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

被引:222
作者
Åberg, MAI
Åberg, ND
Palmer, TD
Alborn, AM
Carlsson-Skwirut, C
Bang, P
Rosengren, LE
Olsson, T
Gage, FH
Eriksson, PS
机构
[1] Univ Gothenburg, Sahlgrens Univ Hosp, Inst Clin Neurosci, Arvid Carlsson Inst Neurosci, SE-41345 Gothenburg, Sweden
[2] Stanford Univ, Med Ctr, Dept Neurosurg, MSLS, Palo Alto, CA 94304 USA
[3] Karolinska Hosp, Astrid Lindgrens Childrens Hosp, Pediat Endocrinol Unit, SE-17176 Stockholm, Sweden
[4] Chalmers Univ Technol, Dept Signals & Syst, S-41296 Gothenburg, Sweden
[5] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA
关键词
brain; rat; IGF-I; insulin-like growth factor-I; stem cell; progenitor cell; hippocampus; neurogenesis; MAPK; mitogen-activated protein kinase; P13-K; IGFBP;
D O I
10.1016/S1044-7431(03)00082-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:23 / 40
页数:18
相关论文
共 65 条
[1]  
Åberg MAI, 2000, J NEUROSCI, V20, P2896
[2]   Early stimulation and late inhibition of extracellular signal-regulated kinase 1/2 phosphorylation by IGF-I: A potential mechanism mediating the switch in IGF-I action on skeletal muscle cell differentiation [J].
Adi, S ;
Bin-Abbas, B ;
Wu, NY ;
Rosenthal, SM .
ENDOCRINOLOGY, 2002, 143 (02) :511-516
[3]   BRAIN NEURONS DEVELOP IN A SERUM AND GLIAL FREE ENVIRONMENT - EFFECTS OF TRANSFERRIN, INSULIN, INSULIN-LIKE GROWTH FACTOR-I AND THYROID-HORMONE ON NEURONAL SURVIVAL, GROWTH AND DIFFERENTIATION [J].
AIZENMAN, Y ;
DEVELLIS, J .
BRAIN RESEARCH, 1987, 406 (1-2) :32-42
[4]   PD-098059 IS A SPECIFIC INHIBITOR OF THE ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE KINASE IN-VITRO AND IN-VIVO [J].
ALESSI, DR ;
CUENDA, A ;
COHEN, P ;
DUDLEY, DT ;
SALTIEL, AR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (46) :27489-27494
[5]   AUTORADIOGRAPHIC AND HISTOLOGICAL EVIDENCE OF POSTNATAL HIPPOCAMPAL NEUROGENESIS IN RATS [J].
ALTMAN, J ;
DAS, GD .
JOURNAL OF COMPARATIVE NEUROLOGY, 1965, 124 (03) :319-&
[6]  
Arsenijevic Y, 1998, J NEUROSCI, V18, P2118
[7]   Insulin-like growth factor-1 is necessary for neural stem cell proliferation and demonstrates distinct actions of epidermal growth factor and fibroblast growth factor-2 [J].
Arsenijevic, Y ;
Weiss, S ;
Schneider, B ;
Aebischer, P .
JOURNAL OF NEUROSCIENCE, 2001, 21 (18) :7194-7202
[8]   INCREASED PROTEOLYSIS OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-3 (IGFBP-3) IN NONINSULIN-DEPENDENT DIABETES-MELLITUS SERUM, WITH ELEVATION OF A 29-KILODALTON (KDA) GLYCOSYLATED IGFBP-3 FRAGMENT CONTAINED IN THE APPROXIMATELY 130-KDA TO 150-KDA TERNARY COMPLEX [J].
BANG, P ;
BRISMAR, K ;
ROSENFELD, RG .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1994, 78 (05) :1119-1127
[9]   COMPARISON OF ACID ETHANOL EXTRACTION AND ACID GEL-FILTRATION PRIOR TO IGF-I AND IGF-II RADIOIMMUNOASSAYS - IMPROVEMENT OF DETERMINATIONS IN ACID ETHANOL EXTRACTS BY THE USE OF TRUNCATED IGF-I AS RADIOLIGAND [J].
BANG, P ;
ERIKSSON, U ;
SARA, V ;
WIVALL, IL ;
HALL, K .
ACTA ENDOCRINOLOGICA, 1991, 124 (06) :620-629
[10]   IGF1 GENE DISRUPTION RESULTS IN REDUCED BRAIN SIZE, CNS HYPOMYELINATION, AND LOSS OF HIPPOCAMPAL GRANULE AND STRIATAL PARVALBUMIN-CONTAINING NEURONS [J].
BECK, KD ;
POWELLBRAXTON, L ;
WIDMER, HR ;
VALVERDE, J ;
HEFTI, F .
NEURON, 1995, 14 (04) :717-730