IGF-I has a direct proliferative effect in adult hippocampal progenitor cells.

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

1-Phosphatidylinositol 3-Kinase

drug effects

metabolism

Animals

Cell Differentiation

drug effects

physiology

Cell Division

drug effects

physiology

Cell Lineage

drug effects

physiology

Cells

Cultured

Dose-Response Relationship

Drug

Fibroblast Growth Factor 2

metabolism

pharmacology

Hippocampus

cytology

drug effects

growth & development

Insulin-Like Growth Factor Binding Proteins

drug effects

metabolism

Insulin-Like Growth Factor I

metabolism

pharmacology

MAP Kinase Signaling System

drug effects

physiology

Rats

Receptor

IGF Type 1

drug effects

metabolism

Ribosomal Protein S6 Kinases

70-kDa

drug effects

metabolism

Signal Transduction

drug effects

physiology

Stem Cells

cytology

drug effects

metabolism

Thymidine

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)