Neuroprotective Effect of Vascular Endothelial Growth Factor on Motoneurons of the Oculomotor System

Abstract

Vascular endothelial growth factor (VEGF) was initially characterized as a potent angiogenic factor based on its activity on the vascular system. However, it is now well established that VEGF also plays a crucial role as a neuroprotective factor in the nervous system. A deficit of VEGF has been related to motoneuronal degeneration, such as that occurring in amyotrophic lateral sclerosis (ALS). Strikingly, motoneurons of the oculomotor system show lesser vulnerability to neurodegeneration in ALS compared to other motoneurons. These motoneurons presented higher amounts of VEGF and its receptor Flk-1 than other brainstem pools. That higher VEGF level could be due to an enhanced retrograde input from their target muscles, but it can also be produced by the motoneurons themselves and act in an autocrine way. By contrast, VEGF’s paracrine supply from the vicinity cells, such as glial cells, seems to represent a minor source of VEGF for brainstem motoneurons. In addition, ocular motoneurons experiment an increase in VEGF and Flk-1 level in response to axotomy, not observed in facial or hypoglossal motoneurons. Therefore, in this review, we summarize the differences in VEGF availability that could contribute to the higher resistance of extraocular motoneurons to injury and neurodegenerative diseases.

Changes in adenosine and neurotrophic signaling in the SOD1G93A mouse model of amyotrophic lateral sclerosis: modulation by chronic caffeine intake

“…We thus hypothesized that the negative influence of caffeine upon ALS progression could result from a change in adenosine receptor density levels that in turn would affect neurotrophic factor signaling. Since VEGF is downregulated in cells overexpressing SOD1 G93A protein 12 , VEGF mRNA is downregulated in the spinal cord of SOD1 G93A mice 12 , and VEGF signaling has neuroprotective roles in motor neurons 62,10 , we first addressed the possibility that caffeine could affect VEGF signaling. However, while comparing the levels of VEGF or VEGF receptors in late stage of the SOD1 G93A mice treated/ non-treated with caffeine, no significant alterations that could be attributed to caffeine were detected.…”

“…In spite of the above-mentioned controversy, most of the evidence points towards a neuroprotective function of VEGF in ALS 6, 24,10 . Indeed, VEGF is a potent angiogenic and vascular permeability-enhancing factor, and both actions are very effective in hypoxia, therefore relevant in late stages of ALS.…”

Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis

“…Massive entry of calcium into the cell stimulates phospholipases, proteases and endonucleases, causing devastation of energy metabolism and apoptotic or necrotic cell death. Besides, reduced expression of astrocytic excitatory amino-acid transporters (EAATs) is crucial for clearance of glutamate from the synaptic cleft into astrocytes, and defects in glutamate transport have been linked with ALS pathogenesis [ 102 , 103 , 104 ].…”

Uwhangchungsimwon Inhibits Oxygen Glucose Deprivation/Re-Oxygenation-Induced Cell Death through Neuronal VEGF and IGF-1 Receptor Signaling and Synaptic Remodeling in Cortical Neurons

“…Angiogenesis is closely linked to neurogenesis during axon growth and neuronal recovery. Most studies have reported that VEGF expression has a potent effect on neurons as a direct angiogenic or neurotrophic factor that promotes neuronal survival, growth, and axonal outgrowth [ 9 ]. Therefore, enhancing the expression of angiogenic factors has been suggested as a therapeutic measure for reducing serious complications and resolving the symptoms after stroke.…”