Dynamic patterns of BDNF expression in injured sensory neurons: differential modulation by NGF and NT-3

It has been suggested that altered retrograde neurotrophin support contributes to the phenotypic switch observed in BDNF expression in injured sensory neurons. Thus, modulatory influences of NGF and NT‐3 on BDNF expression in injured adult rat DRG neurons were examined using in situ hybridization and immunohistochemical approaches. Quantitative analysis reveals a biphasic response to sciatic nerve injury, whereby in the first day following injury, BDNF expression is up‐regulated in ≈83% of injured neurons including all small neurons, and a larger pool of trkB expressing neurons than in intact. By 1 week and up to 3 weeks later expression is still seen in ≈66% of injured neurons, but the characteristic phenotypic switch in the subpopulations expressing BDNF occurs, whereby expression in the trkA population is reduced and expression in trkB‐ and in trkC‐positive neurons is elevated. NGF infusion results in elevated levels of BDNF expression in both intact and injured trkA‐positive neurons, accompanied by reduced trkB expression. NT‐3 acts in an opposite fashion effecting a down‐regulation in BDNF expression in intact neurons and preventing/reducing the injury‐associated increases in BDNF expression in both trkC‐ and nontrkC‐expressing subpopulations of injured neurons. These effects suggest NGF can regulate BDNF expression in trkA‐expressing neurons regardless of the axonal state and that elevated levels of BDNF may contribute to the down‐regulation in trkB expression associated with these states. Furthermore, the findings demonstrate that NT‐3 can act in an antagonistic fashion to NGF in the regulation of BDNF expression in intact neurons, and mitigate BDNF's expression in injured neurons.