title: Dexamethasone inhibits the maturation of newly formed neurons and glia supplemented with polyunsaturated fatty acids.
abstract: Stress bears a negative impact on adult neurogenesis. High levels of corticoids have been shown to inhibit neural stem cell proliferation, and are considered responsible for the loss of neural precursors. Their effects on the differentiation of the glial and neuronal lineages have been less studied. We examined the effect of dexamethasone (Dex), a synthetic glucocorticoid, on the differentiation of rat neural stem cells in vitro. Dex had no effect on the differentiation of cells cultured under standard conditions. Since we previously determined that NSC, when cultured under classical conditions, were deprived of polyunsaturated fatty acids (PUFA), and displayed phospholipid compositions very different from the in vivo figures [1], we examined the effect of Dex under PUFA supplementation. Dex impaired neuron and oligodendrocyte maturation in PUFA-supplemented cells, demonstrated by the reduction of neurite lengths and oligodendrocyte sizes. This effect was mediated by the glucocorticoid receptor (GR), since it was eliminated by mifepristone, a GR antagonist, and could be relayed by a reduction of ERK phosphorylation. We determined that GR was associated with PPAR β and α under basal conditions, and that this association was disrupted when PUFA were added in combination with Dex. We assumed that this effect on the receptor status enabled the effect of Dex on PUFA supplemented cells, since we determined that the binding to the glucocorticoid response element was higher in cells incubated with PUFA and Dex. In conclusion, corticoids can impair NSC differentiation, and consequently impact the entire process of neurogenesis.
authors.affiliation: INRA UR0909 Laboratoire de Nutrition et Régulations Lipidiques des Fonctions Cérébrales, CRJ 78352 Jouy-en-Josas, France. Electronic address: Christine.Heberden@jouy.inra.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Heberden
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Meffray
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Goustard-Langelier
authors.forename: Elise
authors.initials: E
authors.lastname: Maximin
authors.forename: Monique
authors.initials: M
authors.lastname: Lavialle
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D047468:Immunoprecipitation; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005231:Fatty Acids, Unsaturated; D003907:Dexamethasone
keywords: Glucocorticoid; Neural stem cells; Nuclear receptor