ABSTRACTCANNABINOID ACTION IN THE MOUSE OLFACTORY EPITHELIUMByChelsea Reed Hutch Mammalian adult neurogenesis, i.e., the lifelong generation of new neurons through progenitor stem cells, contributes to the plasticity and repair potential of the nervous system. The peripheral olfactory epithelium exhibits natural replacement of olfactory sensory neurons through the proliferation and differentiation of a local basal progenitor cell population, rendering it an ideal system with which to investigate mechanisms of neurogenesis. The cannabinoid system can influence adult neurogenesis in the central nervous system. The goal of this thesis was to investigate the role of cannabinoid signaling in promoting neurogenesis in the mouse olfactory epithelium. Both exogenous and endogenous cannabinoid signaling leads to an increase in basal cell proliferation in the mouse olfactory epithelium. Furthermore, genetically deleting both cannabinoid receptor 1 and cannabinoid receptor 2 leads to an altered olfactory epithelium composition and dysfunctional proliferation. This body of work identifies a functional cannabinoid system in the mouse olfactory epithelium for the first time, and that cannabinoids can serve as trophic factors that contribute to the regulation of tissue homeostasis. It is essential to understand the complex mechanism of olfactory epithelium progenitor cell proliferation, which could lead to future regenerative strategies using human olfactory derived progenitor cell.
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