Kyushu University Academic Staff Educational and Research Activities Database
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Mitsuru Watanabe Last modified date:2021.12.23

Assistant Professor / Neurology
Kyushu University Hospital

 Reseacher Profiling Tool Kyushu University Pure
Academic Degree
Field of Specialization
Neurology, Neuroimmunology
Total Priod of education and research career in the foreign country
Research Interests
  • Immunology and biomarker in multiple sclerosis
    keyword : multiple sclerosis, neuromyelitis optica spectrum disorder
Academic Activities
1. Watanabe M, Nakamura Y, Sato S, Niino M, Fukaura H, Tanaka M, Ochi H, Kanda T, Takeshita Y, Yokota T, Nishida Y, Matsui M, Nagayama S, Kusunoki S, Miyamoto K, Mizuno M, Kawachi I, Saji E, Ohashi T, Shimohama S, Hisahara S, Nishiyama K, Iizuka T, Nakatsuji Y, Okuno T, Ochi K, Suzumura A, Yamamoto K, Kawano Y, Tsuji S, Hirata M, Sakate R, Kimura T, Shimizu Y, Nagaishi A, Okada K, Hayashi F, Sakoda A, Masaki K, Shinoda K, Isobe N, Matsushita T, Kira J., HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data., Scientific Reports, 10.1038/s41598-020-79833-7, 11, 1, 607-607, 2021.01.
2. Mitsuru Watanabe, Yuri Nakamura, Zuzanna Michalak, Noriko Isobe, Christian Barro, David Leppert, Takuya Matsushita, Fumie Hayashi, Ryo Yamasaki, Jens Kuhle, Jun Ichi Kira, Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD, Neurology, 10.1212/WNL.0000000000008160, 93, 13, E1299-E1311, 2019.09, ObjectiveTo test the hypothesis that serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), which are an intermediate astrocyte and neuron filaments, respectively, are clinically useful biomarkers of disease activity and disability in neuromyelitis optica spectrum disorders (NMOSD).MethodsLevels of GFAP and NfL in serum (sGFAP and sNfL, respectively) and in CSF samples were measured in healthy controls (HCs) (n = 49; 49 serum samples), patients with NMOSD (n = 33; 42 CSF and 102 serum samples), and patients with multiple sclerosis (MS) (n = 49; 53 CSF and 91 serum samples) by ultrasensitive single-molecule array assays. Association of sGFAP and sNfL levels with clinical parameters was determined.ResultsFor both GFAP and NfL, CSF and serum levels were strongly correlated. Both were higher in the serum of patients with NMOSD than in HCs (both p < 0.001). Moreover, sGFAP was higher in NMOSD than in MS (median 207.7 vs 121.1 pg/mL, p < 0.001). In NMOSD, sGFAP concentration increased after recent relapse (540.9 vs 152.9 pg/mL, p < 0.001). Multivariate analyses indicated that sGFAP and sNfL were associated with Expanded Disability Status Scale score in NMOSD (p = 0.026 and p < 0.001, respectively). Higher sGFAP/sNfL quotient at relapse differentiated NMOSD from MS with a sensitivity of 73.0% and a specificity of 75.8%.ConclusionssGFAP and sNfL are likely to be good biomarkers of disease activity and disability, and the sGFAP/sNfL quotient at relapse is a potential diagnostic marker for NMOSD..
3. Mitsuru Watanabe, Wataru Shiraishi, Ryo Yamasaki, Noriko Isobe, Motohiro Sawatsubashi, Ryuji Yasumatsu, Takashi Nakagawa, Jun-ichi Kira, Oral phase dysphagia in facial onset sensory and motor neuronopathy, Brain and Behavior, 10.1002/brb3.999, 8, 6, 2018.06, Introduction: Facial onset motor and sensory neuronopathy (FOSMN) is a rare disease whose cardinal features are initial asymmetrical facial sensory deficits followed by bulbar symptoms and spreading of sensory and motor deficits from face to scalp, neck, upper trunk, and upper extremities in a rostral–caudal direction. Although bulbar involvement is frequently observed in FOSMN, dysphagia in these patients has not been fully described. In this study, we aimed to characterize dysphagia as a prognostic factor in FOSMN by investigating our institutional case series. Methods: We retrospectively reviewed the medical records, including swallowing function tests, of six patients with FOSMN (three men and three women) who were thoroughly examined at Kyushu University Hospital between 1 January 2005 and 30 November 2017. Results: Average age at onset was 58.5 years; average disease duration was 5.7 years. All patients developed bulbar dysfunction and dysphagia (at an average of 1.8 and 2.6 years from onset, respectively), resulting in choking episodes in three patients, percutaneous endoscopic gastrostomy placement in three, and recurrent aspiration pneumonia in one. Four of five patients evaluated with videofluoroscopic swallowing studies had poor oral retention, leading to bolus flowing into the pharynx before swallowing; the fifth patient showed poor lingual transfer. Fiberoptic endoscopic evaluation of swallowing revealed leakage of blue-dyed water from the mouth to the pharynx in three patients because of poor oral retention, but only mild pharyngeal phase dysphagia in all four cases evaluated. Conclusions: Oral phase dysphagia predominates in the early stage of FOSMN..
4. Mitsuru Watanabe, Katsuhisa Masaki, Ryo Yamasaki, Jun Kawanokuchi, Hideyuki Takeuchi, Takuya Matsushita, Akio Suzumura, Jun-ichi Kira, Th1 cells downregulate connexin 43 gap junctions in astrocytes via microglial activation, Scientific Reports, 10.1038/srep38387, 6, 2016.12, We previously reported early and extensive loss of astrocytic connexin 43 (Cx43) in acute demyelinating lesions of multiple sclerosis (MS) patients. Because it is widely accepted that autoimmune T cells initiate MS lesions, we hypothesized that infiltrating T cells affect Cx43 expression in astrocytes, which contributes to MS lesion formation. Primary mixed glial cell cultures were prepared from newborn mouse brains, and microglia were isolated by anti-CD11b antibody-conjugated magnetic beads. Next, we prepared astrocyte-rich cultures and astrocyte/microglia-mixed cultures. Treatment of primary mixed glial cell cultures with interferon (IFN) γ, interleukin (IL)-4, or IL-17 showed that only IFNβ or IL-17 at high concentrations reduced Cx43 protein levels. Upon treatment of astrocyte-rich cultures and astrocyte/microglia-mixed cultures with IFNγ;, Cx43 mRNA/protein levels and the function of gap junctions were reduced only in astrocyte/microglia-mixed cultures. IFNγ-treated microglia-conditioned media and IL-1β, which was markedly increased in IFNγ-treated microglia-conditioned media, reduced Cx43 protein levels in astrocyte-rich cultures. Finally, we confirmed that Th1 cell-conditioned medium decreased Cx43 protein levels in mixed glial cell cultures. These findings suggest that Th1 cell-derived IFNγ activates microglia to release IL-1β that reduces Cx43 gap junctions in astrocytes. Thus, Th1-dominant inflammatory states disrupt astrocytic intercellular communication and may exacerbate MS..
5. Mitsuru Watanabe, Takayuki Kondo, Kenji Murakata, Takashi Kageyama, Yoko Shibata, Toshiyuki Takahashi, Kyoichi Nomura, Sadayuki Matsumoto, Antibodies to neural and non-neural autoantigens in Japanese patients with CNS demyelinating disorders, Journal of Neuroimmunology, 10.1016/j.jneuroim.2014.06.020, 274, 1-2, 155-160, 2014.01, Anti-aquaporin 4 (AQP4) antibodies (Abs) are essential in neuromyelitis optica spectrum disorders (NMOSD), but the relationship between CNS demyelinating disorders (CNSDD) and other neural Abs remains unclear. Here we screened anti-neural Abs in the sera of 70 Japanese CNSDD patients. While two had only demyelinating events among three anti. N-methyl. d-aspartate receptor (NMDAR) Ab-positive subjects, the other subject who also had anti-AQP4 Abs experienced episodes of anti-NMDAR encephalitis and of NMOSD. Major lesions in the three anti-contactin-associated protein 2 Ab-positive subjects were infratentorial, including one co-carrying anti-AQP4 Abs. Thus, autoantibodies can be clinically silent, but multiple autoantibodies may participate in the pathogenesis..
1. Mitsuru Watanabe, Noriko Isobe, Takuya Matsushita, Aleksandra Maceski, Yuri Nakamura, Katsuhisa Masaki, Jun-ichi Kira*, David Leppert*, Jens Kuhle* *These authors contributed equally to the manuscript. , Serum glial fibrillary acidic protein, but not S100B or neurofilament light chain predicts future relapses in neuromyelitis optica spectrum disorders, MSVirtual 2020 (8th Joint ACTRIMS-ECTRIMS Meeting), 2020.09.
2. Mitsuru Watanabe, Yuri Nakamura, Zuzanna Michalak, Fumie Hayashi, Christian Barro, David Leppert, Noriko Isobe, Takuya Matsushita, Ryo Yamasaki, Jens Kuhle, Jun-ichi Kira, Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD and MS, 第60回日本神経学会学術大会, 2019.05.
3. Mitsuru Watanabe, Yuri Nakamura, Zuzanna Michalak, Fumie Hayashi, Christian Barro, Noriko Isobe, Takuya Matsushita, Ryo Yamasaki, Jens Kuhle, Jun-ichi Kira, Serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in neuromyelitis optica spectrum disorders, ECTRIMS 2018, 2018.10.
4. Mitsuru Watanabe, Yuri Nakamura, Zuzanna Michalak, Fumie Hayashi, Christian Barro, Noriko Isobe, Takuya Matsushita, Ryo Yamasaki, Jens Kuhle, Jun-ichi Kira , Serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as potential biomarkers for disease activity and disability in neuromyelitis optica spectrum disorders and multiple sclerosis
, 11th PACTRIMS Congress, 2018.11.
Membership in Academic Society
  • The Japanese Society of Internal Medicine
  • Japanese Society of Neurology
  • The Japanese Society for Neuroimmunology
  • Japanese Society of Neurological Therapeutics
  • Japanese Society for Neuroinfectious Diseases
Other Educational Activities
  • 2020.09.
  • 2020.06.
  • 2020.08.
  • 2020.09.
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  • 2020.10.
  • 2020.11.
  • 2020.12.
  • 2020.07.
  • 2020.06.
  • 2018.11.
  • 2018.06.
  • 2018.09.
  • 2018.12.