Expression of glial cell line-derived neurotrophic factor in the brain and cerebrospinal fluid of the developing rat

Abstract

Expression of GDNF in developing rat brain from PND 1 to 14 and on PND 21 was examined immunocytochemically. At PND 1, intense diffuse immunoreactivity was noted within the cytoplasm of a diverse group of neuronal and nonneuronal cells, including choroid plexus epithelial cells, ependymal cells, tanycytes of the third ventricle, and cellular elements in the subarachnoid compartment. GDNF expression became more localized among these cells from PND 7–14 and was almost undetectable by PND 21. Although GDNF-positive small glial cells were scattered within the cerebral cortical plate and the striatum already at PND 1, GDNF expression among astroglial cells within the corpus callosum and in the white matter adjacent to the lateral ventricles was more prominent between PND 5 and 8. GDNF expression among the pyramidal neurons of the cerebral cortex was evident relatively early in the postnatal period, but the neurons of the hippocampus and thalamus showed more intense immunoreactivity at later periods between PND 8–14. ELISA of the CSF revealed a rapid rise in GDNF levels from 71.4±10.9pg/ml (mean±S.E.M.) at PND 1 to peak levels of 138.4±18.5, 135.1±5.4 and 132.9±8.0pg/ml, at PND 5, 7 and 9, respectively. Peak CSF levels of GDNF occurred when GDNF expression was intense within astroglial cells in the corpus callosum and cerebral white matter. Thereafter, the levels gradually decreased to 76.5±9.7pg/ml at PND 21. The widespread expression of GDNF among different cellular elements in the developing brain suggest that GDNF probably plays diverse functional roles in many different neuronal systems in addition to its known effects on the dopaminergic system. Developmental shifts in GDNF expression further suggest that GDNF may be of critical importance at different stages of brain growth and differentiation.