2021 Fiscal Year Final Research Report

Developing evaluation methods for the effects of ionic environmental pollutants on neurotransmitters

Research Project

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Project/Area Number	19K22933
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 64:Environmental conservation measure and related fields
Research Institution	Ehime University
Principal Investigator	Nomiyama Kei 愛媛大学, 沿岸環境科学研究センター, 准教授 (30512686)
Co-Investigator(Kenkyū-buntansha)	水川葉月愛媛大学, 農学研究科, 准教授 (60612661) 池中良徳北海道大学, 獣医学研究院, 教授 (40543509)
Project Period (FY)	2019-06-28 – 2022-03-31
Keywords	イオン性環境汚染物質 / 脳移行 / 質量イメージング / 神経伝達物質 / ネオニコチノイド
Outline of Final Research Achievements	Monoamine neurotransmitters (MAs), including dopamine (DA) and serotonin (5-HT), regulate brain functions such as behavior, memory, and learning. Neonicotinoids are pesticides that are being used more frequently. Neonicotinoid exposure has been observed to produce neurological symptoms, such as altered spontaneous movements and anxiety-like behaviors, which are suspected to be caused by altered MA levels. In this study, we developed a sensitive and accurate analytical method using liquid chromatography-mass spectrometry (LC-MS/MS) to clarify the effects of neonicotinoid administration on MAs in the brain. We orally administered the neonicotinoid imidacloprid to mice. The LC-MS/MS quantification of MAs in various brain regions by DPP derivatization, which was newly developed in this study, showed a decrease in some MA levels in the olfactory bulb and the striatum. Thus, in this study, we developed a new method for the sensitive detection of MAs by LC/MS using DPP derivatization.
Free Research Field	環境分析化学・環境毒性学
Academic Significance and Societal Importance of the Research Achievements	脳神経作用への作用機序の解明にはこれら脳内関連物質を含めた包括的な分析が必要であるが、高マトリクスな脳試料を対象とした分析は容易ではなく、神経伝達物質の包括的分析法は達成されていない。本研究で新たに開発したDPP誘導体化によるMSIおよびLC/MS定量法により、NNが脳の各部位においてモノアミン濃度を変化させ、さらに低濃度によっても変化させることをグラフィカルに初めて明らかにすることが出来た。本研究成果は、曝露実験で得られた結果と併せて化学物質の脳移行による異常行動を予測する技術にも応用できると考えており、当該研究分野の発展に繋がる斬新かつチャレンジ性のあるアイディアの創生が期待される。