Vascular endothelial growth factor promotes neurite maturation in primary CNS neuronal cultures

Khaibullina, Alfia; Rosenstein, Jeffrey M.; Krum, Janette M.

doi:10.1016/j.devbrainres.2003.09.022

Cited by 109 publications

(78 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The notion of a direct response of neurons to VEGF is supported by reports on expression of the high-affinity VEGF receptors FLK1 and FLT1 and of the auxiliary nonsignaling receptor neuropilin on neuronal cells (6,(25)(26)(27). Also consistent with a direct mechanism are findings showing that VEGF can induce neurite growth in cultured cortical neurons (28)(29)(30). In vivo, however, a rigorous distinction between direct and indirect mechanisms may necessitate neuronal-, glial-, and endothelial-specific ablation (or functional knockdown) of each VEGF receptor.…”

Section: Discussionsupporting

confidence: 70%

Reversible modulations of neuronal plasticity by VEGF

Licht

Goshen

Avital

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

230

191

View full text Add to dashboard Cite

Neurons, astrocytes, and blood vessels are organized in functional “neurovascular units” in which the vasculature can impact neuronal activity and, in turn, dynamically adjust to its change. Here we explored different mechanisms by which VEGF, a pleiotropic factor known to possess multiple activities vis-à-vis blood vessels and neurons, may affect adult neurogenesis and cognition. Conditional transgenic systems were used to reversibly overexpress VEGF or block endogenous VEGF in the hippocampus of adult mice. Importantly, this was done in settings that allowed the uncoupling of VEGF-promoted angiogenesis, neurogenesis, and memory. VEGF overexpression was found to augment all three processes, whereas VEGF blockade impaired memory without reducing hippocampal perfusion or neurogenesis. Pertinent to the general debate regarding the relative contribution of adult neurogenesis to memory, we found that memory gain by VEGF overexpression and memory impairment by VEGF blockade were already evident at early time points at which newly added neurons could not yet have become functional. Surprisingly, VEGF induction markedly increased in vivo long-term potentiation (LTP) responses in the dentate gyrus, and VEGF blockade completely abrogated LTP. Switching off ectopic VEGF production resulted in a return to a normal memory and LTP, indicating that ongoing VEGF is required to maintain increased plasticity. In summary, the study not only uncovered a surprising role for VEGF in neuronal plasticity, but also suggests that improved memory by VEGF is primarily a result of increasing plasticity of mature neurons rather than the contribution of newly added hippocampal neurons.

show abstract

Section: Discussionsupporting

confidence: 70%

Reversible modulations of neuronal plasticity by VEGF

Licht

Goshen

Avital

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

230

191

View full text Add to dashboard Cite

show abstract

“…VEGF enhances neuronal proliferation (Jin et al, 2002;Zhu et al, 2003), neurite outgrowth and maturation (Rosenstein et al, 2003;Khaibullina et al, 2004), and neuronal survival (Jin et al, 2000(Jin et al, , 2001Svensson et al, 2002). A neuroprotective role for VEGF is supported by the demonstration that VEGF reduces excitotoxic damage to cultured hippocampal neurons (Jin et al, 2000;Matsuzaki et al, 2001;Svensson et al, 2002) and reduces damage in vivo after ischemia (Hayashi et al, 1998;Sun et al, 2003) (but see van Bruggen et al, 1999).…”

Section: Introductionmentioning

confidence: 85%

Depression of Synaptic Transmission by Vascular Endothelial Growth Factor in Adult Rat Hippocampus and Evidence for Increased Efficacy after Chronic Seizures

McCloskey¹,

Croll²,

Scharfman³

2005

J. Neurosci.

116

View full text Add to dashboard Cite

In addition to its potent effects on vasculature, it has become clear that vascular endothelial growth factor (VEGF) has effects on both neurons and glia, and recent studies suggest that it can be neuroprotective. To determine potential mechanisms underlying this neuroprotection, recombinant human VEGF was bath applied to adult rat hippocampal slices, and both extracellular and intracellular recordings were used to examine intrinsic properties and synaptic responses of hippocampal principal neurons. Initial studies in area CA1 showed that VEGF significantly reduced the amplitude of responses elicited by Schaffer collateral stimulation, without influencing membrane properties. Similar effects occurred in CA3 pyramidal cells and dentate gyrus granule cells when their major glutamatergic afferents were stimulated. Because VEGF expression is increased after seizures, effects of VEGF were also examined in rats with recurrent spontaneous seizures. VEGF reduced spontaneous discharges in slices from these rats but had surprisingly little effect on epileptiform discharges produced by disinhibition of slices from control rats. These results demonstrate a previously unknown effect of VEGF on neuronal activity and also demonstrate a remarkable potency in the epileptic brain. Based on this, we suggest that VEGF or VEGF-related targets could provide useful endpoints to direct novel therapeutic strategies for epilepsy.

show abstract

“…VEGF is expressed and released by endothelial cells [31,32] and its receptor Flk-1 is expressed by adult neural progenitors [22]. Recent studies demonstrate that VEGF signaling through Flk-1 increases proliferation of neuronal progenitors [33], stimulates adult neurogenesis in vitro and in vivo [34], and promotes neurite outgrowth [35,36]. The relationship between endothelial cells and neuronal precursors is dynamic and reciprocal, and in vitro models suggest a critical role for VEGF in the cross-talk between neuronal progenitors and endothelial cells [37].…”

Section: Vegf and Neurogenesismentioning

confidence: 99%