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

Glial cell line-derived neurotrophic factor (GDNF) has a trophic effect on various types of neurons, including cerebellar Purkinje cells. To investiga te the role of GDNF in the human cerebellum we examined the cerebella of ei ght control cases and eight patients with multiple system atrophy (MSA) imm unohistochemically using a polyclonal anti-GDNF antibody. The antibody reco gnized a single band of approximately 34 kDa on Western blot analysis of hu man cerebellar homogenates. In the cerebella from normal subjects, the neur onal somata and dendrites of the Purkinje cells were immunostained intensel y, as were some axone, including torpedoes, immunolabeled in the granular l ayer. 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 M SA, the general immunostaining pattern was similar to that observed in the normal subjects. Most of the remaining Purkinje cells showed strong immunor eactivity, and abundant GDNF-positive granular structures or dense arboriza tions 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 survivi ng Purkinje cells.