Molecules with neurotrophic effects on the human developing mesencephalic dopaminergic neurons.
Parkinson's disease (PD) is characterized by the degeneration of the mesencephalic dopaminergic (mesDA) neurons innervating the striatum. Neurotrophic factor(s) that prevents the degeneration and increases the functional activity of the remaining mesDA neurons are of substantial clinical interest. The origin and development of mesDA neurons were characterized in the human mesencephalon from 5.0 to 12 Postconception (PC) weeks. Tyrosine Hydroxylase (TH) immunoreactive cells were first demonstrated at 5.5 PC weeks next to the ventricular zone. In primary culture, TH immunoreactive neurons represent 3 to 5% of the total cells at days 7 in vitro and basic Fibroblast growth factor (bFGF) was demonstrated to induce a significant increase of both TH immunoreactive cell number and TH enzymatic activity. This effect was mediated by proliferating glial fibrillary acidic protein immunoreactive cells. Nerve growth factor treatment did not have any appreciable effect. The effect of bFGF on TH positive cells described in this human bioassay is only a preliminary evidence that, if confirmed by experiments in vivo, may provide a starting rationale for investigating alternative strategies in the treatment of PD.
Silani
V
V
Institute of Neurology, University of Milan Medical School, Italy.
Bernasconi
S
S
Pizzuti
A
A
Sampietro
A
A
Brioschi
A
A
Buscaglia
M
M
Scarlato
G
G
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D009414:Nerve Growth Factors; D016222:Fibroblast Growth Factor 2; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine