Developmental stage-specific exposure and neurotoxicity evaluation of low-dose clothianidin during neuronal circuit formation

Asuka Shoda, Midori Murata, Mako Kimura, Yukako Hara, Sakura Yonoichi, Yuya Ishida, Youhei Mantani, Toshifumi Yokoyama, Tetsushi Hirano, Yoshinori Ikenaka, Yoshiaki Tabuchi, Nobuhiko Hoshi*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

5 被引用数 (Scopus)

抄録

Neonicotinoid pesticides (NN) were recently reported to exhibit adverse effects in higher vertebrates. Moreover, NNs are routinely transferred from mother to offspring, raising concerns about their effects on future generations. The fetal and neonatal periods are the most critical to the formation of neural circuits in the brain through neurogenesis and differentiation, neuronal migration, axon guidance, and synaptogenesis. NN exposure throughout the fetal and neonatal periods was found to affect the neurobehavior of the offspring, but the stage-specific neurobehavioral effects are unclear. We exposed fetal and neonatal mice to a no-observed-adverse-effect level (NOAEL) of clothianidin (CLO) for 4 days during each of four developmental stages: neurite proliferation and differentiation (fetal days 9–12, CLO-1), neurite outgrowth (fetal days 15–18, CLO-2), synapse formation and astrocyte differentiation (days 1–4 after birth, CLO-3), and synapse remodeling (days 11–14 after birth, CLO-4). CLO’s neurobehavioral effects were evaluated in juveniles and adults, revealing that CLO-1 and CLO-2 caused behavioral abnormalities in adult mice. CLO-3 significantly increased locomotor activity and decreased juvenile neurons in the hippocampal dentate gyrus in adulthood. Comprehensive gene analysis of CLO-3 revealed high expression of genes related to neurite outgrowth and axonal branching in the hippocampus in juveniles and adults. These results revealed developmental stage-specific effects of a NOAEL of CLO in the fetal and neonatal periods, suggesting that the susceptibility of the fetus and neonate to CLO varies by developmental stage.

本文言語英語
ページ(範囲)486-496
ページ数11
ジャーナルJournal of Veterinary Medical Science
85
4
DOI
出版ステータス出版済み - 2023

ASJC Scopus 主題領域

  • 獣医学一般

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