Brain-derived neurotrophic factor selectively rescues mesencephalic dopaminergic neurons from 2,4,5-trihydroxyphenylalanine-induced injury.
Brain-derived neurotrophic factor (BDNF) supports the survival of sensory neurons as well as retinal ganglion cells, basal forebrain cholinergic neurons, and mesencephalic dopaminergic neurons in vitro. Here we examined the ability of BDNF to confer protection on cultured dopaminergic neurons against the neurotoxic effects of 6-hydroxyDOPA (TOPA or 2,4,5-trihydroxyphenylalanine), a metabolite of the dopamine pathway suggested to participate in the pathology of Parkinson's disease. Cells prepared from embryonic day 14-15 rat mesencephalon were maintained with 10-50 ng/ml BDNF for 7 days prior to addition of TOPA (10-30 microM) for 24 hr. In BDNF-treated cultures, the extensive loss (> 90%) of tyrosine hydroxylase immunopositive cells was virtually (< 10%) eliminated, while the equally drastic loss (> 90%) of the overall cell population was limited to only a 25-30% recovery. Furthermore, the monosialoganglioside GM1 (1-10 microM), although inactive alone, acted synergistically with subthreshold amounts of BDNF to rescue tyrosine hydroxylase-positive cells against TOPA neurotoxicity. These results add impetus to exploring the therapeutic potential of gangliosides and BDNF in Parkinson's disease.
Skaper
S D
SD
Fidia Research Laboratories, Fidia S.p.A., Abano Terme, Italy.
Negro
A
A
Facci
L
L
Dal Toso
R
R
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D004298:Dopamine / Q000502:physiology*; D005260:Female; D005677:G(M1) Ganglioside / Q000096:biosynthesis; D008636:Mesencephalon / Q000166:cytology*; D009410:Nerve Degeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C001388:6-hydroxydopa; D005677:G(M1) Ganglioside; D005680:gamma-Aminobutyric Acid; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine