PUBLICATION

Graphene oxide quantum dots (GOQDs) induce behavioral disorders via the disturbance of kynurenine pathway in zebrafish larvae

Authors
Deng, S., Zhang, E., Zhao, Y., Guo, H., Luo, L., Yi, S., Zheng, B., Mu, X., Yuan, K., Deng, X., Rong, H., Ma, Y., Bian, W., Shen, H.
ID
ZDB-PUB-240226-4
Date
2024
Source
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP   279: 109865 (Journal)
Registered Authors
Bian, Wanping, Deng, Shun, Ma, Yanbo
Keywords
GOQDs, Kynurenine pathway, Metabolomics, Thigmotaxis, Zebrafish
MeSH Terms
  • Animals
  • Graphite*/toxicity
  • Kynurenine/pharmacology
  • Larva
  • Quantum Dots*/toxicity
  • Zebrafish
PubMed
38403007 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Abstract
The emergence of graphene quantum dots (GQDs) expands the use of graphene derivatives in nanomedicine for its direct therapeutic applications in treating neurodegeneration, inflammation, metabolic dysfunction, and among others. Nevertheless, the biosafety assessment of GQDs remains deficient mostly because of the diverse surface characteristics of the nanoparticles. Our prior work demonstrated that GQDs can induce strong thigmotactic effects in zebrafish larvae over a wide range of concentrations, yet the underlying metabolic mechanisms remain largely unknown. In this study, we conducted a further exploration about graphene oxide quantum dots (GOQDs) for its potential neurotoxic effect on the behaviors of zebrafish larvae by combining neurotransmitter-targeted metabolomics with locomotion analysis. After continuous exposure to a concentration gradient of GOQDs (12.5 - 25 - 50 - 100 - 200 μg/mL) for 7 days, the thigmotactic activities of zebrafish larvae were observed across all exposure concentrations relative to the control group, while the basal locomotor activities, including distance moved and average velocity, were significantly changed by low concentrations of GOQDs. Targeted metabolomics was performed using zebrafish larvae at 7 days post-fertilization (dpf) that were exposed to 12.5 and 200 μg/mL, both of which were found to perturb the kynurenine pathway by regulating the levels of kynurenine, 3-hydroxyanthranilic acid (3-HAA), and quinolinic acid (QA). Furthermore, the thigmotaxis of larval fish induced by GOQDs during exposure could be counteracted by supplementing Ro-61-8048, an agonist acting on kynurenine 3-monooxygenase (KMO). In conclusion, our study establishes the involvement of the kynurenine pathway in GOQDs-induced thigmotaxis, which is independent of the transcriptional modulation of glutamate receptor families.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping