Extraocular motoneurons of the adult rat show higher levels of vascular endothelial growth factor and its receptor Flk-1 than other cranial motoneurons

PLoS One. 2017 Jun 1;12(6):e0178616. doi: 10.1371/journal.pone.0178616. eCollection 2017.

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.

MeSH terms

  • Animals
  • Blotting, Western
  • Brain Stem / cytology
  • Brain Stem / metabolism*
  • Motor Neurons / metabolism*
  • Rats
  • Rats, Wistar
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2

Grants and funding

This work was supported by grants from Ministerio de Industria y Competitividad (MINECO-FEDER) BFU2015-64515-P and BFU2012-33975 and Junta de Andalucía (CVI-6053) to AMP [http://www.mineco.gob.es/portal/site/mineco/, http://www.juntadeandalucia.es/temas/estudiar/investigacion/financiacion.html]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.