Dexamethasone blocks astroglial differentiation from neural precursor cells.
In previous studies, we demonstrated functional neuronal and dopaminergic differentiation of fetal mesencephalic neural precursor cells. The major factors for orienting their progeny towards a dopaminergic phenotype are forskolin and interleukin-1beta. Here, we investigated the effects of dexamethasone (10 microM) on neuronal and glial differentiation. Exposure of mesencephalic neural precursor cells to dexamethasone significantly reduces the amount of glial fibrillary acidic protein astroglia, but not of galactocerebrosidase C oligodendroglia, MAP2ab neurons and tyrosine hydroxylase dopaminergic cells. Presuming a possible involvement of the nuclear factor-kappaB pathway, we examined the effects of wortmannin (phosphatidylinositol 3'-kinase inhibitor) and SN50 (nuclear factor-kappaB inhibitor) on gliogenesis. Both wortmannin and SN50 mimicked the effects of dexamethasone suggesting that dexamethasone specifically blocks astroglial differentiation from mesencephalic neural precursor cells most likely via inhibition of the nuclear factor-kappaB pathway.
Sabolek
Michael
M
Department of Neurology, University of Ulm, Ulm, Germany.
Herborg
Anna
A
Schwarz
Johannes
J
Storch
Alexander
A
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005938:Glucocorticoids / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
D005938:Glucocorticoids; D053583:Interleukin-1beta; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D003907:Dexamethasone; D004298:Dopamine