Immunohistochemical localization of glial cell line-derived neurotrophic factor in the human central nervous system

Glial cell line-derived neurotrophic factor, initially purified from the ra t glial cell line B49, has the ability to promote the survival and differen tiation of various types of neurons in the central and peripheral nervous s ystems. In the present study, to evaluate the physiological role of glial c ell line-derived neurotrophic factor in the central nervous system, we inve stigated the cellular and regional distribution of glial cell line-derived neurotrophic factor immunoreactivity in autopsied control human brains and spinal cords using a polyclonal glial cell line-derived neurotrophic: facto r-specific antibody. On western blot analysis, the antibody reacted with re combinant human glial cell line-derived neurotrophic factor, and recognized a single band at a molecular weight of approximately 34,000 in human brain homogenates. Glial cell line-derived neurotrophic factor immunoreactivity was observed mainly in the neuronal somata, dendrites and axone. In the tel encephalon, diencephalon and brainstem, the cell bodies and proximal proces ses of several neuronal subtypes were immunostained with punctate dots. Fur thermore, immunopositive nerve fibers were also observed, and numerous axon s were intensely immunolabeled in the internal segment of the globus pallid us and the pars reticulata of the substantia nigra. In the cerebellum, the most conspicuous immunostaining was found in the Purkinje cells, in which t he somata and dendrites were strongly immunolabeled. Intense immunoreactivi ty was also detected in the posterior horn of the spinal cord, in addition to the neuronal elements, immunopositive glial cell bodies and processes we re observed in various regions. Our results suggest that glial cell line-derived neurotrophic factor is wid ely localized, but can be found selectively in certain neuronal subpopulati ons of the human central nervous system. Glial cell line-derived neurotroph ic factor may regulate the maintenance of neuronal functions under normal c ircumstances. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.