Multigenerational consequences of early-life cannabinoid exposure in zebrafish
| Autor: | Dennis R. Carty, Cammi Thornton, Marisa L. Kutchma, Zacharias Pandelides, Kristine L. Willett, Zachary S. Miller |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Embryo Nonmammalian medicine.medical_treatment Danio Physiology Motor Activity Toxicology Risk Assessment Article Open field Animals Genetically Modified 03 medical and health sciences DAZL 0302 clinical medicine medicine Animals Cannabidiol Dronabinol Tetrahydrocannabinol Zebrafish Pharmacology Behavior Animal biology Brain-Derived Neurotrophic Factor Age Factors Brain Gene Expression Regulation Developmental RNA-Binding Proteins Zebrafish Proteins biology.organism_classification Fertility 030104 developmental biology 030220 oncology & carcinogenesis Neurotoxicity Syndromes Cannabis Cannabinoid Proto-Oncogene Proteins c-fos medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 364:133-143 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2018.12.021 |
| Popis: | 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 it 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 fish from the highest THC exposure group. The results highlight the need to consider long-term ramifications of early-life exposure to cannabinoids. |
| Databáze: | OpenAIRE |
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