Honors Theses

Date of Award

Spring 5-9-2024

Document Type

Undergraduate Thesis

Department

Biomolecular Sciences

First Advisor

Kristine Willett

Second Advisor

Joshua Bloomekatz

Third Advisor

Courtney Roper

Relational Format

Dissertation/Thesis

Abstract

Early developmental exposure to Δ9-tetrahydrocannabinol causes latent behavioral, growth, and bioenergetic effects in Danio rerio

(Under the direction of Dr. Kristine Willett)

Δ9-tetrahydrocannabinol (Δ9-THC) is used during pregnancy to mitigate symptoms such as nausea, pain, and insomnia. It is established that Δ9-THC exposure early in life causes adverse effects in children’s development including behavioral disorders. Our goal was to determine the latent and generational impacts on growth, behavior, and mitochondrial bioenergetics following exposure to Δ9-THC. Wildtype (5D) zebrafish were exposed to 0 (0.05% DMSO), 0.08, 0.4, or 1 µM Δ9-THC from 6-96 hours post-fertilization (hpf), then subsequently raised in clean water. At 6 months pf (mpf), fish from all treatments were bred to obtain the F1 generation. Both F0 and F1 zebrafish were raised and mortality, growth, and behavior were assessed at 120 hpf, and 3, 11, and 24 weeks pf (wpf). At 13-15 mpf, brains were harvested, mitochondria isolated, and oxygen consumption rate (OCR) was measured with the Seahorse Mito Stress Test. In the F0 generation, Δ9-THC (0.4 µM) caused significant hyperactivity throughout life. At 13-15 mpf, Δ9-THC (0.4 and 1 µM) significantly increased brain mitochondrial OCR in both male and female F0. The parental exposure to Δ9-THC also caused significant hyperactivity in the F1 generation at 120 hpf and 24 wpf, but not at 3 and 11 wpf. OCR was not significantly different in the F1 generation in either sex. Growth, behavior, and bioenergetics were persistently impacted in the F0 generation 15 mpf after early developmental exposure, highlighting the need for further research to determine implications of human fetal Δ9-THC exposure. This research was supported by COBRE-NPN P30 GM 122733.

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