Striatal carotid body graft promotes differentiation of neural progenitor cells into neurons in the olfactory bulb of adult hemiparkisonian rats
Belzunegui S, Izal-Azcárate A, San Sebastián W, Garrido-Gil P, Vázquez-Claverie M, López B, Marcilla I, Luquin MR.
Laboratory of Regenerative Therapy, Department of Neurology, Neuroscience Division, Center for Applied Medical Research, University of Navarra, Avda. Pio XII 55, Pamplona, Spain.
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.
CITATION Brain Res. 2008 Jun 27;1217:213-20