Comparison of GDF5 and GDNF as neuroprotective factors for postnatal dopamine neurons in ventral mesencephalic cultures.

Abstract

Loss of dopamine neurons is associated with the motor deficits that occur in Parkinson's disease. Although many drugs have proven to be useful in the treatment of the symptoms of this disease, none has been shown to have a significant impact on the development of the disease. However, we believe that several neurotrophic factors have the potential to reduce its progression. Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β superfamily of neurotrophic factors, has been extensively studied in this regard. Less attention has been paid to growth/differentiation factor 5 (GDF5), another member of the same superfamily. This study compares GDNF and GDF5 in dissociated cultures prepared from ventral mesencephalon and in organotypic co-cultures containing substantia nigra, striatum, and neocortex. We report that both GDNF (10-500 ng/ml) and GDF5 (100-500 ng/ml) promoted the survival of dopamine neurons from the substantia nigra of postnatal rats, although GDNF was considerably more potent than GDF5. In contrast, neither factor had any significant effect on the survival of dopamine neurons from the rat ventral tegmental area. Using organotypic co-cultures, we also compared GDF5 with GDNF as chemoattractants for the innervation of the striatum and the neocortex by dopamine neurons from the substantia nigra. The addition of either GDF5 or GDNF (100-500 ng/ml) caused innervation by dopamine neurons into the cortex as well as the striatum, which did not occur in untreated cultures. Our results are consistent with similar findings suggesting that GDF5, like GDNF, deserves attention as a possible therapeutic intervention for Parkinson's disease.