Abstract
Consumption of cannabinoid-containing products is on the rise, even during pregnancy. Unfortunately, the long-term, age-related consequences of developmental cannabidiol (CBD) exposure remain largely unknown. This is a critical gap given the established Developmental Origins of Health and Disease (DOHaD) paradigm which emphasizes that stressors, like drug exposure, early in life can instigate molecular and cellular changes that ultimately lead to adverse outcomes later in life. Thus, we exposed zebrafish (Danio rerio) to varying concentrations of CBD (0.02, 0.1, 0.5 μM) during larval development and assessed aging in both the F0 (exposed generation) and their F1 offspring 30 months later. F0 exposure to CBD significantly increased survival (~ 20%) and reduced size (wet weight and length) of female fish. While survival was increased, the age-related loss of locomotor function was unaffected and the effects on fecundity varied by sex and dose. Treatment with 0.5 μM CBD significantly reduced sperm concentration in males, but 0.1 μM increased egg production in females. Similar to other model systems, control aged zebrafish exhibited increased kyphosis as well as increased expression markers of senescence, and inflammation (p16ink4ab, tnfα, il1b, il6, and pparγ) in the liver. Exposure to CBD significantly reduced the expression of several of these genes in a dose-dependent manner relative to the age-matched controls. The effects of CBD on size, gene expression, and reproduction were not reproduced in the F1 generation, suggesting the influence on aging was not cross-generational. Together, our results demonstrate that developmental exposure to CBD causes significant effects on the health and longevity of zebrafish.
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Acknowledgments
The authors would like to thank Dennis R. Carty for conducting the initial exposure, as well as Kennedy E. Dickson, Mary-Beth Gillespie, James H. Gledhill, Haley Watts, and Bailey Westling for their help during sampling.
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This work was supported by the National Institute on Drug Abuse R21DA044473-01 grant awarded to KW and P30GM122733 to NMA and KW.
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KW, NA, and ZP conceived and designed the experiments; NA and ZP analyzed the data; AF, AW, CT, NA, and ZP performed the experiments; and KW, NA, and ZP prepared the manuscript.
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Pandelides, Z., Thornton, C., Faruque, A.S. et al. Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio). GeroScience 42, 785–800 (2020). https://doi.org/10.1007/s11357-020-00182-4
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DOI: https://doi.org/10.1007/s11357-020-00182-4