Progenitor cells from the adult mouse brain acquire a neuronal phenotype in response to beta-amyloid.
Neurospheres from adult mouse subventricular zone (SVZ) were grown in suspension cultures for 12-15 days. Neurospheres consisted mainly of neural precursor cells (NPCs) immunoreactive for nestin and also contained nestin-negative precursors. We used these neurospheres to determine the effects of synthetic beta-amyloid fragments (both betaAP(1-42) and betaAP(25-35)) on NPC proliferation, differentiation and survival. We show that neurospheres exposed to 25 microM betaAP(25-35) or betaAP(1-42) for 24 h (a toxic condition for mature neurons) did not undergo apoptosis. Instead, betaAP(25-35) orientated nestin-negative precursors towards nestin-positive NPCs and turned nestin-positive NPCs into neuroblasts. Intracerebroventricular infusion of full-length betaAP(1-42) increased the population of PSA-NCAM-positive cells in the SVZ, without affecting proliferation. We conclude that betaAP influences the fate of progenitor cells, driving their differentiation towards a neuronal lineage.
Calafiore
M
M
Department of Pharmaceutical Sciences, University of Catania, Catania 95125, Italy.
Battaglia
G
G
Zappalà
A
A
Trovato-Salinaro
E
E
Caraci
F
F
Caruso
M
M
Vancheri
C
C
Sortino
M A
MA
Nicoletti
F
F
Copani
A
A
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D010641:Phenotype; D012794:Sialic Acids / Q000378:metabolism; D013234:Stem Cells
D016229:Amyloid beta-Peptides; D000954:Antigens, Surface; D051927:CD24 Antigen; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1; D010446:Peptide Fragments; D012794:Sialic Acids; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); C103469:polysialyl neural cell adhesion molecule; C092261:antigen Dlx-2; D001973:Bromodeoxyuridine