belzunegui Silvia, Izal-Azcárate Amaya, San Sebastián Waldy, Garrido-Gil Pablo, Vázquez-Claverie Marianne, López Berta, Marcilla Irene, Luquin Ma Rosario
Laboratory of Regenerative Therapy, Department of Neurology, Neuroscience Division, Center for Applied Medical Research, University of Navarra, Avda. Pio XII 55, Pamplona, Spain.
Brain Res. 2008 Jun 27;1217:213-20. doi: 10.1016/j.brainres.2008.04.015. Epub 2008 Apr 16.
Progenitor cells generated in the subventricular zone (SVZ) migrate toward the olfactory bulb (OB), where they differentiate into neurons. Growth factors have been shown to promote neurogenesis in the SVZ/OB-system while dopaminergic lesion exerts an opposite effect. As carotid body (CB) cells express growth factors here we study the impact of intrastriatal CB graft on migration and differentiation of neural progenitor cells in the hemiparkinsonian rat SVZ/OB-system. Bromodeoxyuridine (BrdU) was given to intact, 6-hydroxydopamine (6-OHDA)-lesioned and 6-OHDA-lesioned animals transplanted with vehicle or rat CB cells. The migration of progenitor cells was assessed by the quantification of BrdU-labeled cells in the SVZ/OB-system and the neuronal differentiation by the proportion of newborn neurons in the OB. The graft survival was confirmed by CB cell morphology and their tyrosine hydroxylase expression. Some of these CB cells were stained with BrdU, thus indicating their ability for self-renewal. Grafted glomus cells also expressed brain derived neurotrophic factor (BDNF), glial derived neurotrophic factor (GDNF), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). The migration of neural progenitor cells was significantly decreased in 6-OHDA-lesioned respect to intact animals. We found a similar number of BrdU-labeled cells in sham-operated than in CB-grafted animals, suggesting that CB graft has no effect on progenitor cell migration. CB-grafted animals exhibited a significantly larger percentage of newborn cells (BrdU/Neuronal Nuclei-labeled cells) respect to 6-OHDA-lesioned and sham-operated animals. This study suggests that striatal CB graft might promote differentiation of SVZ progenitor cells into neurons, probably by the growth factors contained in CB cells.
在脑室下区（SVZ）产生的祖细胞向嗅球（OB）迁移，在那里它们分化为神经元。生长因子已被证明可促进SVZ/OB系统中的神经发生，而多巴胺能损伤则产生相反的效果。由于颈动脉体（CB）细胞在此处表达生长因子，我们研究了纹状体内CB移植对偏侧帕金森病大鼠SVZ/OB系统中神经祖细胞迁移和分化的影响。给完整的、6-羟基多巴胺（6-OHDA）损伤的以及移植了赋形剂或大鼠CB细胞的6-OHDA损伤动物注射溴脱氧尿苷（BrdU）。通过量化SVZ/OB系统中BrdU标记的细胞来评估祖细胞的迁移，并通过OB中新生神经元的比例来评估神经元分化。通过CB细胞形态及其酪氨酸羟化酶表达来确认移植的存活情况。其中一些CB细胞被BrdU染色，从而表明它们具有自我更新的能力。移植的球细胞还表达脑源性神经营养因子（BDNF）、胶质细胞源性神经营养因子（GDNF）、表皮生长因子（EGF）和血管内皮生长因子（VEGF）。与完整动物相比，6-OHDA损伤动物中神经祖细胞的迁移显著减少。我们发现假手术动物和CB移植动物中BrdU标记细胞的数量相似，这表明CB移植对祖细胞迁移没有影响。与6-OHDA损伤动物和假手术动物相比，CB移植动物中新生细胞（BrdU/神经元细胞核标记细胞）的百分比显著更高。这项研究表明，纹状体CB移植可能通过CB细胞中所含的生长因子促进SVZ祖细胞向神经元的分化。
