Related Experiment Video
Updated: Feb 21, 2026
Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin
Published on: March 26, 2015
Unconventional Myosin ID is Involved in Remyelination After Cuprizone-Induced Demyelination
Reiji Yamazaki1, Hiroko Baba1, Yoshihide Yamaguchi2
1Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
Insights
Myosin ID (Myo1d) is crucial for central nervous system myelin repair. Knocking down Myo1d impairs myelin regeneration and promotes inflammation in a mouse model of demyelination.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Myelin, produced by oligodendrocytes (OLs) in the CNS, is vital for neuronal function.
- Myosin ID (Myo1d), an unconventional myosin, is implicated in membrane dynamics essential for myelin formation and maintenance.
- The in vivo role of Myo1d in myelin regeneration following demyelination remains largely unexplored.
Purpose of the Study:
- To investigate the in vivo function of Myosin ID (Myo1d) in the central nervous system (CNS) during myelin regeneration after demyelination.
- To elucidate the impact of Myo1d knockdown on oligodendrocyte (OL) behavior and inflammatory responses in a cuprizone-induced demyelination mouse model.
Main Methods:
- Stereotactic injection of small interfering RNA (siRNA) targeting Myo1d into the corpus callosum of cuprizone-treated mice.
- Assessment of myelin integrity using immunofluorescence staining for myelin basic protein (MBP) and myelin proteolipid protein (PLP).
- Evaluation of oligodendrocyte markers (Neural/glial antigen 2, APC/CC1), glial cell populations (microglia, astrocytes), and apoptosis (caspase 3).
Main Results:
- Myo1d knockdown in vivo reduced the expression of key myelin proteins (MBP, PLP), indicating impaired myelin regeneration.
- Oligodendrocyte numbers (APC/CC1-positive cells) and progenitor cells (NG2-positive cells) were not significantly affected by Myo1d knockdown.
- Myo1d knockdown led to an increase in pro-inflammatory microglia and astrocytes, and a decrease in anti-inflammatory microglia during the remyelination phase.
- A significant increase in caspase 3-positive cells within the oligodendrocyte population was observed following Myo1d knockdown, suggesting enhanced apoptosis.
Conclusions:
- Myosin ID (Myo1d) plays a critical role in the in vivo regeneration process following central nervous system demyelination.
- Myo1d is essential for effective myelin repair, as its absence exacerbates demyelination and hinders remyelination.
- Myo1d knockdown promotes a pro-inflammatory environment and increases oligodendrocyte apoptosis during myelin repair, highlighting its neuroprotective function.
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 cytoplasm-containing 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 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.
