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M2 muscarinic receptor activation regulates Schwann cell differentiation and myelin organization.
- Source :
-
Developmental neurobiology [Dev Neurobiol] 2014 Jul; Vol. 74 (7), pp. 676-91. Date of Electronic Publication: 2014 Jan 09. - Publication Year :
- 2014
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Abstract
- Glial cells express acetylcholine receptors. In particular, rat Schwann cells express different muscarinic receptor subtypes, the most abundant of which is the M2 subtype. M2 receptor activation causes a reversible arrest of the cell cycle. This negative effect on Schwann cell proliferation suggests that these cells may possibly progress into a differentiating program. In this study we analyzed the in vitro modulation, by the M2 agonist arecaidine, of transcription factors and specific signaling pathways involved in Schwann cell differentiation. The arecaidine-induced M2 receptor activation significantly upregulates transcription factors involved in the promyelinating phase (e.g., Sox10 and Krox20) and downregulates proteins involved in the maintenance of the undifferentiated state (e.g., c-jun, Notch-1, and Jagged-1). Furthermore, arecaidine stimulation significantly increases the expression of myelin proteins, which is accompanied by evident changes in cell morphology, as indicated by electron microscopy analysis, and by substantial cellular re-distribution of actin and cell adhesion molecules. Moreover, ultrastructural and morphometric analyses on sciatic nerves of M2/M4 knockout mice show numerous degenerating axons and clear alterations in myelin organization compared with wild-type mice. Therefore, our data demonstrate that acetylcholine mediates axon-glia cross talk, favoring Schwann cell progression into a differentiated myelinating phenotype and contributing to compact myelin organization.<br /> (© 2013 Wiley Periodicals, Inc.)
- Subjects :
- Animals
Arecoline analogs & derivatives
Arecoline pharmacology
Axons drug effects
Axons physiology
Axons ultrastructure
Cells, Cultured
Mice, Knockout
Myelin Proteins metabolism
Myelin Sheath drug effects
Myelin Sheath ultrastructure
Nerve Degeneration pathology
Nerve Degeneration physiopathology
Peripheral Nervous System Agents pharmacology
RNA, Messenger genetics
RNA, Messenger metabolism
Rats, Wistar
Receptor, Muscarinic M2 agonists
Receptor, Muscarinic M2 genetics
Receptor, Muscarinic M4 genetics
Receptor, Muscarinic M4 metabolism
Schwann Cells drug effects
Schwann Cells ultrastructure
Sciatic Nerve drug effects
Sciatic Nerve physiology
Sciatic Nerve physiopathology
Sciatic Nerve ultrastructure
Signal Transduction drug effects
Transcription Factors metabolism
Myelin Sheath physiology
Neurogenesis drug effects
Receptor, Muscarinic M2 metabolism
Schwann Cells physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-846X
- Volume :
- 74
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Developmental neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 24403178
- Full Text :
- https://doi.org/10.1002/dneu.22161