Rescue of dorsal root sensory neurons by nerve growth factor and neurotrophin-3, but not brain-derived neurotrophic factor or neurotrophin-4, is dependent on the level of the p75 neurotrophin receptor

Neuroscience. 1998 Aug;85(4):1321-8. doi: 10.1016/s0306-4522(98)00006-2.

Abstract

Sensory neurons isolated from dorsal root ganglia of postnatal mice were analysed for cell surface p75, using fluorescent antibody staining with flow cytometry. They were found to follow a single bell-shaped distribution of p75 level, with no discrete group of p75-negative neurons. Sensory neurons were then separated by fluorescence-activated cell sorting into high- and low-p75 populations, consisting of cells within the highest and lowest 15th percentiles, respectively, of p75 expression levels. The sorted neurons were tested for trkA staining. All high-p75 neurons were positive for trkA, while many low-p75 cells were negative for trkA. The sorted neurons were placed in culture, and their survival in the absence and presence of various neurotrophins was measured. Low-p75 cells were found to have enhanced survival in the absence of neurotrophins, while cells with high p75 levels had reduced survival, compared to the overall population. Almost all high-p75 neurons were rescued with nerve growth factor, whereas less than half of the low-p75 cells were rescued. The slope of the dose response to nerve growth factor did not differ markedly between high- and low-p75 cells. High-p75, but not low-p75, neurons were responsive to neurotrophin-3. There was only a small response to either brain-derived neurotrophic factor or neurotrophin-4 in both high- and low-p75 neurons. All low-p75 neurons, and 68% of high-p75 neurons, survived in the presence of ciliary neurotrophic factor. These results, while consistent with our hypothesis that p75 may act as a death factor in postnatal sensory neurons, also imply a role for p75 in the modulation of trk responsiveness to neurotrophins. They also indicate overlapping neurotrophin responses in sensory neurons, especially in those with high p75 levels. A large proportion of low-p75 cells were not responsive to any of the nerve growth factor-related neurotrophins, suggesting an important role for cytokines such as ciliary neurotrophic factor and leukaemia inhibitor factor in the survival of sensory neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Cell Survival / drug effects
  • Fluorescent Antibody Technique
  • Ganglia, Spinal / cytology*
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Image Cytometry
  • Mice
  • Mice, Inbred C57BL
  • Nerve Growth Factors / pharmacology*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurotrophin 3
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Nerve Growth Factor
  • Receptor, trkA
  • Receptors, Nerve Growth Factor / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Neurotrophin 3
  • Proto-Oncogene Proteins
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • neurotrophin 4