Influence of sex hormones on the endocannabinoid system in response to chronic intermittent hypoxia
Description
Chronic intermittent hypoxia (CIH), a well-established model of sleep apnea (SA), elicits sympathetic activation, oxidative stress, inflammation, endothelial dysfunction, and metabolic dysregulation. The endocannabinoid system (eCS) has emerged as a potential modulator of these processes. The CB2 receptor demonstrates protective and anti-inflammatory effects, partly through NRF2 activation of the antioxidant response element in the CB2 promoter. Furthermore, evidence suggests protective effects of estrogen in response to CIH, but research is required to clarify the role of sex hormones in the eCS system in the context of CIH. In this study, adult female Sprague Dawley rats (n=23) underwent either ovariectomy (n=12) or sham (n=11). After 4 weeks of recovery, the rats were exposed to CIH (60 sec. FiO2 10%, 120 sec. FiO2 21%) (n=11) or sham (21% FiO2) (n=12) for 8 hours per day for 14 days. Renal cortex and medulla samples were excised, and then RNA was isolated from these tissues. qPCR was performed on cDNA generated from the RNA to characterize the expression of the CB1, CB2, NRF2, and KEAP1 genes. This experiment directly assesses sex-dependent modulation of the NRF2-CB2 axis under hypoxic stress. By understanding these differences, we can elucidate mechanisms linking SA to chronic kidney disease and potentially identify NRF2 and CB2 as potential therapeutic targets.
Citation Information
Watson, Jackson; Lin, Emma; Lombardi Labegaline, Julia; Clark, Emmaly; Giles, Jennifer; Marcus, Noah; and Clayton, Sarah, "Influence of sex hormones on the endocannabinoid system in response to chronic intermittent hypoxia" (2026). Office of Research DMU Research Symposium. 88.
https://digitalcommons.dmu.edu/researchsymposium/2025rs/2025abstracts/88
Influence of sex hormones on the endocannabinoid system in response to chronic intermittent hypoxia
Chronic intermittent hypoxia (CIH), a well-established model of sleep apnea (SA), elicits sympathetic activation, oxidative stress, inflammation, endothelial dysfunction, and metabolic dysregulation. The endocannabinoid system (eCS) has emerged as a potential modulator of these processes. The CB2 receptor demonstrates protective and anti-inflammatory effects, partly through NRF2 activation of the antioxidant response element in the CB2 promoter. Furthermore, evidence suggests protective effects of estrogen in response to CIH, but research is required to clarify the role of sex hormones in the eCS system in the context of CIH. In this study, adult female Sprague Dawley rats (n=23) underwent either ovariectomy (n=12) or sham (n=11). After 4 weeks of recovery, the rats were exposed to CIH (60 sec. FiO2 10%, 120 sec. FiO2 21%) (n=11) or sham (21% FiO2) (n=12) for 8 hours per day for 14 days. Renal cortex and medulla samples were excised, and then RNA was isolated from these tissues. qPCR was performed on cDNA generated from the RNA to characterize the expression of the CB1, CB2, NRF2, and KEAP1 genes. This experiment directly assesses sex-dependent modulation of the NRF2-CB2 axis under hypoxic stress. By understanding these differences, we can elucidate mechanisms linking SA to chronic kidney disease and potentially identify NRF2 and CB2 as potential therapeutic targets.
