Prion diseases, also called transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders characterized by neuronal loss, astrogliosis, and spongiform changes in the brain. It is postulated that appearance of astrogliosis may provide the neurotrophic factors to prevent or reduce neuronal cell loss in the pathogenesis of prion diseases. To investigate the role of the glial cell line-derived neurotrophic factor (GDNF), we studied the expression levels of GDNF mRNA and protein in an animal model of prion diseases. The expression levels of GDNF mRNA and protein were significantly increased in the brains of scrapie-infected mice at 100 and 160 days after inoculation with scrapie strain compared with those of control mice. In addition, we found more intensive immunoreactivity of GDNF in the brains of scrapie-infected mice, specifically in the hippocampal astrocytes, than was seen in control mice. These results suggest that GDNF participates in protection against neuronal cell loss and atrophy in neurodegenerative disorders, which may play one of the important roles in the pathogenic mechanisms of prion diseases.