Artikel
The neuronal progenitor cell migration/differentiation balance is influenced by brain-derived neurotrophic factor levels
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Veröffentlicht: | 28. April 2011 |
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Gliederung
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Objective: Throughout life, newborn progenitor cells in the subventricular zone (SVZ) migrate rostrally and differentiate into interneurons of the olfactory bulb (OB). Brain-derived neurotrophic factor (BDNF) may influence the physiological process of this migration.
Methods: In the present study, SVZ explant cultures from newborn mice (P=7 days) were used to characterize how this molecule may modulate the behavior of these migrating progenitors. The SVZ explants were embeded into a collagen gel and immunostainings for neuronal markers were performed. PCR analysis for the quantitative detection of BDNF in the SVZ and the olfactory bulb had been performed.
Results: Migration was stimulated by concentrations of BDNF in the physiological range, e.g., 1 ng/ml, whereas doses of 10 ng/ml or higher induced SVZ cell differentiation and reduced migration. The differentiation of SVZ-progenitors by high-dose BDNF application is initiated through MAP-kinase. Pharmacological inhibition of MAP-kinase blocked the BDNF-induced differentiation of SVZ-progenitors.
Conclusions: Physiological concentrations of BDNF, similar to polysialic acid (PSA) in tissue, stimulated emigration of cells from the explant without affecting their migration speed. Interestingly, in vivo immunohistochemical and molecular analysis showed similar levels of BDNF in both the SVZ and OB, indicating that there is no positive gradient to attract SVZ cells towards the OB. Therefore, SVZ cells respond differently to distinct BDNF concentrations.
CAVE: The Data are accepted for publication in the Journal of Clinical Neuroscience