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Using a Mouse Model to Explore the Neuroprotective Potential of Cannabidiol

Camilla May
Florida State University

Co-Authors: Ashley Mae Loeven1, Alexis Cox1, Debra Ann Fadool1
1Florida State University

As the medicalization of marijuana occurs across the U.S., the main non-psychoactive component cannabidiol (CBD), has gained recognition for its therapeutic potential. Studies have explored the therapeutic ability of CBD in the treatment of certain neurodegenerative diseases or traumatic brain injury. We and others have reported a link between fatty diet consumption and increased neuronal loss and neuroinflammation in the olfactory and taste systems of mice. The objective for my project, therefore, was to assess the potential of CBD to mitigate neuroinflammation and neuronal loss induced by diet-induced obesity. Mice used in this study (OMPtauGFP) expressed GFP restricted to mature olfactory sensory neurons (OSNs). One-month old mice of both sexes were weaned to moderately high-fat (MHF) diet (32% kcals from fat) and received 20 mg/kg CBD or vehicle by intraperitoneal injection every weekday for four weeks. Mice were fix-perfused, and their brains were post-fixed and cryoprotected. The main olfactory epithelium (MOE) was cryosectioned at 16 µm thickness; the sections were collected on slides and processed for immunohistochemistry. The MOE sections were incubated with antibodies associated with inflammation (anti-Iba-1) and cell proliferation (anti-Ki67), while the endogenous GFP marked mature OSN abundance. The sections were imaged on a Zeiss microscope (Axiovert S 100) to quantify the number of OSNs that were positive for these antigens. Photomicrographs were acquired from the septal region of the MOE. CBD-treated mice had greater abundance of GFP+ OSNs in the MOE, regardless of sex (Student’s t-test p = 0.0159). There was no significant difference in the abundance of Ki67+ or Iba-1+ cells, however, across drug treatment groups (Student’s t-test, p > 0.05). We conclude that CBD treatment of MHF-fed mice induced neuroprotection without observed changes in neuroinflammation or cell proliferation as indicated by these markers. Planned acquisition of additional MOE regions will expand the interpretation or universality of our findings. Whether CBD can reverse the deleterious effects of obesity, rather than prevent it, is being explored in a separate cohort of mice maintained on the MHF diet for 3 months prior to beginning CBD treatment.

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