AXOTOMY UP-REGULATES THE ANTEROGRADE TRANSPORT AND EXPRESSION OF BRAIN-DERIVED NEUROTROPHIC FACTOR BY SENSORY NEURONS

In addition to the known retrograde transport of neurotrophins, it is now evident that endogenous brain-derived neurotrophic factor (BDNF) i s transported in the anterograde direction in peripheral and central n eurons. We used a double-ligation procedure that distinguishes between anterograde and retrograde flow to quantify the anterograde transport of endogenous neurotrophins and neuropeptides in the peripheral nervo us system before and after axotomy. BDNF accumulation proximal to the ligation (anterograde transport) was twice that distal to the ligation (retrograde direction). Anterograde transport of nerve growth factor and neurotrophin-3 was not evident. Furthermore, BDNF anterograde tran sport increased 3.5-fold within 24 hr after sciatic nerve injury or do rsal rhizotomy. Anterograde transport of substance P and calcitonin ge ne-related peptide decreased after peripheral nerve lesion, demonstrat ing that there was no generalized increase in anterograde transport. T o determine the source of the anterogradely transported BDNF, we perfo rmed in situ hybridization in a variety of tissues before and after ax otomy. Expression of BDNF mRNA in proximal nerve segments did not chan ge with treatment, showing that the increased accumulation of BDNF was not a result of increased local synthesis. BDNF mRNA and protein were expressed by dorsal root ganglion sensory neurons but not by motor ne urons. BDNF mRNA expression was increased 1 d after nerve injury, and BDNF protein was also increased twofold to threefold, suggesting that sensory neurons are the major contributing source of the increased BDN F traffic in the sciatic nerve. Our results suggest that increased ant erogradely transported BDNF plays a role in the early neuronal respons e to peripheral nerve injury at sites distal to the cell body.