Intranasal exposure to ZnO nanoparticles induces alterations in cholinergic neurotransmission in rat brain

Research output: Contribution to journalArticlepeer-review

Authors

  • Yali Luo
  • Heidi Qunhui Xie
  • Swaroop Chakraborty
  • Fazel Abdolahpur Monikh
  • Lijing Bu
  • Yiyun Liu
  • Yongchao Ma
  • Zhiyong Zhang
  • Bin Zhao

External organisations

  • State Key Laboratory of Environmental Chemistry and Ecotoxicology
  • Chinese Academy of Sciences
  • Indian Institute of Technology
  • Leiden University
  • University of New Mexico
  • Institute of High Energy Physics Chinese Academy of Science

Abstract

The neurotoxicity of inhaled ZnO nanoparticles (NPs) and the underlying mechanisms remain largely unknown. In this study, ZnO NPs (30 ± 6 nm) were intranasally instilled to rats via a single dose (13 mg Zn/kg BW), with ZnSO4 as the ionic control, and analysis 7-days post exposure. The hippocampus was found to be the main target for Zn accumulation for both ZnO NPs and ZnSO4. Synchrotron radiation based X-ray absorption fine structure (XAFS) analysis showed that no particulate ZnO was found, suggesting the occurrence of dissolution and transformation of ZnO NPs. Multi-omics analysis, including transcriptomics, proteomics and metabolomics, demonstrated that cholinergic neurotransmission was the main biological process affected following both treatments. The release of the key neurotransmitter acetylcholine (ACh) was increased by enhanced ACh synthesis, upregulation of vesicular ACh transporter, and suppression of the activity of ACh hydrolysis enzyme (AChE), either by direct Zn-AChE interaction or a transcriptional down-regulation mechanism. In addition, ZnO NPs and ZnSO4 induced similar molecular consequences and exhibited the same Zn chemical speciation (100 % of Zn complexes) in the hippocampal region evidenced by XAFS analysis, suggesting that the observed biological effects were mainly derived from Zn2+ released from the ZnO NPs. This study not only evidences a new pathway for the impact of ZnO NPs on the brain, but also identifies the origin of the impact as ionic Zn, which provides the basis for safe-by-design of ZnO NPs.

Bibliographic note

Funding Information: This work was supported by the National Natural Science Foundation of China (Grant Nos. 21836004, 91543204, and 21525730), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB14030400), the National Key Research and Development Program of China (Grant No. 2018YFA0901103). Marie Sk?odowska-Curie Individual Fellowships (NanoBBB Grant Agreement No. 798505 to Z. Guo; NanoLabels Grant Agreement No. 750455 to P. Zhang) under the European Union's Horizon 2020 research program were acknowledged. Technical support from the Shanghai Applied Protein Technology facility (Shanghai, China) is gratefully acknowledged. Funding Information: This work was supported by the National Natural Science Foundation of China (Grant Nos. 21836004 , 91543204 , and 21525730 ), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB14030400 ), the National Key Research and Development Program of China (Grant No. 2018YFA0901103 ). Marie Skłodowska-Curie Individual Fellowships (NanoBBB Grant Agreement No. 798505 to Z. Guo; NanoLabels Grant Agreement No. 750455 to P. Zhang) under the European Union’s Horizon 2020 research program were acknowledged. Technical support from the Shanghai Applied Protein Technology facility (Shanghai, China) is gratefully acknowledged. Publisher Copyright: © 2020 The Author(s)

Details

Original languageEnglish
Article number100977
JournalNano Today
Volume35
Publication statusPublished - Dec 2020

Keywords

  • Acetylcholine, Acetylcholinesterase, Brain, Cholinergic neurotransmission, Zinc oxide nanoparticles