Ultrastructural study of anterograde transport of glial cell line-derived neurotrophic factor from dorsal root ganglion neurons of rats towards the nerve terminal

The glial cell line-derived neurotrophic factor (GDNF) is a potent neurotro phic substance in the central and peripheral nervous systems. The present i mmunohistochemical study clarified the ultrastructural localization of GDNF -immunoreactive substance (GDNF-IR) accumulated at transfected sciatic nerv e stumps and also at normal spinal dorsal horn, and has demonstrated that G DNF-IR products appear to be located in dense-cored vesicles within the axo ns. Furthermore, to determine the source of proximally accumulated GDNF in the transected sciatic nerve, we attempted a transection and a double ligat ion maneuver involving the sciatic nerve. In the early period after the lig ation (20 h), GDNF-IR fibers were observed in the proximal and distal segme nt of the ligations, but no immunoreactivities were detected in the middle segment. On the other hand, at a late period (8 days) after the transection , GDNF-IR fibers had almost disappeared, but weak GDNF-IR was observed in S chwann cells in the proximal and distal stumps of transected nerve. These f indings suggest that most of GDNF-IR was transported from the proximal or d istal side in the early period, but was locally synthesized by Schwann cell s around the ligations in the late period. Spinal rhizotomy caused prominen t accumulation of GDNF-IR products at the cut end of the ganglion side of t he dorsal root, but not at the ventral root. These results suggested that d orsal root ganglionic (DRG) sensory neurons are one of the origins of GDNF. The fact that small- to medium-sized DRG neurons show enhanced GDNR-IR aft er the colchicine treatment may support the above suggestion. In conclusion , the present results strongly suggest that a subgroup of DRG sensory neuro ns synthesized GDNF-containing dense-cored vesicles in the neuronal somata and anterogradely transports the vesicles to peripheral or central axon ter minals. Copyright (C) 2001 S. Karger AG, Basel.