PUBLICATION
Multigenerational consequences of early-life cannabinoid exposure in zebrafish
- Authors
- Carty, D.R., Miller, Z.S., Thornton, C., Pandelides, Z., Kutchma, M.L., Willett, K.L.
- ID
- ZDB-PUB-181231-2
- Date
- 2018
- Source
- Toxicology and applied pharmacology 364: 133-143 (Journal)
- Registered Authors
- Keywords
- Behavior, Cannabidiol, Development, Multigenerational, Tetrahydrocannabinol, Zebrafish
- MeSH Terms
-
- Age Factors
- Animals
- Animals, Genetically Modified
- Behavior, Animal/drug effects
- Brain/drug effects*
- Brain/embryology
- Brain/metabolism
- Brain-Derived Neurotrophic Factor/genetics
- Brain-Derived Neurotrophic Factor/metabolism
- Cannabidiol/toxicity*
- Dronabinol/toxicity*
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Fertility/drug effects
- Fertility/genetics
- Gene Expression Regulation, Developmental/drug effects*
- Motor Activity/drug effects
- Neurotoxicity Syndromes/embryology
- Neurotoxicity Syndromes/genetics*
- Neurotoxicity Syndromes/metabolism
- Proto-Oncogene Proteins c-fos/genetics
- Proto-Oncogene Proteins c-fos/metabolism
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism
- Risk Assessment
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 30594692 Full text @ Tox. App. Pharmacol.
- CTD
- 30594692
Citation
Carty, D.R., Miller, Z.S., Thornton, C., Pandelides, Z., Kutchma, M.L., Willett, K.L. (2018) Multigenerational consequences of early-life cannabinoid exposure in zebrafish. Toxicology and applied pharmacology. 364:133-143.
Abstract
While Δ9-tetrahydrocannabinol (THC) has been widely studied in the realm of developmental and reproductive toxicology, few studies have investigated potential toxicities from a second widely used cannabis constituent, cannabidiol (CBD). CBD is popularized for its therapeutic potential for reducing seizure frequencies in epilepsy. This study investigated developmental origins of health and disease (DOHaD) via multigenerational gene expression patterns, behavior phenotypes, and reproductive fitness of a subsequent F1 following an F0 developmental exposure of zebrafish (Danio rerio) to THC (0.024, 0.12, 0.6 mg/L; 0.08, 0.4, 2 μM) or CBD (0.006, 0.03, 0.15 mg/L; 0.02, 0.1, 0.5 μM). Embryonic exposure at these concentrations did not cause notable morphological abnormalities in either F0 or F1 generations. However, during key developmental stages (14, 24, 48, 72, and 96 h post fertilization) THC and CBD caused differential expression of c-fos, brain-derived neurotrophic factor (bdnf), and deleted-in-azoospermia like (dazl), while in F1 larvae only CBD differentially expressed dazl. Larval photomotor behavior was reduced (F0) or increased (F1) by THC exposure, while CBD had no effect on F0 larvae, but decreased activity in the unexposed F1 larvae. These results support our hypothesis of cannabinoid-related developmental neurotoxicity. As adults, F0 fecundity was reduced, but this was not in F1 adults. Conversely, in the adult open field test there were no significant effects in F0 fish, but a significant reduction in the time in periphery was seen in F1 s from the highest THC exposure group. The results highlight the need to consider long-term ramifications of early-life exposure to cannabinoids.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping