Upregulation of Flk-1 by bFGF via the ERK pathway is essential for VEGF-mediated promotion of neural stem cell proliferation

Xiao, Zhifeng; Kong, Yaxian; Yang, Shufa; Li, Meiyu; Wen, Jinhua; Li, Lingsong

doi:10.1038/sj.cr.7310126

Cited by 83 publications

(54 citation statements)

References 32 publications

(34 reference statements)

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“…The ability of curcumin to induce proliferation of neural stem cells was abolished by inhibitors of MEK/ERK and p38 MAP kinases, demonstrating a requirement for these kinases in the biological effect of curcumin on the stem cells. Previous studies have shown that MAP kinases mediate the proliferative effects of growth factors on neural stem cells (49). For example, basic fibroblast growth factor (FGF2) stimulates the proliferation of rat neural stem cells by an ERK-mediated mechanism (50), and FGF2 maintains mouse cortical NPC in a proliferative state by a mechanism involving ERK-mediated up-regulation of gap junctions (51).…”

Section: Discussionmentioning

confidence: 99%

Curcumin Stimulates Proliferation of Embryonic Neural Progenitor Cells and Neurogenesis in the Adult Hippocampus

Kim

Son

Park

et al. 2008

Journal of Biological Chemistry

312

225

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Curcumin is a natural phenolic component of yellow curry spice, which is used in some cultures for the treatment of diseases associated with oxidative stress and inflammation. Curcumin has been reported to be capable of preventing the death of neurons in animal models of neurodegenerative disorders, but its possible effects on developmental and adult neuroplasticity are unknown. In the present study, we investigated the effects of curcumin on mouse multi-potent neural progenitor cells (NPC) and adult hippocampal neurogenesis. Curcumin exerted biphasic effects on cultured NPC; low concentrations stimulated cell proliferation, whereas high concentrations were cytotoxic. Curcumin activated extracellular signal-regulated kinases (ERKs) and p38 kinases, cellular signal transduction pathways known to be involved in the regulation of neuronal plasticity and stress responses. Inhibitors of ERKs and p38 kinases effectively blocked the mitogenic effect of curcumin in NPC. Administration of curcumin to adult mice resulted in a significant increase in the number of newly generated cells in the dentate gyrus of hippocampus, indicating that curcumin enhances adult hippocampal neurogenesis. Our findings suggest that curcumin can stimulate developmental and adult hippocampal neurogenesis, and a biological activity that may enhance neural plasticity and repair.

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Section: Discussionmentioning

confidence: 99%

Curcumin Stimulates Proliferation of Embryonic Neural Progenitor Cells and Neurogenesis in the Adult Hippocampus

Kim

Son

Park

et al. 2008

Journal of Biological Chemistry

312

225

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“…Astrocytes of the neurogenic niches secrete vascular endothelial growth factor (VEGF) and the astrocyte-like precursor cells express Flk1, indicating both autocrine and paracrine VEGF signaling (Bernal and Peterson, in press). VEGF promotes the proliferation and survival of adult neural precursor cells (Cao et al, 2004;Schanzer et al, 2004;Xiao et al, 2007).…”

Section: Astrocyte-derived Growth Factors and Neurotrophic Factorsmentioning

confidence: 99%

Glial cells in adult neurogenesis

Morrens

Broeck

Kempermann

2011

Glia

163

101

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Adult neurogenesis is an exceptional feature of the adult brain and in an intriguing way bridges between neuronal and glial neurobiology. Essentially, all classes of glial cells are directly or indirectly linked to this process. Cells with astrocytic features, for example, serve as radial glia-like stem cells in the two neurogenic regions of the adult brain, the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles, producing new neurons, create a microenvironment permissive for neurogenesis, and are themselves generated alongside the new neurons in an associated but independently regulated process. Oligodendrocytes are generated from precursor cells intermingled with those generating neurons in an independent lineage. NG2 cells have certain precursor cell properties and are found throughout the brain parenchyma. They respond to extrinsic stimuli and injury but do not generate neurons even though they can express some preneuronal markers. Microglia have positive and negative regulatory effects as constituents of the "neurogenic niche". Ependymal cells play incompletely understood roles in adult neurogenesis, but under certain conditions might exert (back-up) precursor cell functions. Glial contributions to adult neurogenesis can be direct or indirect and are mediated by mechanisms ranging from gap-junctional to paracrine and endocrine. As the two neurogenic regions differ between each other and both from the non-neurogenic rest of the brain, the question arises in how far regionalization of both the glia-like precursor cells as well as of the glial cells determines site-specific "neurogenic permissiveness." In any case, however, "neurogenesis" appears to be an essentially glial achievement.

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“…Endothelial cells are known to synthesize numerous basal lamina elements and growth factors involved in neurogenesis, such as brain-derived neurotrophic factor and vascular endothelial growth factor (VEGF) (Mabie et al, 1999;Leventhal et al, 1999;Jin et al, 2002). Currently known factors that can stimulate neurogenesis, including basic fibroblast growth factor, VEGF, insulin like growth factor-1, and transforming growth factor-beta, can also promote endothelial cell survival, division, and differentiation (Xiao et al, 2007;Wang et al, 2007;Zhu et al, 2008;Sumioka et al, 2008). Coordinated interactions between endothelial cells and neural cell proliferation have been observed in the developing brain and during testosterone-induced neurogenesis in the adult song bird (Louissaint et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Endothelial cells promote neural stem cell proliferation and differentiation associated with VEGF activated Notch and Pten signaling

Sun

Zhou

et al. 2010

Developmental Dynamics

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To investigate whether and how endothelial cells affect neurogenesis, we established a system to co-culture endothelial cells and brain slices of neonatal rat and observed how subventricular zone cells differentiate in the presence of endothelial cells. In the presence of endothelial cells, neural stem cells increased in number, as did differentiated neurons and glia. The augmentation of neurogenesis was reversed by diminishing vascular endothelial growth factor (VEGF) expression in endothelial cells with RNA interference (RNAi). Microarray analysis indicated that expression levels of 112 genes were significantly altered by co-culture and that expression of 81 of the 112 genes recovered to normal levels following RNAi of VEGF in endothelial cells. Pathway mapping showed an enrichment of genes in the Notch and Pten pathways. These data indicate that endothelial cells promote neural stem cell proliferation and differentiation associated with VEGF, possibly by activating the Notch and Pten pathways. Developmental Dynamics 239:2345-2353,

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Upregulation of Flk-1 by bFGF via the ERK pathway is essential for VEGF-mediated promotion of neural stem cell proliferation

Cited by 83 publications

References 32 publications

Curcumin Stimulates Proliferation of Embryonic Neural Progenitor Cells and Neurogenesis in the Adult Hippocampus

Curcumin Stimulates Proliferation of Embryonic Neural Progenitor Cells and Neurogenesis in the Adult Hippocampus

Glial cells in adult neurogenesis

Endothelial cells promote neural stem cell proliferation and differentiation associated with VEGF activated Notch and Pten signaling

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