VEGF modulates synaptic activity in the developing spinal cord.
Although it has been documented that the nervous and the vascular systems share numerous analogies and are closely intermingled during development and pathological processes, interactions between the two systems are still poorly described. In this study, we investigated whether vascular endothelial growth factor (VEGF), which is a key regulator of vascular development, also modulates neuronal developmental processes. We report that VEGF enhances the gamma-aminobutyric acid (GABA)/glycinergic but not glutamatergic synaptic activity in embryonic spinal motoneurons (MNs), without affecting MNs excitability. In response to VEGF, the frequency of these synaptic events but not their amplitude was increased. Blocking endogenous VEGF led to an opposite effect by decreasing frequency of synaptic events. We found that this effect occurred specifically at early developmental stages (E13.5 and E15.5) and vanished at the prenatal stage E17.5. Furthermore, VEGF was able to increase vesicular inhibitory amino acid transporter density at the MN membrane. Inhibition of single VEGF receptors did not modify electrophysiological parameters indicating receptor combinations or an alternative pathway. Altogether, our findings identify VEGF as a modulator of the neuronal activity during synapse formation and highlight a new ontogenic role for this angiogenic factor in the nervous system.
Université Bordeaux, Angiogenesis and Tumor Microenvironment Laboratory, F-33615 Pessac Cedex France; INSERM, Angiogenesis and Tumor Microenvironment Laboratory, F-33615 Pessac Cedex, France.
Sylvaine
S
Guérit
Anne-Emilie
AE
Allain
Céline
C
Léon
William
W
Cazenave
Napoleone
N
Ferrara
Pascal
P
Branchereau
Andréas
A
Bikfalvi
D000200:Action Potentials / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001808:Blood Vessels / Q000378:metabolism; D004622:Embryo, Mammalian; D005998:Glycine / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology*; D055366:Synaptic Potentials / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018398:Homeodomain Proteins; D018377:Neurotransmitter Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C485184:enhanced green fluorescent protein; C467480:vascular endothelial growth factor A, mouse; C084059:Hb9 protein, mouse; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D005998:Glycine
angiogenic factors; development; neuronal activity; vascular endothelial growth factor