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

Sensory neurons isolated from dorsal root ganglia of postnatal mice we re analysed for cell surface p75, using fluorescent antibody staining with flow cytometry. They were found to follow a single bell-shaped di stribution of p75 level, with no discrete group of p75-negative neuron s. 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 expressi on levels. The sorted neurons were tested for trkA staining. All high- p75 neurons were positive for trkA, while many low-p75 cells were nega tive for trkA. The sorted neurons were placed in culture, and their su rvival in the absence and presence of various neurotrophins was measur ed. Low-p75 cells were found to have enhanced survival in the absence of neurotrophins, while cells with high p75 levels had reduced surviva l, compared to the overall population. Almost all high-p75 neurons wer e 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-p 75, 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 neuron s, and 68% of high-p75 neurons, survived in the presence of ciliary ne urotrophic 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 neuro trophins. They also indicate overlapping neurotrophin responses in sen sory neurons, especially in those with high p75 levels. A large propor tion of low-p75 cells were not responsive to any of the nerve growth f actor-related neurotrophins, suggesting an important role for cytokine s such as ciliary neurotrophic factor and leukaemia inhibitory factor in the survival of sensory neurons. (C) 1998 IBRO. Published by Elsevi er Science Ltd.