connexin cytopathy in the pathogenesis of demyelinating disorders

• Project/Area Number: 25293204
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyushu University
• Principal Investigator: Kira Jun-ichi 九州大学, 医学(系)研究科(研究院), 教授 (40183305)
• Co-Investigator(Kenkyū-buntansha): Matsushita Takuya 九州大学, 大学院医学研究院, 講師 (00533001) ; Yamasaki Ryo 九州大学病院, 講師 (10467946) ; Masaki Katsuhisa 九州大学, 大学院医学研究院, 助教 (90612903)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 多発性硬化症 / 視神経脊髄炎 / Balo病 / コネキシン / アストロサイト / アクアポリン4 / グリアアセンブリ / グリアシンシチウム / オリゴデンドロサイト / エネルギー供給障害 / 脱髄性疾患 / グリア細胞

Outline of Final Research Achievements

We found the extensive loss of connexins in active lesions of demyelinating disorders including multiple sclerosis, neuromyelitis optica and Balo's disease.Also we performed combined neuropathological and neuroradiological studies in spinal cord lesions from NMO patients. We showed all of isolated perivascular lesions, early lesion of NMO, were located in lateral and posterior columns in spinal cord. In addition, we examined whether T lymphocyte could influence cultured astrocytic Cx43 by using in vitro assay. We revealed that Th1-derived factor could downregulate the expression of astrocytic Cx43.

Research Products

• [Journal Article] Efficacy of intravenous methylprednisolone pulse therapy in patients with multiple sclerosis and neuromyelitis optica (2016)
  • Author(s): Yamasaki R, Matsushita T, Fukazawa T, Yokoyama K, Fujihara K, Ogino M, Yokota T, Miyamoto K, Niino M, Nomura K, Tomioka R, Tanaka M, Kawachi I, Ohashi T, Kaida KI, Matsui M, Nakatsuji Y, Ochi H, Fukaura H, Kanda T, Nagaishi A, Togo K, Mizusawa H, Murai H, Kira JI
  • Journal Title: Multiple sclerosis Volume: 印刷中 Issue: 10 Pages: 1337-1348
  • DOI: 10.1177/1352458515617248
  • Peer Reviewed
• [Journal Article] Characterization of IgG4 anti-neurofascin 155 antibody-positive polyneuropathy. (2015)
  • Author(s): Ogata H, et al
  • Journal Title: Ann Clin Transl Neurol. Volume: 2 Issue: 10 Pages: 960-971
  • DOI: 10.1002/acn3.248
  • Peer Reviewed
• [Journal Article] Neuromagnetic evidence for hippocampal modulation of auditory processing. (2015)
  • Author(s): Chatani H, et al
  • Journal Title: Neuroimage Volume: 124 Pages: 256-266
  • Peer Reviewed
• [Journal Article] Japan Multiple Sclerosis Genetics Consortium Copy Number Variations in Multiple Sclerosis and Neuromyelitis Optica. (2015)
  • Author(s): S. Sato, K. Yamamoto, T. Matsushita, N. Isobe, Y. Kawano, K, Iinuma, M. Niino, T. Fukazawa, Y. Nakamura, M. Watanabe, T. Yonekawa, K. Masaki, S. Yoshimura, H. Murai, R. Yamasaki, J. Kira
  • Journal Title: Annals of Neurology Volume: 78 Issue: 5 Pages: 762-774
  • DOI: 10.1002/ana.24511
  • Peer Reviewed
• [Journal Article] Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod (2015)
  • Author(s): Song ZY, Yamasaki R, Kawano Y, Sato S, Masaki K, Yoshimura S, Matsuse D, Murai H,Matsushita T, Kira J
  • Journal Title: PLoS One Volume: 10 Issue: 4 Pages: e0124923-e0124923
  • DOI: 10.1371/journal.pone.0124923
  • Peer Reviewed / Open Access
• [Journal Article] A nationwide survey of combined central and peripheral demyelination in Japan. (2015)
  • Author(s): Hidenori Ogata
  • Journal Title: Journal of Neurology, Neurosurgery & Psychiatry Volume: 未定 Pages: 29-36
  • DOI: 10.1136/jnnp-2014-309831
  • Peer Reviewed
• [Journal Article] Decreased serum vitamin D levels in Japanese patients with multiple sclerosis. (2015)
  • Author(s): Niino M, et al
  • Journal Title: J Neuroimmunol Volume: 279 Pages: 40-45
  • Peer Reviewed
• [Journal Article] Latitude and HLA-DRB1 alleles independently affect the emergence of cerebrospinal fluid IgG abnormality in multiple sclerosis. (2015)
  • Author(s): Niino M, et al
  • Journal Title: Mult Scler Volume: 21 Issue: 9 Pages: 1112-1120
  • DOI: 10.1177/1352458514560924
  • Peer Reviewed
• [Journal Article] Early and Extensive Spinal White Matter Involvement in Neuromyelitis Optica. (2015)
  • Author(s): Hayashida S, et al
  • Journal Title: Brain Pathol Volume: in press Issue: 3 Pages: 249-265
  • DOI: 10.1111/bpa.12386
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] South Japan Multiple Sclerosis Genetics Consortium. Interleukin 2 receptor α chain gene polymorphisms and risks of multiple sclerosis and neuromyelitis optica in southern Japanese (2014)
  • Author(s): Ainiding G, Kawano Y, Sato S, Isobe N, Matsushita T, Yoshimura S, Yonekawa T, Yamasaki R, Murai H, Kira J
  • Journal Title: J Neurol Sci. Volume: 337(1-2) Issue: 1-2 Pages: 147-50
  • DOI: 10.1016/j.jns.2013.11.037
  • Peer Reviewed
• [Journal Article] Fingolimod (FTY720) therapy in Japanese patients with relapsing multiple sclerosis over 12-months: results of a phase 2 observational extension. (2014)
  • Author(s): Kira J, et al.
  • Journal Title: BMC Neurol Volume: 14 Issue: 1 Pages: 21-21
  • DOI: 10.1186/1471-2377-14-21
  • Peer Reviewed
• [Journal Article] Galectin-1 deficiency improves axonal swelling of motor neurons in SOD1 transgenic mice. (2014)
  • Author(s): Kobayakawa, Y., Sakumi, K., Kajitani, K., Kadoya, T., Horie, H., Kira, J.I., and Nakabeppu, Y.
  • Journal Title: Neuropathol Appl Neurobiol Volume: N/A Issue: 2 Pages: 227-244
  • DOI: 10.1111/nan.12123
  • Peer Reviewed
• [Journal Article] Extensive dysregulations of oligodendrocytic and astrocytic connexins are associated with disease progression in an amyotrophic lateral sclerosis mouse model. (2014)
  • Author(s): Cui Y and Masaki K et al
  • Journal Title: J Neuroinflammation Volume: 11 Issue: 1 Pages: 42-42
  • DOI: 10.1186/1742-2094-11-42
  • Peer Reviewed / Open Access
• [Journal Article] Decreased CCR2 and CD62L expressions on peripheral blood classical monocytes in amyotrophic lateral sclerosis. (2014)
  • Author(s): Cui Y, et al.
  • Journal Title: Clin Exp Neuroimmunol Volume: 5 Issue: 1 Pages: 92-96
  • DOI: 10.1111/cen3.12088
  • Peer Reviewed / Open Access
• [Journal Article] Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients. (2014)
  • Author(s): Yoshimura S, Isobe N, Matsushita T, Masaki K, Sato S, Kawano Y, Ochi H, Kira J.
  • Journal Title: PLoS One Volume: 9(4) Issue: 4 Pages: e95367-e95367
  • DOI: 10.1371/journal.pone.0095367
  • Peer Reviewed / Open Access
• [Journal Article] Distinct cytokine and T helper cell profiles between patients with multiple sclerosis who had or had not received interferon-beta. (2014)
  • Author(s): Doi H, et al.
  • Journal Title: Clin Exp Neuroimmunol Volume: 5 Issue: 3 Pages: 321-327
  • DOI: 10.1111/cen3.12138
  • Peer Reviewed / Open Access
• [Journal Article] A nationwide survey of hypertrophic pachymeningitis in Japan (2013)
  • Author(s): Yonekawa T, Murai H, Utsuki S, Matsushita T, Masaki K, Isobe N, Yamasaki R, Yoshida M, Kusunoki S, Sakata K, Fujii K, Kira J
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 85 Issue: 7 Pages: 732-9
  • DOI: 10.1136/jnnp-2013-306410
  • Peer Reviewed
• [Presentation] Common and Distinct Features of Immunopathology Between MS and NMO (2015)
  • Author(s): Masaki K
  • Organizer: PACTRIMS 2015
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2015-11-19
  • Int'l Joint Research / Invited
• [Presentation] Extensive Loss of Astrocytic Monocarboxylate Transporter 4 in Active Lesions of Multiple Sclerosis and Neuromyelitis Optica (2015)
  • Author(s): Masaki K, et al
  • Organizer: ECTRIMS 2015
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2015-10-07
  • Int'l Joint Research
• [Presentation] Autoimmunity targeting axo-glial interface (2015)
  • Author(s): Kira J
  • Organizer: APSNI 2015
  • Place of Presentation: Tokyo
  • Year and Date: 2015-08-30
  • Int'l Joint Research / Invited
• [Presentation] A combined neuroimaging and neuropathological study for longitudinally extensive spinal cord lesions in neuromyelitis optica (2015)
  • Author(s): Hayashida et al
  • Organizer: AAN 2015
  • Place of Presentation: Washington
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Neuropathological study of glucose and monocarboxylate transporters in multiple sclerosis. (2014)
  • Author(s): 眞﨑勝久
  • Organizer: ECTRIMS 2014
  • Place of Presentation: Boston
  • Year and Date: 2014-09-12
• [Presentation] MSにおけるastrocytopathy (2014)
  • Author(s): 眞﨑勝久
  • Organizer: 第26回日本神経免疫学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2014-09-06
  • Invited
• [Presentation] 脱髄性疾患における広汎なコネキシン脱落と病態への関与 (2014)
  • Author(s): 眞﨑勝久
  • Organizer: 第55回日本神経病理学会総会学術研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-06-06
  • Invited
• [Presentation] 脱髄性疾患における広汎なConnexin 43脱落は病態の急速な進行およびdistal oligodendrogliopathy型脱髄と関連する (2014)
  • Author(s): 眞﨑勝久
  • Organizer: 第55回日本神経病理学会総会学術研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-06-06
• [Presentation] 脱髄性疾患におけるグルコース・乳酸トランスポーター発現の神経病理学的検討 (2014)
  • Author(s): 眞﨑勝久
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-23
• [Presentation] Th1細胞によるアストロサイトのコネキシン発現抑制作用 (2014)
  • Author(s): 渡邉充
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-23
• [Presentation] 神経科学と免疫科学の統合による神経難病のパラダイムシフトをめざして (2014)
  • Author(s): 吉良潤一
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-22
  • Invited
• [Presentation] Connexin Gap Junction Pathology in active MS, Baló’s disease and NMO. (2014)
  • Author(s): 眞﨑勝久
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-21
  • Invited
• [Book] 免疫性神経疾患 病態と治療のすべて (2015)
  • Author(s): 吉良潤一
  • Total Pages: 551
  • Publisher: 中山書店
• [Book] 免疫性神経疾患 病態と治療のすべて (2015)
  • Author(s): 真崎勝久
  • Total Pages: 551
  • Publisher: 中山書店
• [Book] 免疫性神経疾患 基礎・臨床研究の最新知見 (2015)
  • Author(s): 吉良潤一
  • Total Pages: 883
  • Publisher: 日本臨床社
• [Book] 免疫性神経疾患 基礎・臨床研究の最新知見 (2015)
  • Author(s): 真崎勝久
  • Total Pages: 883
  • Publisher: 日本臨床社
• [Book] 免疫症候群(第2版)Ⅰ (2015)
  • Author(s): 真崎勝久
  • Total Pages: 931
  • Publisher: 日本臨床社