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 rat glial cell line B49, has the ability to promote the survival and differentiation of various types of neurons in the central and peripheral nervous systems. In the present study, to evaluate the physiological role of glial cell line-derived neurotrophic factor in the central nervous system, we investigated 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 factor-specific antibody. On western blot analysis, the antibody reacted with recombinant 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 axons. In the telencephalon, diencephalon and brainstem, the cell bodies and proximal processes of several neuronal subtypes were immunostained with punctate dots. Furthermore, immunopositive nerve fibers were also observed, and numerous axons were intensely immunolabeled in the internal segment of the globus pallidus and the pars reticulata of the substantia nigra. In the cerebellum, the most conspicuous immunostaining was found in the Purkinje cells, in which the somata and dendrites were strongly immunolabeled. Intense immunoreactivity was also detected in the posterior horn of the spinal cord. In addition to the neuronal elements, immunopositive glial cell bodies and processes were observed in various regions. Our results suggest that glial cell line-derived neurotrophic factor is widely localized, but can be found selectively in certain neuronal subpopulations of the human central nervous system. Glial cell line-derived neurotrophic factor may regulate the maintenance of neuronal functions under normal circumstances.