Molecular mechanism underling inflammatory hypothesis of cerebellum damage caused by methylmercury

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790134
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Environmental pharmacy
• Research Institution: Tokyo University of Science (2010); Hokuriku University (2009)
• Principal Investigator: HIROOKA Takashi Tokyo University of Science, 薬学部, 助教 (50397519)
• Project Period (FY): 2009 – 2010
• Keywords: メチル水銀 / 小脳障害 / 炎症仮説 / 脳微小血管内皮細胞 / 脳微小血管周皮細胞 / ヒアルロナン / Aldose reductase

Research Abstract

We hypothesize that selective damage of methylmercury to granular cell layer in cerebellum might be due to the inflammation of tissue caused by methylmercury. In present study, we found that methylmercury stimulates the synthesis of hyaluronan and expression of aldose reductase in cultured human brain microvascular cells. Hyaluronan and aldose reductase are involved in development of inflammatory lesion. These results suggest the possibility that regulation of expression of hyaluronan and aldose reductase might be one of the molecular mechanism underling inflammation of cerebellar tissue caused by methylmercury.

Research Products

• [Journal Article] Resistance of human brain microvascular endothelial cells in culture to methylmercury: cell-density-dependent defense mechanisms. (2010)
  • Author(s): Takashi Hirooka, Yasuyuki Fujiwara, Yasuhiro Shinkai, Chika Yamamoto, Akira Yasutake, Masahiko Sato, Komyo Eto, Toshiyuki Kaji.
  • Journal Title: The Journal of Toxicological Sciences. 35 Pages: 287-294
  • Peer Reviewed
• [Journal Article] Cell-density-dependent methylmercury susceptibility of cultured human brain microvascular pericytes. (2010)
  • Author(s): Takashi Hirooka, Yasuyuki Fujiwara, Yuka Minami, Akihiko Ishii, Mio Ishigooka, Yasuhiro Shinkai, Chika Yamamoto, Akira Yasutake, Masahiko Sato, Komyo Eto, Toshiyuki Kaji.
  • Journal Title: Toxicology in Vitro. 24 Pages: 835-841
  • Peer Reviewed
• [Presentation] 傷害ヒト脳微小血管内皮細胞層の修復に対するメチル水銀の阻害作用は低酸素下において増強される (2011)
  • Author(s): 廣岡孝志
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-30
• [Presentation] The microvascular cells are a target of methylmercury toxicity, NIMD FORUM 2011 Methylmercury toxicology: Up-to-date Research on Mechanisms. (2011)
  • Author(s): 廣岡孝志
  • Organizer: Toxicology and Pathology.
  • Place of Presentation: 水俣市
  • Year and Date: 2011-01-27
• [Presentation] ヒト脳微小血管内皮細胞層に対するメチル水銀の毒性発現は低酸素環境下において増強される (2010)
  • Author(s): 廣岡孝志
  • Organizer: フォーラム2010衛生薬学・環境トキシコロジー
  • Place of Presentation: 東京
  • Year and Date: 2010-09-10
• [Presentation] メチル水銀の血管毒性に関する研究 (2010)
  • Author(s): 廣岡孝志
  • Organizer: フォーラム2010衛生薬学・環境トキシコロジー(平成22年度日本薬学会環境.衛生部会賞受賞講演)
  • Place of Presentation: 東京
  • Year and Date: 2010-09-10
• [Presentation] メチル水銀はヒト脳微小血管内皮および周皮細胞のヒアルロナン合成を誘導する (2010)
  • Author(s): 廣岡孝志
  • Organizer: 第37回日本トキシコロジー学会学術年会
  • Place of Presentation: 沖縄
  • Year and Date: 2010-06-18
• [Presentation] メチル水銀は脳浮腫形成に関与する脳血管組織のVEGFシステムを活性化する (2010)
  • Author(s): 廣岡孝志
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-30
• [Presentation] メチル水銀は培養ヒト脳微小血管内皮細胞および周皮細胞のヒアルロナン合成を促進する (2009)
  • Author(s): 廣岡孝志
  • Organizer: フォーラム2009衛生薬学・環境トキシコロジー
  • Place of Presentation: 沖縄
  • Year and Date: 2009-11-06
• [Presentation] メチル水銀による小脳障害のメカニズムに関する新しい仮説 (2009)
  • Author(s): 廣岡孝志
  • Organizer: 第36回日本トキシコロジー学会学術年会(優秀研究発表賞受賞)
  • Place of Presentation: 岩手県
  • Year and Date: 2009-07-07
• [Remarks] ホームページ等