ENDOGENOUS BRAIN-DERIVED NEUROTROPHIC FACTOR IS ANTEROGRADELY TRANSPORTED IN PRIMARY SENSORY NEURONS

Neurotrophins are a family of proteins which act as survival and diffe rentiative factors in the developing and mature nervous system. Extens ive evidence has bern provided for their retrograde action following i ncorporation into nerve terminals and transport to the cell body. In c ontrast, we now demonstrate that one neurotrophin, brain-derived neuro trophic factor, is transported anterogradely via both peripheral and c entral processes of spinal sensory neurons. Using newly generated anti sera, we have examined the distribution of brain-derived neurotrophic factor immunoreactivity and found it to be present within a subpopulat ion of sensory somata, primarily those with a small-to-medium diameter . The immunoreactivity was accumulated on both the distal and proximal sides of a ligature on the sciatic nerve. The accumulation on the dis tal side, but not on the proximal side, was substantially reduced by p retreatment with brain-derived neurotrophic factor antibodies in vivo. In contrast to the periphery, the immunoreactivity only accumulated o n the proximal side of a lesion of the dorsal root. In the spinal cord , most nerve terminals immunoreactive for brain-derived neurotrophic f actor were identified in lamina II. Lesion of the dorsal root led to a reduction of these nerve terminals. These studies indicate that the f actor is transported not only retrogradely to, but also anterogradely from, the spinal ganglia to terminals in the periphery and spinal cord . The findings add a new dimension to the role of neuronal growth fact ors, since anterograde transport has not been observed previously for any endogenous survival factor. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.