Study for establishing a chemical risk evaluation method on brain development utilizing neurogenesis-related parameters

2015 Fiscal Year Final Research Report

• Project/Area Number: 25292170
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: SHIBUTANI MAKOTO 東京農工大学, (連合)農学研究科(研究院), 教授 (20311392)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Toshinori 東京農工大学, 大学院農学研究院, 准教授 (80726456) ; SUZUKI Kazuhiko 東京農工大学, 大学院農学研究院, 准教授 (00366626)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 発達神経毒性 / ニューロン新生 / 海馬歯状回 / 毒性評価法 / メチル化変動

Outline of Final Research Achievements

To construct an efficient evaluation system of developmental neurotoxicity applicable for small-scale screening, disruption mechanism and toxicity target of model compounds in the hippocampal neurogenesis were elucidated using rats. The similarity in the effect was confirmed in mice, and one interneuron gene revealing a sustained promoter region hypermethylation was identified with the compound showing irreversible effects by global genomic methylation analysis, while the compound showing reversible effects revealed one interneuron gene hypermethylated transiently. Moreover, hypermethylation of an interneuron gene identified by developmental exposure was lacked after adult-stage exposure. Conversely, a morphogenesis-related gene showing irreversible hypermethylation in mice also revealed irreversible in rats. Thus, incorporation of molecular markers for irreversibility based on genomic hypermethylation was found to be effective for evaluation of developmental neurotoxicity.

Free Research Field

農学