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Authors & Affiliations
Silvia Silva Hucha, M. Estrella Fernández de Sevilla, Kirsty M Humphreys, Fiona E Benson, Ángel M Pastor, Sara Morcuende
Abstract
ALS is a progressive neurodegenerative disease characterised by the loss of motoneurons (MNs). Some MNs present a lower vulnerability to the disease, including neurons of the oculomotor system (OCM), compared to other cranial MNs (facial or hypoglossal). Vascular endothelial growth factor (VEGF) has shown the ability to protect MNs from degeneration. Overexpression of VEGF is involved in neuroprotection and delayed neurodegeneration of MNs. We have previously described a higher amount of VEGF in the extraocular neurons in control adult rats. The objective of this study in the murine SOD1G93A ALS model was to determine the survival rate of brainstem MNs and the expression of VEGF in the OCM nuclei compared to other vulnerable brainstem motor nuclei throughout the progression of the neurodegenerative disease. So, we study VEGF expression in OCM, facial and hypoglossal MNs at different survival stages (8, 12 or 16 weeks) in control and SOD1 animals. We used stereological methods, western blotting and immunohistochemistry techniques. Our results indicated a loss of MNs only in facial and hypoglossal nuclei. Furthermore, a significantly higher level of VEGF was detected in the more resistant MNs, the extraocular ones. We also analysed the localisation of the nuclear protein TDP-43, described as a hallmark for ALS in humans. However, no TDP-43 protein was detected in the cytoplasm of any brainstem MNs of our model. In conclusion, our data suggest that the increased level of VEGF observed in extraocular MNs could be a possible key to explaining the resistance of oculomotor nuclei in ALS.