Affiliations: Department of Neurosurgery, University of Bern, Bern,
Switzerland | Department of Physiology and Zoology, University of
Seville, Seville, Spain | Department of Anatomy and Neurobiology, University of
Southern Denmark, Odense, Denmark
Note: [] Corresponding author: Hans R. Widmer, Ph.D. Dept. of
Neurosurgery University of Bern CH-3010 Bern Switzerland. Tel.: +41 31 632
2770; Fax: +41 31 382 2414; E-mail: hanswi@insel.ch
Abstract: Purpose: To analyze the effects of CGP 3466, a compound structurally
related to deprenyl, on survival and function of fetal ventral mesencephalic
dopaminergic neurons. Methods: 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. Results: 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. Conclusions: 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.
