Distribution and immunohistochemical localization of GDNF protein in selected neural and non-neural tissues of rats during development and changes in unilateral 6-hydroxydopamine lesions

The tissue distribution of glial cell line-derived neurotrophic factor (GDNF) during development and changes in GDNF levels by unilateral 6-hydroxydopamine lesions were investigated in rats using a newly established enzyme immunoassay system and by immunohistochemistry. The detection limit of the assay was 0.3 pg/0.2 ml and the system recognized glycosylated mature GDNF. Concentrations of GDNF were relatively high in the kidney and testis during the embryonic and neonatal periods, respectively, and decreased with age. In the striatum, hippocampus and brain stem, GDNF reached a maximal level at around postnatal day 14. However, brain levels were generally lower than those in non-neural tissues. In the CNS, GDNF immunoreactivity was observed in striatal neurons, pyramidal neurons in the hippocampus and the Vth layer of the cortex, large neurons in the diagonal band and brain stem, and spinal motor neurons. It was also evident in several non-neural, tissue-specific cells, such as cells in the renal collecting ducts and distal tubules, and testicular Sertoli cells. Destruction of nigral dopaminergic neurons by 6-hydroxydopamine enhanced the levels of striatal GDNF protein, with apparent involvement of astrocytes. These results suggest that GDNF is normally synthesized in neurons, but may also be produced by astroglial cells in damaged brains.