PUBLICATION
Development and Molecular Investigation into the Effects of Carbamazepine Exposure in the Zebrafish (Danio rerio)
- Authors
- Chen, H., Yang, H., Zhao, Y., Gu, X., Martyniuk, C.J.
- ID
- ZDB-PUB-201203-1
- Date
- 2020
- Source
- International Journal of Environmental Research and Public Health 17(23): (Journal)
- Registered Authors
- Keywords
- Danio rerio, carbamazepine, gamma-aminobutyric acid, glutamate, pharmaceuticals
- MeSH Terms
-
- Animals
- Carbamazepine*/toxicity
- Embryo, Nonmammalian
- Embryonic Development
- Humans
- Larva
- Nerve Tissue Proteins
- Receptors, N-Methyl-D-Aspartate
- Water Pollutants, Chemical*/toxicity
- Zebrafish
- Zebrafish Proteins
- PubMed
- 33260372 Full text @ Int. J. Environ. Res. Public Health
Citation
Chen, H., Yang, H., Zhao, Y., Gu, X., Martyniuk, C.J. (2020) Development and Molecular Investigation into the Effects of Carbamazepine Exposure in the Zebrafish (Danio rerio). International Journal of Environmental Research and Public Health. 17(23):.
Abstract
Concerns regarding environmental exposures and the impacts of pharmaceuticals on non-target aquatic organisms continue to increase. The antiepileptic drug carbamazepine (CBZ) is often detected as an aquatic contaminant and can disrupt various behaviors of fishes. However, there are few reports which investigate the mechanism of CBZ action in fish. The aim of the current study was to evaluate the effects of CBZ on embryonic development (i.e., hatching rate, heart rate, and body length) and early spontaneous movement. Moreover, we sought to investigate potential mechanisms by focusing on the gamma-aminobutyric acid (GABA) neurotransmitter system in zebrafish 6 days after of exposure. The results show that CBZ exposure did not cause significant effects on embryo development (hatching rate, heart rate, nor body length) at the test concentrations. However, the early spontaneous movement of embryos was inhibited following 10 μg/L CBZ exposure at 28-29 h post-fertilization (hpf). In addition, acetylcholinesterase (AChE) activity and GABA concentrations were increased with exposure, whereas glutamate (Glu) concentrations were decreased in larval zebrafish. Gene expression analysis revealed that GABA and glutamate metabolic pathways in zebrafish larvae were altered following exposure to CBZ. GABA transaminase (abat) and glutamic acid decarboxylase (gad1b) decreased to 100 µg/L, and glutamate receptor, ionotropic, N-methyl D-aspartate 1b (grin1b) as well as the glutamate receptor, ionotropic, α-amino-3hydroxy-5methylisoxazole-4propionic 2b (gria2b) were down-regulated with exposure to 1 µg/L CBZ. Our study suggests that CBZ, which can act as an agonist of the GABAA receptor in humans, can also induce alterations in the GABAergic system in fish. Overall, this study improves understanding of the neurotoxicity and behavioral toxicity of zebrafish exposed to CBZ and generates data to be used to understand mechanisms of action that may underlie antiepileptic drug exposures.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping