Misuzu Hashimoto

Assistant Professor,Faculty of Applied Biological Sciences, Gifu University*Profile is at the time of the award.

2020Inamori Research GrantsBiology & Life sciences

Research topics
Study on the new mechanism of CNS myelin formation through identification of methylated proteins
The central nervous system consists of neuron, astrocyte, and oligodendrocyte. Oligodendrocytes form myelin sheath which enables rapid saltatory conduction of neurons. For future treatment for demyelinating diseases such as multiple sclerosis, it is important to understand the molecular mechanisms of myelin formation.
In this study, a major focus is a methyltransferase, PRMT1, which is essential for myelin development. A specific research question is ‘What is the target of methylation by PRMT1 for successful myelination?’. This study will uncover a new machinery for the proper myelin development.


Thank you very much for adoption of my research topic. I would like to contribute to the field of myelin research.

Outline of Research Achievments

Neurons in the brain perform higher-order functions through neurotransmission, and glial cells, which fill the space around neurons, are indispensable for this. I have elucidated one aspect of the mechanism of glial cell development by analyzing mice with defective glial development.

Oligodendrocytes, a type of glial cell, act as insulators and accelerate neurotransmission by producing myelin sheaths around neuronal processes. It is known that methylation modification of various intracellular proteins could alters their functions. I have previously discovered that PRMT1, a major methyltransferase, is essential for myelin formation by analyzing PRMT1-deficient mice, however, the detailed cause of this defect was unknown. In this study, we aimed to elucidate the mechanism by which PRMT1 regulates myelin formation.

Comprehensive analysis of brain gene expression and histological analysis revealed that the number of secreted factors that induce inflammation was increased in PRMT1-deficient brains prior to the peak period of myelin formation. In addition, that the number of microglia, an immune cell type, and astrocytes were increased, indicating that these cells mediated inflammatory state in the brain by loss of PRMT1. Since it has been reported that myelin is damaged in hypoxic encephalopathy and encephalitis caused by viral infection of the brain, we speculate that PRMT1 deficiency inhibit myelin formation by inducing an inflammatory state in the brain, and that would lead to neuronal function impairment.

  1. Hashimoto M, et al.  (2021) Loss of PRMT1 in the central nervous system (CNS) induces reactive astrocytes and microglia during postnatal brain development. J. Neurochem. 156: 834– 847. Epub 2020 Sep 12. https://doi.org/10.1111/jnc.15149  

  2. Hashimoto M, et al. (2021) Roles of protein arginine methyltransferase 1 (PRMT1) in brain development and disease. Biochim Biophys Acta Gen Subj. 1865(1):129776. Epub 2020 Oct 28. doi: 10.1016/j.bbagen.2020.129776

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