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Cited by 161Neurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology ResearchDevelopmental Biology and Gene Regulation

Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation

Ma, Wu, Maric, Dragan, Li, Bing‐sheng, Hu, Qian, Andreadis, Joanne D., Grant, Geraldine M., Liu, Qi‐Ying, Shaffer, Kara M. +6 more·2000·European Journal of Neuroscience
DOI 10.1046/j.1460-9568.2000.00010.x
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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 cell lineage 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 Ca 2+ and membrane currents in proliferating (BrdU+) cells, both of which were abolished by atropine. Exposure of bFGF‐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 Ca 2+, EGTA to complex extracellular Ca 2+, 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 MAPK, which was significantly inhibited by atropine and the same panel of inhibitors. Thus, muscarinic receptors expressed by neural precursors transduce a growth‐regulatory signal during neurogenesis via pathways involving pertussis toxin‐sensitive G‐proteins, Ca 2+ signalling, protein kinase C activation, MAPK phosphorylation and DNA synthesis.

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  • Even before the cholinergic projections arrive in the cortical areas, the nicotinic and muscarinic receptors are expressed on neural progenitors, playing a role in proliferation/differentiation and axonal guidance events.

    “But even before the cholinergic projections arrive in the cortical areas, the nicotinic and muscarinic receptors are expressed on neural progenitors playing a role in proliferation/differentiation and axonal guidance events [214–217].”

    From Development of prefrontal cortex (2022) · cites this paper as [216]

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Authors
Ma, W., Maric, D., Li, B., Hu, Q., Andreadis, J. D., Grant, G. M., Liu, Q., Shaffer, K. M., Chang, Y. H., Zhang, L., Pancrazio, J. J., Pant, H. C., Stenger, D. A., & Barker, J. L.
Affiliations
  • United States Naval Research Laboratory (US)
  • National Institutes of Health (US)
ORCID
Venue
European Journal of Neuroscience
Publisher
Wiley
Published
2000-04
Volume
12
Issue
4
Pages
1227-1240
ISSN
  • 0953-816X (ISSN-L)
  • 1460-9568
DOI
10.1046/j.1460-9568.2000.00010.x
OpenAlex
W1508623490
Cited by
161
References
39
Citations by year
2026: 1 · 2023: 1 · 2022: 6 · 2021: 1 · 2019: 7 · 2018: 8 · 2017: 3 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 4 · 2012: 3
FWCI
2.52
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 632 d)
Locations
  • European Journal of Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (7r21aa012237-02)
  • National Institute on Alcohol Abuse and Alcoholism (R21AA12237-02)
  • U.S. Naval Research Laboratory
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
acetylcholine, muscarinic receptors, M2 muscarinic receptor, neural progenitor cells, cell proliferation, MAPK phosphorylation, protein kinase C, calcium signaling, G proteins, neurogenesis, carbachol, atropine, basic fibroblast growth factor, neuronal differentiation
MeSH terms
Acetylcholine, Animals, Atropine, Bromodeoxyuridine, Calcium, Cell Division, Cells, Cultured, Cerebral Cortex, Female, Muscarine, Neurons, Virulence Factors, Bordetella, Phosphorylation, Pregnancy, Protein Kinase C, Receptors, Muscarinic, Stem Cells, Thymidine, Tritium, Vasodilator Agents, Fibroblast Growth Factor 2, Rats, Sprague-Dawley, Patch-Clamp Techniques, Muscarinic Agonists, Muscarinic Antagonists, GTP-Binding Proteins, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Pertussis Toxin, Receptor, Muscarinic M2, Receptor, Muscarinic M3, Receptor, Muscarinic M4, Rats

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