Dataset Information

Dose-dependent effect of EGF on migration and differentiation of adult subventricular zone astrocytes.

ABSTRACT: Adult neural stem cells (NSCs) are located in the subventricular zone (SVZ), a specialized brain niche located on the walls of the lateral ventricle. Under physiological conditions, NSCs generate a large number of young neurons and some oligodendrocytes, however the mechanisms controlling cell proliferation and migration are unclear. In vitro, epidermal growth factor (EGF) signaling has been shown to be an important mediator of cell proliferation and migration in the adult brain; however, the primary SVZ progenitors that respond to EGF are not well known. In this study, we isolated SVZ type-B astrocytes and cultured them under different EGF concentrations. We found a dose-dependent effect of EGF on proliferation rates and migration of SVZ type-B astrocytes. We found that GFAP+ type-B astrocytes gave rise to highly migratory and proliferating cells that expressed Olig2 and NG2. After EGF withdrawal, a significant number of EGF-stimulated cells differentiated into S100beta+/O4+ oligodendrocytes. This study provides new insights about the production of oligodendrocytes derived from the astrocyte NSCs residing in the adult SVZ. To be able to manipulate the endogenous adult progenitors, it is crucial to identify and isolate the responding primary precursors and determine the extracellular signals that regulate their cell division, migration, and fate.

SUBMITTER: Gonzalez-Perez O

PROVIDER: S-EPMC2915565 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Dose-dependent effect of EGF on migration and differentiation of adult subventricular zone astrocytes.

Gonzalez-Perez Oscar O Quiñones-Hinojosa Alfredo A

Glia 20100601 8

Adult neural stem cells (NSCs) are located in the subventricular zone (SVZ), a specialized brain niche located on the walls of the lateral ventricle. Under physiological conditions, NSCs generate a large number of young neurons and some oligodendrocytes, however the mechanisms controlling cell proliferation and migration are unclear. In vitro, epidermal growth factor (EGF) signaling has been shown to be an important mediator of cell proliferation and migration in the adult brain; however, the pr ...[more]

PMID: 20187143

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Project description:The subventricular zone (SVZ) in lateral ventricles is the largest neurogenic region in adult brain containing high amounts of copper (Cu). This study aims to define the role of Cu in adult neurogenesis by chelating labile Cu ions using a well-established Cu chelator D-Penicillamine (D-Pen). A neurosphere model derived from adult mouse SVZ tissues was established and characterized for its functionality with regards to neural stem/progenitor cells (NSPCs). Applying D-Pen in cultured neurospheres significantly reduced intracellular Cu levels and reversed the Cu-induced suppression of NSPC's differentiation and migration. An in vivo intracerebroventricular (ICV) infusion model was subsequently established to infuse D-Pen directly into the lateral ventricle. Metal analyses revealed a selective reduction of Cu in SVZ by 13.1% (p = 0.19) and 21.4% (p < 0.05) following D-Pen infusions at low (0.075 μg/h) and high (0.75 μg/h) doses for 28 days, respectively, compared to saline-infused controls. Immunohistochemical studies revealed that the 7-day, low-dose D-Pen infusion significantly increased Ki67(+)/Nestin(+) cell counts in SVZ by 28% (p < 0.05). Quantification of BrdU(+)/doublecortin (DCX)(+) newborn neuroblasts in the rostral migration stream (RMS) and olfactory bulb (OB) further revealed that the short-term, low-dose D-Pen infusion, as compared with saline-infused controls, resulted in more newborn neuroblasts in OB, while the high-dose D-Pen infusion showed fewer newborn neuroblasts in OB but with more arrested in the RMS. Long-term (28-day) infusion revealed similar outcomes. The qPCR data from neurosphere experiments revealed altered expressions of mRNAs encoding key proteins known to regulate SVZ adult neurogenesis, including, but not limited to, Shh, Dlx2, and Slit1, in response to the changed Cu level in neurospheres. Further immunohistochemical data indicated that Cu chelation also altered the expression of high-affinity copper uptake protein 1 (CTR1) and metallothionein-3 (MT3) in the SVZ as well as CTR1 in the choroid plexus, a tissue regulating brain Cu homeostasis. Taken together, this study provides first-hand evidence that a high Cu level in SVZ appears likely to maintain the stability of adult neurogenesis in this neurogenic zone.

Dataset Information

Dose-dependent effect of EGF on migration and differentiation of adult subventricular zone astrocytes.

Publications

Dose-dependent effect of EGF on migration and differentiation of adult subventricular zone astrocytes.

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