Vascular endothelial growth factor (VEGF) stimulates neurogenesis
            <i>in vitro</i>
            and
            <i>in vivo</i>

Jin, Kunlin; Zhu, Y.; Sun, Yunjuan; Mao, Xiao Ou; Xie, Lin; Greenberg, David A.

doi:10.1073/pnas.182296499

Cited by 1,361 publications

(1,032 citation statements)

References 44 publications

Supporting

Mentioning

967

Contrasting

Unclassified

Order By: Relevance

“…DCX has become a widely used marker for newly generated neuroblasts in proliferative zones in adult 14,31,53,54 . In these regions, DCX is expressed exclusive of GFAP positive cells, and appears to be one of the earliest markers for cells transitioning from astrocytic glia to neuroblasts in the SVZ and RMS 32 .…”

Section: Role Of DCX In the Rmsmentioning

confidence: 99%

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

et al. 2006

View full text Add to dashboard Cite

The ability of the mature mammalian nervous system to continually produce neuronal precursors is of considerable importance, as manipulation of this process might one day permit the replacement of cells lost as a result of injury or disease. In mammals, the anterior subventricular zone (SVZa) region is one of the primary sites of adult neurogenesis. Here we show that Doublecortin (DCX), a widely used marker for newly generated neurons, when deleted in mouse results in a severe morphological defect in the rostral migratory stream and delayed neuronal migration that is independent of direction or responsiveness to Slit chemorepulsion. DCX is required for nuclear translocation and maintenance of bipolar morphology during migration of these cells. Our data identifies a critical function for DCX in the movement of newly generated neurons in the adult brain.In the rodent and primate brain, the anterior region of the lateral ventricle and the hippocampus are the primary sites of adult neurogenesis [1][2][3][4][5][6][7] . These neuroblasts, upon completing migration, are capable of maturing into fully differentiated neurons, integrating into local synaptic circuits and may be important in adult cognitive processing [8][9][10][11] .The mechanisms controlling the targeted translocation of large numbers of cells to the olfactory bulb (OB) over a considerable distance (>5 mm in the adult mouse) are an issue of intense investigation. These neurons translocate using a process known as chain migration, whereby the cells use each other as the migratory substrate 12 . These newly generated neurons are derived from SVZa glial fibrillary acidic protein (GFAP)-positive astrocytes 13,14 , which also ensheath them as they move through extensive interconnected networks along the lining of the lateral ventricle in the rostral forebrain and the rostral migratory stream (RMS) 15 . There, they are under the control of extracellular migration guidance cues, including the secreted ligands Slit and Reelin [16][17][18][19] , the receptors ErbB4 and Deleted in Colorectal Carcinoma (DCC) 20,21 , as well as integrins and neural cell adhesion molecule [21][22][23] . Upon reaching the bulb, the neurons turn and migrate in a radial direction 24 , integrating into either the granule cell layer or the periglomerular network 25 . 3The X-linked gene doublecortin (DCX) is mutated in some patients with the severe neuronal migration defect called classical lissencephaly or double cortex syndrome 26,27 . This migration defect is likely to be cell autonomous, because in females with a heterozygous mutation, approximately half of the neurons are misplaced within the cerebral cortex as would be expected from random X-chromosome inactivation. As a result, males display a four-layered agyric cortex and females display a subcortical band of heterotopic neurons. It was surprising, therefore, that the Dcx knockout mice displayed no appreciable defect in cortical neuronal lamination or positioning 28 . One possible explanation for these species differences ...

show abstract

Section: Role Of DCX In the Rmsmentioning

confidence: 99%

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Vascular endothelial growth factor is an angiogenic agent, which promotes neurogenesis and stem-progenitor cell migration (Jin et al, 2002;Sun et al, 2003). Likewise, BDNF regulates neuronal survival, cell migration, and synaptic function (Aguado et al, 2003;Gorski et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin Induction of VEGF and BDNF Promotes Brain Plasticity after Stroke in Mice

Chen¹,

Zhang²,

Jiang³

et al. 2005

J Cereb Blood Flow Metab

400

335

View full text Add to dashboard Cite

Molecular mechanisms underlying the role of statins in the induction of brain plasticity and subsequent improvement of neurologic outcome after treatment of stroke have not been adequately investigated. Here, we use both in vivo and in vitro studies to investigate the potential roles of two prominent factors, vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF), in mediating brain plasticity after treatment of stroke with atorvastatin. Treatment of stroke in adult mice with atorvastatin daily for 14 days, starting at 24 hours after MCAO, shows significant improvement in functional recovery compared with control animals. Atorvastatin increases VEGF, VEGFR2 and BDNF expression in the ischemic border. Numbers of migrating neurons, developmental neurons and synaptophysin-positive cells as well as indices of angiogenesis were significantly increased in the atorvastatin treatment group, compared with controls. In addition, atorvastatin significantly increased brain subventricular zone (SVZ) explant cell migration in vitro. Anti-BDNF antibody significantly inhibited atorvastatin-induced SVZ explant cell migration, indicating a prominent role for BDNF in progenitor cell migration. Mouse brain endothelial cell culture expression of BDNF and VEGFR2 was significantly increased in atorvastatin-treated cells compared with control cells. Inhibition of VEGFR2 significantly decreased expression of BDNF in brain endothelial cells. These data indicate that atorvastatin promotes angiogenesis, brain plasticity and enhances functional recovery after stroke. In addition, VEGF, VEGFR2 and BDNF likely contribute to these restorative processes.

show abstract

“…Basal laminae arising from blood capillaries are thought to concentrate growth factors secreted from the neural stem cell microenvironment via binding to heparan sulfate glycosaminoglycans (Mercier et al, 2002). 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).…”

Section: Introductionmentioning

confidence: 99%

“…VEGF plays a central regulatory role in the process of angiogenesis and is the most important factor in vascular development and neovascularization (Xie et al, 2004). Recent evidence indicates that VEGF can act as a neurotrophic factor and that VEGF produces neurogenic effects on neuronal progenitors (Jin et al, 2002). Zhang et al showed that VEGF is a powerful activator for immature neural progenitor cells and that VEGF could guide blood vessel growth and neural stem cell migration in the developing mammalian brain (Zhang et al, 2003).…”

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

View full text Add to dashboard Cite

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,

show abstract

Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo

Cited by 1,361 publications

References 44 publications

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

Atorvastatin Induction of VEGF and BDNF Promotes Brain Plasticity after Stroke in Mice

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

Contact Info

Product

Resources

About