Elucidation of expression mechanism of acrylamide-induce neurotoxicity, and development of therapeutic effects by vitamin B1.

• Project/Area Number: 17H07105
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Hygiene and public health
• Research Institution: Showa University
• Principal Investigator: Nagashima Daichi 昭和大学, 医学部, 助教 (20713720)
• Research Collaborator: Yamano Yuko ; Ichihara Gaku ; Ichihara Sahoko ; Sakurai Toshihiro
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: アクリルアミド / 神経毒性 / プロテオーム解析 / プロテオミクス

Outline of Final Research Achievements

In this study, we attempted to elucidate the mechanism of acrylamide-induced neurotoxicity and to search for a therapeutic effect for neurotoxicity by vitamin B1. The expression of five proteins confirmed by Western blotting was performed in PC12 cells. PC12 cells were elongated by nerve growth factor and acrylamide was exposed at concentrations from 0mM to 10mM. As a result of this study, there were no significant changes in the expression of five proteins, unlike the animal experiments. However, concentration of intracellular ATP was significantly reduced at 30 minutes after exposure. We administered vitamin B1 after exposure to acrylamide, there was no significant recovery thorough the amount of ATP.

Academic Significance and Societal Importance of the Research Achievements

acrylamideは疫学研究において、長期曝露により感覚障害や歩行障害といいた末梢神経のみならず、記憶障害や言語障害、抑うつ症状といった中枢神経障害を引き起こすことが知られているが、その毒性発現メカニズムは十分に解明されていない。本研究結果では、acrylamide曝露時の影響マーカーを探索し、エネルギー産生量について検討することで、神経毒性発現メカニズムの一端を明らかにした。

Research Products

• [Journal Article] Proteomic analysis of hippocampal proteins in acrylamide-exposed Wistar rats (2019)
  • Author(s): Daichi Nagashima、Lingyi Zhang、Yuki Kitamura、Sahoko Ichihara、Eri Watanabe、Cai Zong、Yuko Yamano、Toshihiro Sakurai、Shinji Oikawa、Gaku Ichihara
  • Journal Title: Archives of Toxicology Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of microglial activation and neuroinflammation in neurotoxicity of acrylamide in vivo and in vitro (2019)
  • Author(s): Zong Cai, Hasegawa Rieka, Urushitani Makoto, Zhang Lingyi, Nagashima Daichi, Sakurai Toshihiro, Ichihara Sahoko, Ohsako Seiichiro, Ichihara Gaku
  • Journal Title: Archives of Toxicology Volume: 印刷中 Issue: 7 Pages: 2007-2019
  • DOI: 10.1007/s00204-019-02471-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Proteomic Analysis of Liver Proteins of Mice Exposed to 1,2-dichloropropane (2019)
  • Author(s): X. Zhang, K. Morikawa, Y. Mori, C. Zong, L. Zhang, E. Garner, C. Huang, W. Wu, J. Chang, D. Nagashima, T. Sakurai, S. Ichihara, S. Oikawa and G. Ichihara
  • Organizer: Society of Toxicology 58th Annual Meeting
  • Int'l Joint Research
• [Presentation] 1,2-ジクロロプロパン曝露マウスにおける肝臓のプロテオミクス (2018)
  • Author(s): 森川浩太, 張驍, 森有利絵, 宗才, 張霊逸、エドウィン ガーナ―、黄晉彦、呉文亭、常杰、長嶋大地、櫻井敏博、市原佐保子、及川伸二、市原学
  • Organizer: 第13回ナノ・バイオメディカル学会
• [Presentation] Autophagy in the cerebellar Purkinje cell induced by exposure to acrylamide (2017)
  • Author(s): M. Yamamura, K. Morita, T. Matsuzoe, L. Zhang, K. Morita, C. Zhong, D. Nagashima, T. Sakurai, S. Ichihara, G. Ichihara
  • Organizer: 10th International Symposium on Biological Monitoring in Occupational and Environmental Health
  • Int'l Joint Research