Paracrine Interactions of BDNF Involving NGF-dependent Embryonic Sensory Neurons

The expression of BDNF mRNA by a proportion of embryonic dorsal root ganglion neurons has led to the proposal that BDNF acts by an autocrine loop on these neurons. To clarify the role of BDNF expression in developing sensory neurons, we measured the level of BDNF mRNA in purified populations of cranial sensory neurons that depend on either NGF or BDNF for survival. When neuronal death is taking place, the highest levels of BDNF mRNA were detected in NGF-dependent cutaneous sensory neurons. BDNF mRNA was expressed at lower levels in BDNF-dependent cutaneous sensory neurons and was undetectable in BDNF-dependent proprioceptive neurons. In coculture, NGF-dependent neurons promoted the survival of BDNF-dependent neurons by the production and release of BDNF. Depolarizing levels of KCl increased the expression of BDNF mRNA in cultured sensory neurons and this effect was partially inhibited by calcium channel antagonists. Our results suggest that during the phase of naturally occurring neuronal death, BDNF acts by a paracrine mechanism in sensory neurons and that BDNF expression is regulated by neural activity.