Striatal extracts promote the survival and phenotypic expression of rat fetal dopaminergic neurons in vitro

To begin to identify novel protein(s) that acts on nigral dopaminergic (DA) neurons, we characterized trophic effects of DA-depleted striatum on survi val of fetal DA neurons in the present study. Treatment of ventral mesencep halic cultures with the striatal extracts delayed DA cell death in a dose-d ependent manner. This effect was partially dependent on brain-derived neuro trophic factor (BDNF), but not glial cell line-derived neurotrophic factor (GDNF), present in the extracts. Furthermore, we addressed the hypothesis t hat the striatum-derived substances can elicit DA phenotypic expression of striata I cells in cu Itu res. The striatal extract was found to be able to induce expression of tyrosine hydroxylase in cu Itu red striatal cells in the presence of dopamine. These data suggest that denervation of the striat um resulted in production of neurotrophic factors, including BDNF and as-ye t-unidentified trophic substances, which may be responsible for the increas ed survival and DA phenotype expression in DA neurons. (C) 2000 Elsevier Sc ience Ireland Ltd. All rights reserved.