title: Glucocorticoids dexamethasone and hydrocortisone inhibit proliferation and accelerate maturation of chicken cerebellar granule neurons.
abstract: Glucocorticoid (GC) treatment in premature infants may have detrimental effects on the immature brain. Here we show that GCs dexamethasone (Dex) and hydrocortisone (HC) reduce proliferation and induce differentiation of chicken embryo cerebellar neurons in vivo and in vitro. Granule neurons incorporating bromodeoxyuridine were reduced in the internal granular layer (IGL) after 24-h exposure to both substances on embryonic day 17, with Dex about 100-fold more potent than HC. The effects were blocked by GR antagonist RU 38486. Both GCs also increased the expression of neuronal differentiation markers microtubule-associated protein 2 (Map2) and neuronal nuclei protein (NeuN), measured by western blotting of whole cerebellar lysates and immunohistochemistry, respectively. Treatment of cerebellar granule neuron cultures with both GCs significantly reduced the percentage of proliferating-cell nuclear antigen (PCNA) positive neurons and increased NeuN positive neurons, with similar dose-response relationship as in vivo. The cytostatic agent cytosine arabinoside showed comparable effects both on proliferation and differentiation. In conclusion, the effects of Dex and HC on chicken cerebellar granule neuron proliferation are GR mediated and reflect their pharmacological potency. In addition, the effects on differentiation may be related to a cell cycle block per se, since cytosine arabinoside mimicked the effect of the GCs.
authors.affiliation: Department of Pathology, Oslo University Hospital, Ullevål, Norway. petra.aden@oslo-universitetssykehus.no
authors.forename: Petra
authors.initials: P
authors.lastname: Aden
authors.forename: Ragnhild E
authors.initials: RE
authors.lastname: Paulsen
authors.forename: Jan
authors.initials: J
authors.lastname: Mæhlen
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Løberg
authors.forename: Ingeborg L
authors.initials: IL
authors.lastname: Goverud
authors.forename: Knut
authors.initials: K
authors.lastname: Liestøl
authors.forename: Jon
authors.initials: J
authors.lastname: Lømo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D002642:Chick Embryo / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D006727:Hormone Antagonists; D008869:Microtubule-Associated Proteins; D018809:Proliferating Cell Nuclear Antigen; D015735:Mifepristone; D003907:Dexamethasone; D001973:Bromodeoxyuridine; D006854:Hydrocortisone