The glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic substance in the central and peripheral nervous systems. The present immunohistochemical study clarified the ultrastructural localization of GDNF-immunoreactive substance (GDNF-IR) accumulated at transfected sciatic nerve stumps and also at normal spinal dorsal horn, and has demonstrated that GDNF-IR products appear to be located in dense-cored vesicles within the axons. Furthermore, to determine the source of proximally accumulated GDNF in the transected sciatic nerve, we attempted a transection and a double ligation maneuver involving the sciatic nerve. In the early period after the ligation (20 h), GDNF-IR fibers were observed in the proximal and distal segment 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 Schwann cells in the proximal and distal stumps of transected nerve. These findings suggest that most of GDNF-IR was transported from the proximal or distal side in the early period, but was locally synthesized by Schwann cells around the ligations in the late period. Spinal rhizotomy caused prominent accumulation of GDNF-IR products at the cut end of the ganglion side of the dorsal root, but not at the ventral root. These results suggested that dorsal 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 after the colchicine treatment may support the above suggestion. In conclusion, the present results strongly suggest that a subgroup of DRG sensory neurons synthesized GDNF-containing dense-cored vesicles in the neuronal somata and anterogradely transports the vesicles to peripheral or central axon terminals.

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