Glial cell line-derived neurotrophic factor-like immunoreactivity in the cerebella of normal subjects and patients with multiple system atrophy.

Abstract

Glial cell line-derived neurotrophic factor (GDNF) has a trophic effect on various types of neurons, including cerebellar Purkinje cells. To investigate the role of GDNF in the human cerebellum, we examined the cerebella of eight control cases and eight patients with multiple system atrophy (MSA) immunohistochemically using a polyclonal anti-GDNF antibody. The antibody recognized a single band of approximately 34 kDa on Western blot analysis of human cerebellar homogenates. In the cerebella from normal subjects, the neuronal somata and dendrites of the Purkinje cells were immunostained intensely, as were some axons, including torpedoes, immunolabeled in the granular layer. Many axons and a few oligodendrocytes were also immunopositive in the white matter, and weak immunoreactivity was detected in the granule cells and neurons in the cerebellar nuclei. In the cerebella from patients with MSA, the general immunostaining pattern was similar to that observed in the normal subjects. Most of the remaining Purkinje cells showed strong immunoreactivity, and abundant GDNF-positive granular structures or dense arborizations of GDNF-positive dendrites were found in some areas of the molecular layer. These data suggest that GDNF may be mainly produced and localized in the Purkinje cells of the human cerebellum, even in patients with MSA, and that the functional impairment of the Purkinje cells of MSA patients might cause a focal accumulation of GDNF in the dendrites of some of the surviving Purkinje cells.