Neurotrophin-4: a Survival Factor for Adult Sensory Neurons

The nerve growth factor (NGF) family of neurotrophins provides a substantial part of the normal trophic support for sensory neurons during development. Although these neurotrophins, which include Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin-4 (NT-4), continue to be expressed into adulthood, there is little evidence that they are survival factors for adult neurons. Here we have examined the age-dependent neurotrophic requirements of a specialized type of mechanoreceptive neuron, called a D-hair receptor, in the dorsal root ganglion (DRG). Studies using knockout mice have demonstrated that the survival of D-hair receptors is dependent upon both NT-3 and NT-4. Here, we show that the time period when D-hair receptors require these two neurotrophins is different. Survival of D-hair receptors depends on NT-3 early in postnatal development and NT-4 later in the mature animal. The age-dependent loss of D-hair neurons in older NT-4 knockout mice was accompanied by a large reduction (78%) in neurons positive for the NT-4 receptor (trkB) together with neuronal apoptosis in the DRG. This is the first evidence that sensory neurons have a physiological requirement for a single neurotrophin for their continued survival in the adult.