Defense Date

6-6-2022

Graduation Date

Summer 8-13-2022

Availability

One-year Embargo

Submission Type

dissertation

Degree Name

PhD

Department

Pharmacology-Toxicology

School

School of Pharmacy

Committee Chair

Lauren A. O'Donnell

Committee Member

Rehana K. Leak

Committee Member

David A. Johnson

Committee Member

Benedict Kolber

Committee Member

Amy Hartman

Keywords

neural stem cells, virus, measles, adult, neurogenesis, brain, behavior, immune, anti-viral

Abstract

Viral infections in the central nervous system (CNS) are associated with neurodevelopmental and neurobehavioral deficits. The outcomes of viral infections can be driven by damage and death of neurons. Neural stem cells (NSCs) play key roles in neurodevelopment, repair, and physiological brain function. During a viral infection, NSC activity can disturbed by direct infection of NSCs by the virus or by anti-viral immune response. Here, we aimed to assess whether the anti-viral immune response can impact NSC activity during an immunocompetent response in the adult brain. We utilized a transgenic mouse model of Measles virus infection where only the CNS neurons are infected sparing the NSCs from infection. Thus, we assessed the effects of the anti-viral immune response on NSCs in the adult brain during a viral infection. NSC activity was altered in the adult brain despite successful control of the infection. However, these cellular changes in NSC activity were not accompanied with behavioral changes. These changes in NSC activity could be associated with the adaptive immune system and the anti-viral cytokine, interferon-γ. Neonatal NSCs responded differently during a viral infection as compared to adult NSCs. We identified age-dependent physiological differences in the JAK-STAT pathway proteins in NSCs. Thus, we concluded that the adult brain is resilient to the infection and the changes in NSC activity might be a protective mechanism. However, further studies are required to better understand the role of age and the involvement of individual immune components that may be involved in manipulating NSC activity.

Language

English

Additional Citations

Chandwani MN, Creisher PS, O'Donnell LA. Understanding the Role of Antiviral Cytokines and Chemokines on Neural Stem/Progenitor Cell Activity and Survival. Viral Immunol. 2019 Jan/Feb;32(1):15-24. doi: 10.1089/vim.2018.0091. Epub 2018 Oct 10. PMID: 30307795; PMCID: PMC6350063.

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