Vascular endothelial growth factor attenuates neurodegenerative changes in the NSC-34 motor neuron cell line induced by cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients

Neurodegener Dis. 2011;8(5):322-30. doi: 10.1159/000323718. Epub 2011 Mar 10.

Abstract

Background: Motor neuron disease or amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord as well as motor cortex. Recently, vascular endothelial growth factor (VEGF) has been identified as a neurotrophic factor in animal models of familial ALS and other neurological diseases.

Objective: The present study was designed to investigate the neuroprotective role of VEGF in the more prevalent sporadic form of ALS.

Methods: We studied the effect of VEGF on the NSC-34 cell line exposed to cerebrospinal fluid (CSF) from sporadic ALS patients (ALS-CSF) in terms of lactate dehydrogenase (LDH) assay as well as choline acetyltransferase (ChAT) and phosphorylated neurofilament expression by immunocytochemistry and confocal microscopy. NSC-34 cells were exposed to CSF from patients with definite ALS and compared to controls. LDH activity was assessed in the growth media, prior to and 24 h after the addition of VEGF to the cells. At similar time points, the cells were fixed and processed for immunocytochemistry to evaluate ChAT and phosphorylated neurofilament expression.

Results: Exposure to ALS-CSF caused morphological changes of NSC-34 cells like reduced differentiation and aggregation of phosphorylated neurofilaments. Enhanced LDH activity and reduced ChAT immunoreactivity were also observed. Addition of VEGF to NSC-34 cells exposed to ALS-CSF was protective in terms of reduced LDH activity and restoration of ChAT expression.

Conclusion: The present study confirms that VEGF exerts a neuroprotective effect on the NSC-34 cell line by attenuating the degenerative changes induced by ALS-CSF. It thus has therapeutic potential in sporadic ALS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid*
  • Amyotrophic Lateral Sclerosis / pathology
  • Cell Line
  • Cells, Cultured
  • Cerebrospinal Fluid / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Motor Neurons / pathology*
  • Nerve Degeneration / pathology*
  • Nerve Degeneration / prevention & control*
  • Pilot Projects
  • Vascular Endothelial Growth Factor A / physiology
  • Vascular Endothelial Growth Factor A / therapeutic use*

Substances

  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A