GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR (GDNF) GENE-EXPRESSION INTHE HUMAN BRAIN - A POST-MORTEM IN-SITU HYBRIDIZATION STUDY WITH SPECIAL REFERENCE TO PARKINSONS-DISEASE

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotr ophic factor for dopaminergic neurons. Since dopaminergic neurons dege nerate in Parkinson's disease, this factor is a potential therapeutica l tool that may save dopaminergic neurons during the pathological proc ess. Moreover, a reduced GDNF expression may be involved in the pathop hysiology of the disease. In this study, we tested whether altered GDN F production may participate in the mechanism of cell death in this di sease. GDNF gene expression was analyzed by in situ hybridization usin g riboprobes corresponding to a sequence of the exon 2 human GDNF gene . Experiments were performed on tissue sections of the mesencephalon a nd the striatum from 8 patients with Parkinson's disease and 6 control subjects matched for age at death and for post mortem delay. No label ling was observed in either group of patients. This absence of detecta ble expression could not be attributed to methodological problems as a positive staining was observed using the same probes for sections of astroglioma biopsies from human adults and for sections of a newborn i nfant brain obtained at post-mortem These data suggest that GDNF is pr obably expressed at a very low level in the adult human brain and its involvement in the pathophysiology of Parkinson's disease remains to b e demonstrated. GDNF may represent a powerful new therapeutic agent fo r Parkinson's disease, however.