WORMS GET THE MUNCHIES: ENDOCANNABINOID MODULATION OF FEEDING AND CHEMOSENSATION IN C. ELEGANS
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Date
2022-10-04
Authors
Levichev, Anastasia
Journal Title
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Publisher
University of Oregon
Abstract
The ability of Cannabis sativa to stimulate appetite has been known for centuries. This effect results from the action of plant-derived cannabinoids at cannabinoid receptors in the brain where they mimic natural ligands called endocannabinoids. The endocannabinoid system contributes to many physiological functions in the body, including energy homeostasis. Although cannabinoid signaling is widely conserved across the animal kingdom, the degree of functional conservation, particularly in non-mammals remains an open question. This work explores the role of the endocannabinoid system in modulating food intake across species, with particular focus on the nematode worm C. elegans. Exposure to anandamide, an endocannabinoid common to nematodes and mammals, selectively increases C. elegans’ consumption of nutritionally superior, highly palatable food without a concomitant increase in consumption of non-palatable food—a pattern of altered preferences analogous to that of mammals in response to cannabinoids. Anandamide’s effect on feeding requires the worm’s cannabinoid receptor NPR-19. Moreover, the NPR-19 receptor can be replaced by human CB1 receptor, indicating a robust functional homology between the function of the endocannabinoid systems of mammals and nematodes. Anandamide’s effect requires a single pair of primary chemosensory neurons, AWC, whose response to anandamide is sufficient to explain its effects on food preference. These findings establish a surprising degree of conservation in appetitive behaviors and establish C. elegans as model system in which to investigate the cellular and molecular basis of endocannabinoid system function.
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Keywords
AWC, cannabinoid, elegans, feeding, hedonic, olfaction