Evaluation of glial cells in developmental neurotoxicity using neural differentiation tracer mice

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K21332
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 1101:Environmental analyses and evaluation, environmental conservation measure and related fields
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: Ishida Keishi 岐阜薬科大学, 薬学部, 助教 (90908310)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: in vivoイメージング / レポータートランスジェニックマウス / 発達神経毒性 / グリア細胞

Outline of Final Research Achievements

In the current study, we investigated the relationship between chemicals-induced developmental neurotoxicity (DNT) and glial cells using reporter transgenic mice (Syn-Rep mice), which we have originally generated. The reporter gene expression was changed in the brain of Syn-Rep mice pups, which was prenatally treated with valproate, a DNT reference chemical. This result suggests that the Syn-Rep mice are potentially useful tools for detection of chemical-induced DNT. In the maternal immune activation model, the changes in the reporter gene expression and morphologies of the glial activation were detected in the brain of Syn-Rep mice pups. These results suggest that the Syn-Rep mice can detect the effects of chemicals on neuronal development via glial cells.

Free Research Field

発達神経毒性学

Academic Significance and Societal Importance of the Research Achievements

近年、グリア細胞に特化したin vitro DNT試験法の開発が国際的に求められているが、グリア細胞とDNTの関係に不明な点が多いため現状その開発はほとんど進んでいない。Syn-Repマウスを用いてDNTとグリア細胞の関係を効率的に検討することで、グリア細胞特有のDNTマーカーの同定が可能になるとともに、グリア細胞をベースにしたin vitro DNT試験系の構築に多大な貢献ができると期待される。