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You searched for +publisher:"University of North Carolina" +contributor:("Walter, Thomas"). One record found.

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University of North Carolina

1. Walter, Thomas. Ethanol and Microglia: From Molecules to Behavior.

Degree: Pharmacology, 2017, University of North Carolina

Alcohol use disorders (AUDs) are prevalent mental health conditions involving problematic alcohol use despite negative consequences. Available treatments for AUDs are often unhelpful, prompting a search for more effective medications. Interestingly, recent research has identified a role for the neuroimmune system in AUDs, suggesting therapies targeting immune signaling may be helpful. Microglia are the most prominent cell type of the neuroimmune system and are implicated in AUDs. Indeed, alcohol activates microglia. Stress – believed to play a critical role in AUDs – also activates microglia. Alcohol and stress are thought to activate microglia by increasing leakage of bacterial products such as endotoxins from the gut. This causes peripheral inflammation that impacts the neuroimmune system and activates microglia. However, the significance of this microglial activation is unclear. Indeed, microglial activation has multiple functional outcomes ranging from pro-inflammatory and destructive to anti-inflammatory and healing. Microglia can also affect neuronal activity and influence behavior. Understanding how alcohol and stress impact microglia and how this affects the brain and behavior may provide critical insights into the mechanisms of AUDs. In this dissertation, we investigate the relationship between microglia and AUDs. We used microglial-cell culture models and animal models to investigate the effects of ethanol on microglia. We also used the microglial-depleting compound PLX5622 to study the role of microglia in the effects of ethanol. We find that acute ethanol withdrawal increased microglial pro-inflammatory cytokine expression (TNFα, Ccl2) in vitro and in vivo, and that microglial depletion blunted the brain pro-inflammatory response (TNFα, Ccl2) and enhanced the brain anti-inflammatory response (IL-1ra, IL-4) to acute ethanol withdrawal. Furthermore, simultaneous exposure to acute ethanol and acute stress enhanced plasma endotoxin and increased the microglial marker CD11b in multiple brain regions. Chronic intermittent ethanol persistently enhanced stress-induced plasma endotoxin and microglial CD11b across the brain. Finally, microglial depletion blunted the neuronal c-Fos response to acute ethanol withdrawal in some brain regions and decreased voluntary ethanol consumption over time. Overall, these results implicate microglia in AUDs, suggesting therapies that target immune signaling may aid treatment. Advisors/Committee Members: Walter, Thomas, Crews, Fulton, Garbutt, James, Kash, Thomas, Nicholas, Robert, Robinson, Donita, University of North Carolina at Chapel Hill.

Subjects/Keywords: School of Medicine; Department of Pharmacology

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APA (6th Edition):

Walter, T. (2017). Ethanol and Microglia: From Molecules to Behavior. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:e4a31f62-4b30-4145-a953-9ff09b65a500

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Walter, Thomas. “Ethanol and Microglia: From Molecules to Behavior.” 2017. Thesis, University of North Carolina. Accessed October 30, 2020. https://cdr.lib.unc.edu/record/uuid:e4a31f62-4b30-4145-a953-9ff09b65a500.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Walter, Thomas. “Ethanol and Microglia: From Molecules to Behavior.” 2017. Web. 30 Oct 2020.

Vancouver:

Walter T. Ethanol and Microglia: From Molecules to Behavior. [Internet] [Thesis]. University of North Carolina; 2017. [cited 2020 Oct 30]. Available from: https://cdr.lib.unc.edu/record/uuid:e4a31f62-4b30-4145-a953-9ff09b65a500.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Walter T. Ethanol and Microglia: From Molecules to Behavior. [Thesis]. University of North Carolina; 2017. Available from: https://cdr.lib.unc.edu/record/uuid:e4a31f62-4b30-4145-a953-9ff09b65a500

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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