Auburn Research Day 2022

B i omed i ca l Resea rch | Gr adua te/Undergr adua te St udent Covid-19 Induced Central Nervous System Disorders Differ from Other Common Viral Associated Central Nervous System Disorders

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Ramesh, Sindhu 1 ; Govindarajulu, Manoj 1 ; Tony, Thomas 1 ; Moore, Timothy 1 ; Dhanasekaran, Muralikrishnan 1 1 Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University

The emergence and spread of the severe acute respiratory syndrome corona virus type 2 (SARS-COV-2) has sent the world into a global pandemic. With over 303 million cases and over 5.4 million deaths, health care systems around the world are being strained. Viral pathogens cause a wide range of pathologies related to their primary site of infection. Intriguingly, many of these viral infections elicit symptoms associated with organ systems outside of their primary sites of infection. Of particular interest are the central nervous system (CNS) symptoms and disorders associated with SARS-CoV-2 (COVID-19). It is understood that the SARS-CoV-2 spike protein serves as a ligand for angiotensin converting enzyme-2 (ACE2) found in multiple tissues, including CNS tissues. Upon binding the spike protein undergoes proteolytic processing by protease serine 2 (TMPRSS2) to inject its RNA into a host cell. Proposed mechanisms for SARS-CoV-2 reaching the CNS include an ACE2-dependent pathway utilizing the olfactory system, infiltration from blood circulation by crossing the blood brain barrier, and access through infected immune cells. However, the specifics of COVID-19’s CNS

manifestations remain unclear. The most common CNS symptoms and disorders associated with SARS-CoV-2 include loss of smell, loss of taste, muscle weakness, dizziness, confusion, delirium, seizures, depression, anxiety, and stroke. COVID-19 causes CNS dysfunction through mechanisms different from other common viral infections such as, common flu, H1N1, hepatitis, HIV and SARS- CoV-1. The goals of the study are to compare COVID-19 induced CNS disorders and symptoms with other common viral associated CNS pathologies and to determine the mechanism(s) of COVID-19 leading to CNS symptoms and disorders. Relevant search terms contributing to the study objective were used across electronic platforms such as, PubMed, Scopus, and Google Scholar, through December 2021.

Roxana Bahani 1 , Kory Dees 3 , Kayla Kabir 3 , Rogan Sullivan 2 , Jansen Wilson 2 , Kari Dugger 1 1 Edward Via College of Osteopathic Medicine-Auburn Campus; 2 University of Alabama at Birmingham; 3 University of South Alabama B i omed i ca l Resea rch | Med i ca l St udent Physical Activity and Chronic Stress Promote Tumor Growth and Alter T-Cell Immunity 47

Triple-negative breast cancer is ~15-20% of all breast cancers, and is among the most difficult to treat. One positive prognostic biomarker for survival is high tumor infiltrating lymphocytes (TILs). Epidemiological evidence suggests psychological stress is correlated with a decrease in survival of breast cancer patients. Additionally, physical activity reduces depressive symptoms during cancer treatment prompting the question whether exercise could improve survival during cancer treatments. For this study, we investigated the effect of psychological stress (UCMS) and/ or physical activity on tumor growth and cancer immunity of mice with murine triple-negative breast cancer (EMT6). For these studies, female BALB/c mice (6-8 weeks) were subcutaneously injected with 5x105 syngeneic murine breast carcinoma cells, EMT6. Mice underwent one of 4 treatments: moderate aerobic exercise (physical stressor), unpredictable chronic mild stress (UCMS-psychological stressor), exercise + UCMS (physical and psychological stressors), or no physical/psychological stressor. Upon protocol completion, mice were examined for tumor growth and immunological changes within primary tumors. Interestingly, the no stressor controls had

significantly smaller tumors with higher CD4 + T helper (Th) and CD8 + cytotoxic T (Tc) cells within the isolated tumors as compared to all other treatment groups. In vitro studies indicate exercise increased Th and T regulatory (Treg) cell functions with or without UCMS. Exercise without UCMS increased Tc function while exercise with UCMS decreased Tc function. UCMS treatment alone mildly increased Th function, significantly decreased Treg function, and had no effect on Tc function as compared to other treatment groups. In conclusion, neither physical activity nor psychological stress decreased tumor growth, but rather increased tumor progression significantly. Notably, exercise does not appear to improve the impact of psychological stress on tumor growth or TILs. However, these studies do confirm the correlative data that increased TILs result in decreased tumor growth.

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