Unconventional Myosin ID is Involved in Remyelination After Cuprizone-Induced Demyelination
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ORIGINAL PAPER
Unconventional Myosin ID is Involved in Remyelination After Cuprizone-Induced Demyelination Reiji Yamazaki1 · Hiroko Baba1 · Yoshihide Yamaguchi1
Received: 20 July 2017 / Revised: 25 September 2017 / Accepted: 4 October 2017 © Springer Science+Business Media, LLC 2017
Abstract Myelin, which is a multilamellar structure that sheathes the axon, is essential for normal neuronal function. In the central nervous system (CNS), myelin is produced by oligodendrocytes (OLs), which wrap their plasma membrane around axons. The dynamic membrane trafficking system, which relies on motor proteins, is required for myelin formation and maintenance. Previously, we reported that myosin ID (Myo1d) is distributed in rat CNS myelin and is especially enriched in the outer and inner cytoplasmcontaining loops. Further, small interfering RNA (siRNA) treatment highlighted the involvement of Myo1d in the formation and maintenance of myelin in cultured OLs. Myo1d is one of the unconventional myosins, which may contribute to membrane dynamics, either in the wrapping process or transport of myelin membrane proteins during myelination. However, the function of Myo1d in myelin formation in vivo remains unclear. In the current study, to clarify the function of Myo1d in vivo, we surgically injected siRNA in the corpus callosum of a cuprizone-treated demyelination mouse model via stereotaxy. Knockdown of Myo1d expression in vivo decreased the intensities of myelin basic protein and myelin proteolipid protein immunofluorescence staining. However, neural/glial antigen 2-positive signals and adenomatous polyposis coli (APC/CC1)-positive cell numbers were unchanged by siRNA treatment. Furthermore, Myo1d knockdown treatment increased pro-inflammatory microglia and astrocytes during remyelination. In contrast, anti-inflammatory microglia were decreased. The percentage * Yoshihide Yamaguchi [email protected] 1
Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Sciences, 1432‑1 Horinouchi, Hachioji, Tokyo 192‑0392, Japan
of caspase 3-positive cells in total CC1-positive OLs were also increased by Myo1d knockdown. These results indicated that Myo1d plays an important role during the regeneration process after demyelination. Keywords Myelin · Oligodendrocyte · Cytoskeleton · Cuprizone · In vivo siRNA · Remyelination
Introduction Myelin is a unique multi-layered membrane structure that sheathes the axon, and is essential for normal neuronal function. In the central nervous system (CNS), oligodendrocytes (OLs) produce myelin membrane by wrapping their processes around axons [1, 2]. Multiple sclerosis (MS) is an immune-mediated demyelinating disease in the CNS. Since the molecular mechanisms of how OLs form myelin during myelination and remyelination has not been completely elucidated, there is currently no available therapy to promote remyelination in MS. Each OL extends many processes producing multiple myelin sheaths. Therefore, a dynamic membrane trafficking system, which relies on cytoskeletal proteins
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