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

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dc.contributor.author Chakraborty, Swaroop et al.
dc.date.accessioned 2020-10-06T07:55:36Z
dc.date.available 2020-10-06T07:55:36Z
dc.date.issued 2020-12
dc.identifier.citation Chakraborty, Swaroop et al., "Intranasal exposure to ZnO nanoparticles induces alterations in cholinergic neurotransmission in rat brain", Nano Today, DOI: 10.1016/j.nantod.2020.100977, vol. 35, Dec. 2020. en_US
dc.identifier.issn 1748-0132
dc.identifier.uri https://doi.org/10.1016/j.nantod.2020.100977
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/5731
dc.description.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.
dc.description.statementofresponsibility by Swaroop Chakraborty et al.
dc.language.iso en_US en_US
dc.publisher Elsevier en_US
dc.subject Zinc oxide nanoparticles en_US
dc.subject Brain en_US
dc.subject Cholinergic neurotransmission en_US
dc.subject Acetylcholine en_US
dc.subject Acetylcholinesterase en_US
dc.title Intranasal exposure to ZnO nanoparticles induces alterations in cholinergic neurotransmission in rat brain en_US
dc.type Article en_US
dc.relation.journal Nano Today


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