Nicotinic acetylcholine receptors mediate donepezil‐induced oligodendrocyte differentiation

Osamu Imamura; Masaaki Arai; Minori Dateki; Toru Ogata; Ryuji Uchida; Hiroshi Tomoda; Kunio Takishima

doi:10.1111/jnc.13294

journal article Sep 22, 2015

Nicotinic acetylcholine receptors mediate donepezil‐induced oligodendrocyte differentiation

Osamu Imamura Masaaki Arai Minori Dateki Toru Ogata Ryuji Uchida Hiroshi Tomoda Kunio Takishima

Journal of Neurochemistry Vol. 135 No. 6 pp. 1086-1098 · Wiley

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Abstract

AbstractOligodendrocytes are the myelin‐forming cells of the central nervous system (CNS). Failure of myelin development and oligodendrocyte loss results in serious human disorders, including multiple sclerosis. Here, we show that donepezil, an acetlycholinesterase inhibitor developed for the treatment of Alzheimer's disease, can stimulate oligodendrocyte differentiation and maturation of neural stem cell‐derived oligodendrocyte progenitor cells without affecting proliferation or cell viability. Transcripts for essential myelin‐associated genes, such as PLP, MAG, MBP, CNPase, and MOG, in addition to transcription factors that regulate oligodendrocyte differentiation and myelination, were rapidly increased after treatment with donepezil. Furthermore, luciferase assays confirmed that both MAG and MBP promoters display increased activity upon donepezil‐induced oligodendrocytes differentiation, suggesting that donepezil increases myelin gene expression mainly through enhanced transcription. We also found that the increase in the number of oligodendrocytes observed following donepezil treatment was significantly inhibited by the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine, but not by the muscarinic acetylcholine receptor antagonist scopolamine. Moreover, donepezil‐induced myelin‐related gene expression was suppressed by mecamylamine at both the mRNA and protein level. These results suggest that donepezil stimulates oligodendrocyte differentiation and myelin‐related gene expression via nAChRs in neural stem cell‐derived oligodendrocyte progenitor cells.imageWe show that donepezil, a drug for the treatment of Alzheimer disease, can stimulate oligodendrocyte differentiation and maturation of oligodendrocyte progenitor cells. Transcripts for essential myelin‐associated genes, such as PLP, MAG, MBP, CNPase and MOG in addition to transcripton factors that regulate oligodendrocyte differentiation and myelination were rapidly increased after treatment with donepezil. These effects were partly dependent on nicotinic acetylcholine receptor (nAChR).

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Citations

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References

Details

Published: Sep 22, 2015
Vol/Issue: 135(6)
Pages: 1086-1098
License: View

Authors

O

Osamu Imamura

Department of Biochemistry National Defense Medical College Tokorozawa Saitama Japan

M

Masaaki Arai

Department of Biochemistry National Defense Medical College Tokorozawa Saitama Japan

M

Minori Dateki

Department of Biochemistry National Defense Medical College Tokorozawa Saitama Japan

T

Toru Ogata

Department of Rehabilitation for the Movement Functions Research Institute National Rehabilitation Center for Persons with Disabilities Tokorozawa Saitama Japan

R

Ryuji Uchida

Graduate School of Pharmaceutical Sciences Kitasato University Minato‐ku Tokyo Japan

H

Hiroshi Tomoda

Graduate School of Pharmaceutical Sciences Kitasato University Minato‐ku Tokyo Japan

K

Kunio Takishima

Department of Biochemistry National Defense Medical College Tokorozawa Saitama Japan

Cite This Article

Osamu Imamura, Masaaki Arai, Minori Dateki, et al. (2015). Nicotinic acetylcholine receptors mediate donepezil‐induced oligodendrocyte differentiation. Journal of Neurochemistry, 135(6), 1086-1098. https://doi.org/10.1111/jnc.13294

Nicotinic acetylcholine receptors mediate donepezil‐induced oligodendrocyte differentiation

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