CGP 3466 increases survival of cultured fetal dopaminergic neurons

To analyze the effects of CGP 3466, a compound structurally related to deprenyl, on survival and function of fetal ventral mesencephalic dopaminergic neurons.

Free-floating roller tube (FFRT) cultures of rat (E14) ventral mesencephalon were treated with CGP 3466 [10-8 M] for 7 days. Tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) immunocytochemistry was performed to allow analysis of dopaminergic neurons and astroglial cells, respectively. Lactate dehydrogenase activity in the culture medium served as a measure of cell death. Control and CGP 3466 treated cultures were grafted into 6-hydroxydopamine-lesioned rats, and graft survival and function evaluated 9 weeks posttransplantation.

FFRT cultures treated with CGP 3466 contained significantly more (two fold) surviving TH-immunoreactive (-ir) neurons and decreased lactate dehydrogenase activity in the culture medium compared to controls. The actions of CGP 3466 seem not to be mediated by astroglial cells, since GFAP-ir cell numbers and GFAP protein levels did not differ between the groups. CGP 3466 pretreatment of donor cultures did not improve TH-ir cell survival in the grafts nor did it alter functional recovery as compared to controls.

CGP 3466 is an effective survival factor for cultured midbrain dopaminergic neurons. However, CGP 3466 pretreatment does not ameliorate survival and function of the dopaminergic neurons after grafting into a rat model of Parkinson's disease.