Human astrocytes can be induced to differentiate into cells with neuronal phenotype.
Several recent studies have proposed that astrocytes may contribute to neurogenesis, not only as a source of trophic substances regulating it, but also as stem cells themselves. In order to better understand these mechanisms, primary astrocyte cultures were established from human fetal brain. After 3-4 weeks in culture, astrocytes (about 95% GFAP+; neurofilament, NF-; neuro-specific enolase, NSE-) were treated with a cocktail of protein kinase activators and FGF-1. After 5 h of treatment, most cells showed morphological changes that increased progressively up to 24-48 h, exhibiting a round cell body with long processes. Immunocytochemistry showed that treatment-induced NF and NSE expression in about 40% of cells. Nestin expression increased after treatment, whereas GFAP immunostaining was not significantly modified. Western blot and RT-PCR confirmed the results. No neuronal electrophysiological properties were observed after treatment, suggesting an incomplete maturation under these experimental conditions. Understanding the regenerative capability and neurogenic potential of astrocytes might be useful in devising therapeutic approaches for a variety of neurological disorders.
Pillai
Rita
R
Department of Cytomorphology, University of Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
Scintu
Franca
F
Scorciapino
Laura
L
Carta
Mario
M
Murru
Luca
L
Biggio
Giovanni
G
Cabras
Stefano
S
Reali
Camilla
C
Sogos
Valeria
V
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D005333:Fetus; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D015870:Gene Expression / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000072056:Transcription Factor HES-1; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
D015056:1-Methyl-3-isobutylxanthine; D051792:Basic Helix-Loop-Helix Proteins; D005576:Colforsin; D016220:Fibroblast Growth Factor 1; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D016900:Neurofilament Proteins; D010751:Phosphopyruvate Hydratase; D012333:RNA, Messenger; D016708:Synaptophysin; D013755:Tetradecanoylphorbol Acetate; D000072056:Transcription Factor HES-1; D014404:Tubulin; C577484:NES protein, human; C061195:neurofilament protein M; C078493:HES1 protein, human