Establishment of test method to detect developmental disorders in juvenile animal models by environmental factors

• Project/Area Number: 18H03036
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: University of Tsukuba
• Principal Investigator: Tohyama Chiharu 筑波大学, 医学医療系, 客員教授 (10150872)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2019: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 認知行動試験 / 幼若期マウス / 高次脳機能 / 発達神経毒性 / リスク評価 / 安全性評価 / 幼若期マウス行動試験 / 全自動行動試験 / 環境リスク評価 / 行動柔軟性 / 行動試験 / 脳発達

Outline of Final Research Achievements

Hazardous chemicals in food and the environment may disturb the infant's brain's natural growth and development. In order to detect the subtle alterations and elucidate the toxicity mechanisms, we aimed to establish behavioral tests for juvenile mice. To this end, we established the hardware and its test protocol by improving the automated cognitive behavioral assay system, IntelliCage, initially developed for adult mice. Consequently, we enabled, for the first time, to evaluate the cognitive behavior of mice 3-week-old and older. Next, we found atypical behaviors in juvenile mice born to methyl-mercury exposed dams and confirmed the applicability of the toxicity evaluation test system.

Academic Significance and Societal Importance of the Research Achievements

離乳直後の幼若期モデル動物を対象として、化学物質へのばく露に起因する行動変容を検出し、発達途上の脳や末梢組織において生じている異常状態を解明するための新たな学術的研究アプローチが可能となった。確立した認知行動試験は、全自動で実施することができるため、実験の効率性を飛躍的に高めることができる。この手法は、その新規性、効率性から、今後毒性学のみならず、神経科学や精神医学等、様々な生物医学研究分野に応用され、広く社会にその成果が還元されることが期待できる。

Research Products

• [Int'l Joint Research] University of Zurich(スイス)
• [Presentation] 幼若期マウスの全自動認知行動毒性試験法の確立 (2021)
  • Author(s): 遠藤俊裕、前川文彦、遠山千春
  • Organizer: 第48回日本毒性学会学術年会
• [Presentation] Development of an automated cognitive behavioral testing method for juvenile mice in a group-housed environment and its application to developmental neurotoxicological study (2021)
  • Author(s): Toshihiro Endo, Fumihiko Maekawa, Chiharu Tohyama
  • Organizer: EUROTOX 20212021
• [Presentation] Development of an automated neurotoxicological assay in juvenile mice (2020)
  • Author(s): Toshihiro ENDO, Seico BENNER, Hans-Peter LIPP
  • Organizer: Society of Toxicology 59 th Annual Meeting
  • Int'l Joint Research
• [Presentation] 「個性」はいつ現れるか？：離乳後からの全成長過程を追うマウス高次脳機能 試験系の確立 (2019)
  • Author(s): 遠藤 俊裕、ベナー 聖子、遠山 千春
  • Organizer: 第8回日本DOHaD学会学術集会
• [Presentation] 幼若期マウスにおける集団飼育ホームケージ環境下全自動認知行動試験法の確立 (2019)
  • Author(s): 遠藤 俊裕、ベナー 聖子、Hans-Peter LIPP、遠山 千春
  • Organizer: 第49回日本神経精神薬理学会
• [Presentation] Automated Cognitive Assay for Juvenile Mice:An application to a mixed-sex colony of C57BL/6N strain in IntelliCage (2019)
  • Author(s): Toshihiro ENDO, Seico BENNER, Hans-Peter LIPP, Chiharu TOHYAMA
  • Organizer: 第6回アジア神経精神薬理学会
  • Int'l Joint Research