Modulation of vascular endothelial growth factor (VEGF) expression in motor neurons and its electrophysiological effects (original) (raw)

2008, Brain Research Bulletin

Previous studies have shown that VEGF expression in forebrain increases after experimental manipulations that increase neuronal activity [6,12]. One question is whether this also occurs in motor neurons. If so, it could be potentially advantageous from a therapeutic perspective, because VEGF prevents motor neuron degeneration [2,10,24]. Therefore, we asked whether endogenous VEGF expression in motor neurons could be modulated. We also asked what VEGF exposure would do to motor neurons using electrophysiology. Immunocytochemistry showed that motor neuron VEGF expression increased after a stimulus that increases neuronal and motor activity, i.e., convulsions. The increase in VEGF immunoreactivity occured in all motor neuron populations that were examined 24 hrs later. This effect was unlikely to be due to seizure-induced toxicity, because silver degeneration stain did not show the typical appearance of a dying or dead neuron. To address the effects of VEGF on motor neuron function, VEGF was applied directly to motor neurons while recording intracellularly, using a brainstem slice preparation. Exposure to exogenous VEGF (200 ng/ml) in normal conditions depressed stimulus-evoked depolarization of hypoglossal motor neurons. There was no detectable effect of VEGF on membrane properties or firing behavior. We suggest that the VEGF is upregulated in neurons when they are activated strongly, and VEGF depresses neuronal excitation as a compensatory mechanism. Failure of this mechanism may contribute to diseases that involve a dysregulation of VEGF, excessive excitation of motor neurons, and lead to motor neuron loss, such as amyotrophic lateral sclerosis (ALS).