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使用双光子显微镜体内成像技术阐明在未观察到有害作用水平(NOAEL)下暴露于噻虫胺的神经学效应。

Elucidation of the neurological effects of clothianidin exposure at the no-observed-adverse-effect level (NOAEL) using two-photon microscopy in vivo imaging.

作者信息

Nishi Misaki, Sugio Shouta, Hirano Tetsushi, Kato Daisuke, Wake Hiroaki, Shoda Asuka, Murata Midori, Ikenaka Yoshinori, Tabuchi Yoshiaki, Mantani Youhei, Yokoyama Toshifumi, Hoshi Nobuhiko

机构信息

Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Hyogo, Japan.

Department of Anatomy and Molecular Cell Biology, Graduate School of Medicine, Nagoya University, Aichi, Japan.

出版信息

J Vet Med Sci. 2022 Apr 15;84(4):585-592. doi: 10.1292/jvms.22-0013. Epub 2022 Mar 10.

Abstract

Neonicotinoid pesticides (NNs) cause behavioral abnormalities in mammals, raising concerns about their effects on neural circuit activity. We herein examined the neurological effects of the NN clothianidin (CLO) by in vivo Ca imaging using two-photon microscopy. Mice were fed the no-observed-adverse-effect-level (NOAEL) dose of CLO for 2 weeks and their neuronal activity in the primary somatosensory cortex (S1) was observed weekly for 2 weeks. CLO exposure caused a sustained influx of Ca in neurons in the S1 2/3 layers, indicating hyperactivation of neurons. In addition, microarray gene expression analysis suggested the induction of neuroinflammation and changes in synaptic activity. These results demonstrate that exposure to the NOAEL dose of CLO can overactivate neurons and disrupt neuronal homeostasis.

摘要

新烟碱类杀虫剂(NNs)会导致哺乳动物出现行为异常,这引发了人们对其对神经回路活动影响的担忧。我们在此通过使用双光子显微镜进行体内钙成像,研究了NN噻虫胺(CLO)的神经学效应。给小鼠喂食无可见不良作用水平(NOAEL)剂量的CLO,持续2周,并在2周内每周观察其初级体感皮层(S1)中的神经元活动。接触CLO导致S1 2/3层神经元中持续的钙内流,表明神经元过度激活。此外,微阵列基因表达分析表明存在神经炎症的诱导和突触活动的变化。这些结果表明,接触NOAEL剂量的CLO会使神经元过度激活并破坏神经元的稳态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db92/9096047/1d4ab3d0bad3/jvms-84-585-g001.jpg

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