Malonate-induced cortico-motoneuron death is attenuated by NT-4, but not by BDNF or NT-3

Neuroreport. 2001 May 25;12(7):1355-8. doi: 10.1097/00001756-200105250-00013.

Abstract

Neurotrophins are promising candidates to slow the progression of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease in which spinal and cortical motoneurons selectively degenerate. In a long-term in vitro model, malonate-induced toxicity and cell death of motoneurons have been demonstrated. Here we studied the neuroprotective effect of BDNF, NT-3, and NT-4 on the cell death of cortical motoneurons in an organotypic culture model after chronic mitochondrial inhibition with malonate. Our data show that NT-4 completely prevents malonate-induced toxicity, whereas BDNF or NT-3 had no neuroprotective effect. In clinical trials for ALS, predominantly focussed on the survival of spinal motoneurons, BDNF has already been tested with disappointing results; our results suggest that NT-4 may be a better neurotrophin to prevent motoneuron loss.

Publication types

  • Comparative Study

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Animals, Newborn
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Cells, Cultured / pathology
  • Disease Models, Animal
  • Immunohistochemistry
  • Malonates / pharmacology
  • Motor Cortex / cytology
  • Motor Cortex / drug effects*
  • Motor Cortex / metabolism
  • Motor Neurons / drug effects*
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / prevention & control
  • Nerve Growth Factors / pharmacology*
  • Neurofilament Proteins / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neurotrophin 3 / pharmacology
  • Organ Culture Techniques
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / pathology
  • Rats
  • Rats, Wistar
  • Receptor, trkB / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Malonates
  • Nerve Growth Factors
  • Neurofilament Proteins
  • Neuroprotective Agents
  • Neurotrophin 3
  • Receptor, trkB
  • neurotrophin 4