Chronic Olfactory Epithelial Inflammation Impairs the Olfactory Bulb
Location
D.P. Culp Center Ballroom
Start Date
4-5-2024 9:00 AM
End Date
4-5-2024 11:30 AM
Poster Number
77
Name of Project's Faculty Sponsor
Jia Cuihong
Faculty Sponsor's Department
Biomedical Sciences
Competition Type
Competitive
Type
Poster Presentation
Presentation Category
Health
Abstract or Artist's Statement
The function of smell depends on olfactory sensory neurons (OSNs) in the olfactory epithelium (OE). The OSNs project their axons to the olfactory bulb (OB) that directly connects to brain areas related to emotional regulation, learning, and memory. Chronic OE inflammation destroys all of the OSNs in mouse OE, leading to anosmia. SARS-CoV-2 causes OE inflammation by targeting non-neuronal sustentacular cells. Thus, inflammation-induced loss of OSNs could be one of the leading causes of anosmia/hyposmia in COVID-19 patients. However, up to 50 percent of COVID-19 patients also develop symptoms related to the central nervous system, including encephalopathy, stroke, seizure, and Guillan-Barré syndrome. Given the OB anatomical location, we hypothesized that chronic OE inflammation impairs the OB, affecting brain function. The inducible olfactory inflammation model was used to express TNF-α in the sustentacular cells using the Tet-on system and doxycycline. Following 4-6 weeks of doxycycline treatment, TNF-α mRNA levels in the OE tissue measured by RT-qPCR were increased 500 to 1000-fold, and TNF-α protein in the nasal lavage measured by ELISA was increased 15-fold in both female and male mice. Cytokines and chemokines, including IL-6, IL-1b, IFNγ, and CCL2, were also dramatically elevated, confirming massive OE inflammation in our model. In the OB, we found that IL-6 and IL-1β mRNA were up-regulated, while TNF-α, IFNγ and CCL2 were not altered in either sex, suggesting that chronic OE inflammation causes OB inflammation but with a different profile. The OB inflammation was also confirmed by increased microglia activation (CD68) and infiltrated leukocytes (CD45). Future studies will investigate the mechanisms underlying OB inflammation and how OB inflammation affects brain functions. Together, these findings will help us better understand the pathophysiology of COVID-19 and nasal inflammation, such as chronic rhinosinusitis.
Chronic Olfactory Epithelial Inflammation Impairs the Olfactory Bulb
D.P. Culp Center Ballroom
The function of smell depends on olfactory sensory neurons (OSNs) in the olfactory epithelium (OE). The OSNs project their axons to the olfactory bulb (OB) that directly connects to brain areas related to emotional regulation, learning, and memory. Chronic OE inflammation destroys all of the OSNs in mouse OE, leading to anosmia. SARS-CoV-2 causes OE inflammation by targeting non-neuronal sustentacular cells. Thus, inflammation-induced loss of OSNs could be one of the leading causes of anosmia/hyposmia in COVID-19 patients. However, up to 50 percent of COVID-19 patients also develop symptoms related to the central nervous system, including encephalopathy, stroke, seizure, and Guillan-Barré syndrome. Given the OB anatomical location, we hypothesized that chronic OE inflammation impairs the OB, affecting brain function. The inducible olfactory inflammation model was used to express TNF-α in the sustentacular cells using the Tet-on system and doxycycline. Following 4-6 weeks of doxycycline treatment, TNF-α mRNA levels in the OE tissue measured by RT-qPCR were increased 500 to 1000-fold, and TNF-α protein in the nasal lavage measured by ELISA was increased 15-fold in both female and male mice. Cytokines and chemokines, including IL-6, IL-1b, IFNγ, and CCL2, were also dramatically elevated, confirming massive OE inflammation in our model. In the OB, we found that IL-6 and IL-1β mRNA were up-regulated, while TNF-α, IFNγ and CCL2 were not altered in either sex, suggesting that chronic OE inflammation causes OB inflammation but with a different profile. The OB inflammation was also confirmed by increased microglia activation (CD68) and infiltrated leukocytes (CD45). Future studies will investigate the mechanisms underlying OB inflammation and how OB inflammation affects brain functions. Together, these findings will help us better understand the pathophysiology of COVID-19 and nasal inflammation, such as chronic rhinosinusitis.