title: IGF-I has a direct proliferative effect in adult hippocampal progenitor cells.
abstract: The aim of the present study was to investigate the potential direct effects of insulin-like growth factor-I (IGF-I) on adult rat hippocampal stem/progenitor cells (AHPs). IGF-I-treated cultures showed a dose-dependent increase in thymidine incorporation, total number of cells, and number of cells entering the mitosis phase. Pretreatment with fibroblast growth factor-2 (FGF-2) increased the IGF-I receptor (IGF-IR) expression, and both FGF-2 and IGF-I were required for maximal proliferation. Time-lapse recordings showed that IGF-I at 100 ng/ml decreased differentiation and increased proliferation of single AHPs. Specific inhibition of mitogen-activated protein kinase kinase (MAPKK), phosphatidylinositol 3-kinase (PI3-K), or the downstream effector of the PI3-K pathway, serine/threonine p70 S6 kinase (p70(S6K)), showed that both the MAPK and the PI3-K pathways participate in IGF-I-induced proliferation but that the MAPK activation is obligatory. These results were confirmed with dominant-negative constructs for these pathways. Stimulation of differentiation was found at a low dose (1 ng/ml) of IGF-I, clonal analysis indicating an instructive component of IGF-I signaling.
authors.affiliation: The Arvid Carlsson Institute for Neuroscience at the Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Göteborg University, Blå Stråket 7, SE-413 45 Göteborg, Sweden.
authors.forename: Maria A I
authors.initials: MA
authors.lastname: Aberg
authors.forename: N David
authors.initials: ND
authors.lastname: Aberg
authors.forename: Theo D
authors.initials: TD
authors.lastname: Palmer
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Alborn
authors.forename: Christine
authors.initials: C
authors.lastname: Carlsson-Skwirut
authors.forename: Peter
authors.initials: P
authors.lastname: Bang
authors.forename: Lars E
authors.initials: LE
authors.lastname: Rosengren
authors.forename: Torsten
authors.initials: T
authors.lastname: Olsson
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.forename: Peter S
authors.initials: PS
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D013936:Thymidine