BDNF is involved in sympathetic sprouting in the dorsal root ganglia following peripheral nerve injury in rats.

Abstract

Peripheral nerve injury results in sympathetic sprouting around large diameter sensory neurons in the dorsal root ganglia (DRG). The mechanism underlying this pathological phenomenon is not known. Brain-derived neurotrophic factor (BDNF) is up-regulated in large sensory neurons and ensheathing satellite cells following a sciatic nerve injury. In the present study, we investigated the effects of BDNF on the sympathetic sprouting in the DRG, by delivering BDNF antibody or antisense oligodeoxynucleotide to injured DRGs, or by delivering exogenous BDNF to intact DRGs. The sheep antibody to BDNF, characterized by bioassays and dot blots, specifically reacted with BDNF but not other neurotrophins. Noradrenergic fibers were visualized by immunostaining of tyrosine hydroxylase (TH) and quantified by an NIH Imaging program. Two weeks following L5 spinal nerve lesion, a dramatic increase in TH-immunoreactive (-ir) fibres was observed in both ipsi- and contralateral DRGs in normal sheep IgG treated rats. BDNF antibody significantly reduced the sprouting of sympathetic nerves in both ipsi- and contra-lateral DRGs by 67% and 42% respectively. BDNF antisense oligodeoxynucleotide, by inhibiting BDNF synthesis in DRGs, also significantly suppressed the sprouting by 67% and 60% respectively in the ipsi- and contra-lateral DRGs. Delivery of exogenous BDNF into an intact L5 DRGs resulted in an increase in the sprouting by 4.2-fold. Our results clearly indicate that BDNF, synthesized in and secreted from the DRGs, is involved in the sympathetic sprouting in the DRG following the peripheral nerve injury.