Trophic factors counteract elevated FGF-2-induced inhibition of adult neurogenesis.
The dentate gyrus of adult mammalian brain contains neural progenitor cells with self-renewal and multi-lineage potential. The lineage and maturation of the neural progenitors are determined by the composition and levels of the trophic factors in their microenvironment. In Alzheimer disease (AD) brain, especially the hippocampus, the level of basic fibroblast growth factor (FGF-2) is markedly elevated. Here we show that elevated FGF-2 enhances the division and nestin levels of cultured adult rat hippocampal progenitors but impairs neuronal lineage determination and maturation of these cells in culture. The trophic factors ciliary neurotrophic factor (CNTF), glial-derived neurotrophic factor (GDNF), and insulin-like growth factors-1 and -2 (IGF-1, IGF-2) as well as an Alzheimer peptidergic drug, Cerebrolysin((R)) (CL), in which we found these neurotrophic activities, counteract the effect of FGF-2 in inducing neuronal lineage (early neurogenesis). Whereas CNTF is the most active of the neurotrophic factors studied in promoting neurogenesis, CL, probably because of a combined effect of these factors, induces similar changes but without inhibiting cell proliferation. These findings suggest that CNTF, GDNF, IGF-1, and IGF-2 are promising therapeutic targets for AD and other diseases in which neurogenesis is probably inhibited.
Chen
Honghui
H
New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314-6399, USA. honghui@hotmail.com
Tung
Yunn-Chyn
YC
Li
Bin
B
Iqbal
Khalid
K
Grundke-Iqbal
Inge
I
D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000276:immunology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects*
D000596:Amino Acids; D000906:Antibodies; D007381:Intermediate Filament Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D016222:Fibroblast Growth Factor 2; C006952:cerebrolysin; D001973:Bromodeoxyuridine