VEGF protects motor neurons against excitotoxicity by upregulation of GluR2
Autor: | Wendy Scheveneels, Koen Poesen, Philip Van Damme, Wim Robberecht, Dora Kiraly, Elke Bogaert, Joke Dhondt, Nicole Hersmus, Ludo Van Den Bosch |
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Rok vydání: | 2010 |
Předmět: |
Vascular Endothelial Growth Factor A
Aging Receptor complex Neurotoxins Excitotoxicity Stimulation AMPA receptor medicine.disease_cause Downregulation and upregulation medicine Animals Calcium Signaling Receptors AMPA Rats Wistar Receptor Cells Cultured Injections Intraventricular Motor Neurons Chemistry General Neuroscience Neurodegeneration Glutamate receptor medicine.disease Coculture Techniques Rats Up-Regulation Cell biology Spinal Cord nervous system Nerve Degeneration Neurology (clinical) Geriatrics and Gerontology Neuroscience Developmental Biology |
Zdroj: | Neurobiology of Aging. 31:2185-2191 |
ISSN: | 0197-4580 |
Popis: | 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. |
Databáze: | OpenAIRE |
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