Partial deletion of p75NTRin large-diameter DRG neurons exerts no influence upon the survival of peripheral sensory neuronsin vivo

The p75 neurotrophin receptor (p75(NTR)) is required for maintaining peripheral sensory neuron survival and function; however, the underlying cellular mechanism remains unclear. The general view is that expression of p75(NTR)by the neuron itself is required for maintaining sensory neuron survival and myelination in the peripheral nervous system (PNS). Adopting a neuronal-specific conditional knockout strategy, we demonstrate the partial depletion of p75(NTR)in neurons exerts little influence upon maintaining sensory neuron survival and peripheral nerve myelination in health and after demyelinating neuropathy. Our data show that the density and total number of dorsal root ganglion (DRG) neurons in 2-month-old mice is not affected following the deletion of p75(NTR)in large-diameter myelinating neurons, as assessed by stereology. Adopting experimental autoimmune neuritis induced in adult male mice, an animal model of demyelinating peripheral neuropathy, we identify that deleting p75(NTR)in myelinating neurons exerts no influence upon the disease progression, the total number of DRG neurons, and the extent of myelin damage in the sciatic nerve, indicating that the expression of neuronal p75(NTR)is not essential for maintaining peripheral neuron survival and myelination after a demyelinating insultin vivo. Together, results of this study suggest that the survival and myelination of peripheral sensory neurons is independent of p75(NTR)expressed by a subtype of neuronsin vivo. Thus, our findings provide new insights into the mechanism underpinning p75(NTR)-mediated neuronal survival in the PNS.