Multi-Generational Effects of ∆9-Tetrahydrocannabinol Exposure on Gene Expression in Liver Tissue
Date of Award
Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ9-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired fecundity. Treatment with the lowest dose of THC also significantly reduced wet weight, the incidence of kyphosis, and the expression of several senescence and inflammatory markers (p16, tnfα, il-1β, il-6, pparα, and pparγ) in the liver, but not at higher doses. Within the F1 generation, many of these changes were not observed, such as the changes in gene expression in genes related to cell senescence and inflammation. However, the reduction in fecundity due to THC exposure was adversely impacted in the F1 generation, because offspring whose parents received a high dose of THC were completely unable to reproduce. Together, our results demonstrate that a developmental exposure to THC can cause significant effects on longevity and health span of zebrafish in a dose-dependent biphasic manner.
Lovitt, Kayla, "Multi-Generational Effects of ∆9-Tetrahydrocannabinol Exposure on Gene Expression in Liver Tissue" (2020). Honors Theses. 1340.
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