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Titolo:
Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation
Autore:
Ma, W; Maric, D; Li, BS; Hu, Q; Andreadis, JD; Grant, GM; Liu, QY; Shaffer, KM; Chang, YH; Zhang, L; Pancrazio, JJ; Pant, HC; Stenger, DA; Barker, JL;
Indirizzi:
USN, Ctr Biomol Sci & Engn, Res Lab, Washington, DC 20375 USA USN Washington DC USA 20375 Sci & Engn, Res Lab, Washington, DC 20375 USA NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA NINDS Bethesda MD USA 20892 Neurophysiol Lab, NIH, Bethesda, MD 20892 USA NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA NINDS Bethesda MD USA 20892 S, Neurochem Lab, NIH, Bethesda, MD 20892 USA
Titolo Testata:
EUROPEAN JOURNAL OF NEUROSCIENCE
fascicolo: 4, volume: 12, anno: 2000,
pagine: 1227 - 1240
SICI:
0953-816X(200004)12:4<1227:ASCPCP>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
STEM-CELLS; OLIGODENDROCYTE PROGENITORS; CHOLINERGIC NEURONS; PROTEIN-KINASE; GROWTH-FACTORS; RAT-BRAIN; EXPRESSION; MITOGEN; NEUROTRANSMITTERS; SUBUNITS;
Keywords:
Ca2+ imaging; neural stem cell; neurogenesis; rat; signal transduction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Ma, W USN, Ctr Biomol Sci & Engn, Res Lab, Washington, DC 20375 USA USN Washington DC USA 20375 Engn, Res Lab, Washington, DC 20375 USA
Citazione:
W. Ma et al., "Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation", EUR J NEURO, 12(4), 2000, pp. 1227-1240

Abstract

Increasing evidence has shown that some neurotransmitters act as growth-regulatory signals during brain development. Here we report a role for the classical neurotransmitter acetylcholine (ACh) to stimulate proliferation of neural stem cells and stem cell-derived progenitor cells during neural celllineage progression in vitro. Neuroepithelial cells in the ventricular zone of the embryonic rat cortex were found to express the m2 subtype of the muscarinic receptor. Neural precursor cells dissociated from the embryonic rat cortical neuroepithelium were expanded in culture with basic fibroblast growth factor (bFGF). reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of m2, m3 and m4 muscarinic receptor subtype transcripts, while immunocytochemistry demonstrated m2 protein. ACh and carbachol induced an increase in cytosolic Ca2+ and membrane currents in proliferating (BrdU(+)) cells, both of which were abolished by atropine. Exposure ofbFGF-deprived precursor cells to muscarinic agonists not only increased both cell number and DNA synthesis, but also enhanced differentiation of neurons. These effects were blocked by atropine, indicating the involvement of muscarinic ACh receptors. The growth-stimulating effects were also antagonized by a panel of inhibitors of second messengers, including 1,2-bis-(O-aminophenoxy)-ethane-N, N, N',N'-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, EGTA to complex extracellular Ca2+, pertussis toxin, which uncouples certain G-proteins, the protein kinase C inhibitor H7 and the mitogen-activated protein kinase (MAPK) inhibitor PD98059. Muscarinic agonists activated MARK, which was significantly inhibited by atropine and the same panelof inhibitors. Thus, muscarinic receptors expressed by neural precursors transduce a growth-regulatory signal during neurogenesis via pathways involving pertussis toxin-sensitive G-proteins, Ca2+ signalling, protein kinase Cactivation, MAPK phosphorylation and DNA synthesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 22:34:59