Abstract
Recent studies show a relationship between the deficit of vascular endothelial growth factor (VEGF) and motoneuronal degeneration, such as that occurring in amyotrophic lateral sclerosis (ALS). VEGF delivery protects motoneurons from cell death and delayed neurodegeneration in animal models of ALS. Strikingly, extraocular motoneurons show lesser vulnerability to neurodegeneration in ALS compared to other cranial or spinal motoneurons. Therefore, the present study investigates possible differences in VEGF and its main receptor VEGFR-2 or Flk-1 between extraocular and non-extraocular brainstem motoneurons. We performed immunohistochemistry and Western blot to determine the presence of VEGF and Flk-1 in rat motoneurons located in the three extraocular motor nuclei (abducens, trochlear and oculomotor) and to compare it to that observed in two other brainstem nuclei (hypoglossal and facial) that are vulnerable to degeneration. Extraocular motoneurons presented higher amounts of VEGF and its receptor Flk-1 than other brainstem motoneurons, and thus these molecules could be participating in their higher resistance to neurodegeneration. In conclusion, we hypothesize that differences in VEGF availability and signaling could be a contributing factor to the different susceptibility of extraocular motoneurons, when compared with other motoneurons, in neurodegenerative diseases.
Highlights
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a progressive loss of upper and lower motoneurons in the central nervous system
The major aim of the present work has been to determine whether the lower vulnerability to degeneration observed in extraocular motoneurons [2,3,5,29,32], when compared to other cranial motoneurons, could be explained by a higher trophic support by vascular endothelial growth factor (VEGF), according to recent evidences linking the deficit in this factor with motoneuron disease [20]
We explored and quantitatively compared the presence of VEGF and the expression of its Higher level of VEGF and Flk-1 in extraocular motoneurons receptor Flk-1 between different populations of cranial motoneurons, by means of immunohistochemistry at the confocal microscopy level and Western blot analysis
Summary
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a progressive loss of upper and lower motoneurons in the central nervous system. Not all motoneurons are vulnerable to the disease. Whilst most motoneuron pools are damaged, motoneurons of the oculomotor system are resistant to neurodegeneration in ALS. At early stages of the disease, a severe neuronal loss is consistently observed in the facial, trigeminal and hypoglossal nuclei, producing profound deficits of tongue motility, dysphagia and dysarthria [1,2].
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