title: VEGF protects motor neurons against excitotoxicity by upregulation of GluR2.
abstract: Influx of Ca(2+) ions through the α-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptors is toxic to neurons and contributes to motor neuron degeneration observed in amyotrophic lateral sclerosis (ALS). The Ca(2+) permeability of the AMPA receptor depends on its subunit composition. If the GluR2 subunit is present in the receptor complex, the AMPA receptor is impermeable to Ca(2+). In this study, we identified vascular endothelial growth factor-A (VEGF) as a GluR2 inducing molecule. Cultured motor neurons pretreated with VEGF displayed higher GluR2 levels. This resulted in AMPA receptor currents with a low relative Ca(2+) permeability and in motor neurons that were less vulnerable to AMPA receptor-mediated excitotoxicity. This effect of VEGF was mediated through the VEGFR2 present on the motor neurons and was due to stimulation of GluR2 transcription. Intracerebroventricular treatment with VEGF similarly induced GluR2 expression in the ventral spinal cord of rats and this mechanism contributes to the protective effect of VEGF on motor neurons.
authors.affiliation: Laboratory of Neurobiology, Experimental Neurology, K.U. Leuven, Leuven, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Bogaert
authors.forename: Philip
authors.initials: P
authors.lastname: Van Damme
authors.forename: Koen
authors.initials: K
authors.lastname: Poesen
authors.forename: Joke
authors.initials: J
authors.lastname: Dhondt
authors.forename: Nicole
authors.initials: N
authors.lastname: Hersmus
authors.forename: Dora
authors.initials: D
authors.lastname: Kiraly
authors.forename: Wendy
authors.initials: W
authors.lastname: Scheveneels
authors.forename: Wim
authors.initials: W
authors.lastname: Robberecht
authors.forename: Ludo
authors.initials: L
authors.lastname: Van Den Bosch
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D007276:Injections, Intraventricular / Q000379:methods; D009046:Motor Neurons / Q000378:metabolism* / Q000502:physiology; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000502:physiology*
chemical_list: D009498:Neurotoxins; D018091:Receptors, AMPA; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C104722:glutamate receptor ionotropic, AMPA 2