VEGF - A Stimulus for Neuronal Development and Regeneration in the CNS and PNS

Theis, Verena; Theiß, Carsten

doi:10.2174/1389203719666180104113937

Cited by 42 publications

(30 citation statements)

References 85 publications

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“…The positive enrichment of genes located at the synaptic membrane and dendritic processes, points to effects on synaptic plasticity processes. Among the genes with the highest fold change response to L -lactate after 6 h, Vegfa is known to stimulate neuronal survival and axonal outgrowth ( Carmeliet and Storkebaum, 2002 ; Theis and Theiss, 2018 ), while Synj2 is implicated in recycling neurotransmitter vesicles ( Planchart, 2013 ), and Baiap2l2 ’s homolog Baiap2 has been implicated in dendritic spine development and NMDAR regulation ( Kang et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

L-Lactate Regulates the Expression of Synaptic Plasticity and Neuroprotection Genes in Cortical Neurons: A Transcriptome Analysis

Margineanu

Mahmood

Fiumelli

et al. 2018

Front. Mol. Neurosci.

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Lactate, a product of aerobic glycolysis in astrocytes, is required for memory formation and consolidation, and has recently emerged as a signaling molecule for neurons and various cell types in peripheral tissues. In particular lactate stimulates mRNA expression of a few plasticity-related genes. Here, we describe a RNA-seq study that unravels genome-wide transcriptomic responses to this energy metabolite in cortical neurons. Our results show that mRNA expression of 20 immediate-early genes involved in the MAPK signaling pathway and in synaptic plasticity were increased by more than twofold following 1 h of lactate stimulation. This effect was dependent on NMDA receptor (NMDAR) activity since it was prevented by pre-treatment with MK-801. Comparison with published datasets showed that a significant proportion of genes modulated by lactate were similarly regulated by a stimulation protocol activating specifically synaptic NMDARs known to result in upregulation of pro-survival and downregulation of pro-death genes. Remarkably, transcriptional responses to lactate were reproduced by NADH (for 74 of the 113 genes, FDR < 0.05), suggesting a redox-dependent mechanism of action. Longer-term gene expression changes observed after 6 h of lactate treatment affected genes involved in regulating neuronal excitability and genes coding for proteins localized at synapses. Gene set enrichment analyses performed with ranked lists of expressed genes revealed effects on molecular functions involved in epigenetic modulation, and on processes relevant to sleep physiology and behavioral phenotypes such as anxiety and hyperactivity. Overall, these results strengthen the notion that lactate effectively regulates activity-dependent and synaptic genes, and highlight new signaling effects of lactate in plasticity and neuroprotection.

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Section: Discussionmentioning

confidence: 99%

L-Lactate Regulates the Expression of Synaptic Plasticity and Neuroprotection Genes in Cortical Neurons: A Transcriptome Analysis

Margineanu

Mahmood

Fiumelli

et al. 2018

Front. Mol. Neurosci.

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“…VEGF signaling is critical for angiogenesis as well as vasculogenesis. VEGF-A stimulates VEGF receptors 1 and 2 (VEGFR-1 and VEGFR-2) on endothelial cells to initiate a diverseness of biological responses that serve to increase endothelial cell survival, migration, and differentiation [18,19,20,62,63]. The binding of VEGF to its receptor VEGFR-2 activates another pivotal mediator of angiogenesis: PLCγ1.…”

Section: C-cbl As a Major Regulator Of Angiogenesismentioning

confidence: 99%

c-Cbl: An Important Regulator and a Target in Angiogenesis and Tumorigenesis

Lyle

Belghasem

Chitalia

2019

Cells

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Casitas B lineage lymphoma (c-Cbl) is a multifunctional protein with a ubiquitin E3 ligase activity capable of degrading diverse sets of proteins. Although previous work had focused mainly on c-Cbl mutations in humans with hematological malignancies, recent emerging evidence suggests a critical role of c-Cbl in angiogenesis and human solid organ tumors. The combination of its unique structure, modular function, and ability to channelize cues from a rich network of signaling cascades, empowers c-Cbl to assume a central role in these disease models. This review consolidates the structural and functional insights based on recent studies that highlight c-Cbl as a target with tantalizing therapeutic potential in various models of angiogenesis and tumorigenesis.

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“…VEGF, initially described as a vascular permeability factor with specific mitogenic activity for endothelial cells [ 18 ], has a known direct neurotrophic and neuroprotective impact on glial and neuronal cells within the CNS and PNS [ 19 ]. In neurogenesis, VEGF is involved in axon growth, synaptogenesis, and synaptic plasticity [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment

Islamov

Bashirov

Fadeev

et al. 2020

IJMS

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The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.

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VEGF - A Stimulus for Neuronal Development and Regeneration in the CNS and PNS

Cited by 42 publications

References 85 publications

L-Lactate Regulates the Expression of Synaptic Plasticity and Neuroprotection Genes in Cortical Neurons: A Transcriptome Analysis

L-Lactate Regulates the Expression of Synaptic Plasticity and Neuroprotection Genes in Cortical Neurons: A Transcriptome Analysis

c-Cbl: An Important Regulator and a Target in Angiogenesis and Tumorigenesis

Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment

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