Investigating the Effects of Activating the Endocannabinoid System during Zebrafish Embryonic Development
Sciences and Mathematics, College of
Biology, Department of
BURS Faculty Advisor
The Endocannabinoid system is a neuromodulatory system that consists of endocannabinoids, cannabinoid receptors, and the enzymes responsible for the synthesis and degradation of endocannabinoids.1 Endocannabinoids are lipid messengers that act as retrograde neurotransmitters. They target the cannabinoid receptors CB1 and CB2 in humans and cnr1 and cnr2 in zebrafish. The endocannabinoid system plays a crucial role in developing the central nervous system. For example, “the presence of CB1 receptor at early developmental stages suggests that the eCBs contribute to CNS development, such as axonal elongation, myelination, migration, cell proliferation, and synaptogenesis” (Fernandez-Ruiz et al. 2000).2 Prior research has shown that the expression of the CB1 receptor is primarily detected during prenatal development and is almost nonexistent in the adult brain.2 This suggests that the endocannabinoid system plays a significant role in neural development in humans. If it is damaged or the receptors are not expressed, it could impact the embryo’s development.2 There is little research conducted on the effect of the endocannabinoid system on embryonic human development. This is a cause for concern, considering the increase of pregnant women using cannabis products to treat their negative pregnancy symptoms. Our research investigates the effects of the activation of the endocannabinoid system during embryonic development in zebrafish, specifically the role of cnr1 and cnr2 receptors in zebrafish embryonic development. We treated embryos with a synthetic cannabinoid known as WIN. WIN is a synthetic cannabinoid that acts as an agonist on both the CB1 and CB2 receptors, meaning it still produces a similar response even though it is the synthetic version of that chemical. In our experiment, we treated zebrafish embryos with WIN at different times after fertilization to see if any developmental changes occurred. We saw perturbations to zebrafish development in the form of a shortened anterior-posterior axis and an altered hatching rate. We can correlate the findings back to human development because zebrafish and humans have many similarities, including cannabinoid receptors.
1. Lu, H. C., & Mackie, K. (2016). An Introduction to the Endogenous Cannabinoid System. Biological psychiatry, 79(7), 516–525. https://doi.org/10.1016/j.biopsych.2015.07.028 2. Oltrabella, F., Melgoza, A., Nguyen, B., & Guo, S. (2017). Role of the endocannabinoid system in vertebrates: Emphasis on the zebrafish model. Development, growth & differentiation, 59(4), 194–210. https://doi.org/10.1111/dgd.12351