Date of Award

Spring 1-1-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Christopher A. Lowry

Second Advisor

Serge Campeau

Third Advisor

Pei-San Tsai

Fourth Advisor

Robert L. Spencer

Fifth Advisor

Benjamin Greenwood

Abstract

The "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to microorganisms that drive immunoregulatory circuits and a failure to terminate inappropriate inflammatory responses. Inappropriate inflammation is also emerging as a risk factor for anxiety disorders, affective disorders, and trauma-and stressor-related disorders, including posttraumatic stress disorder (PTSD), which is characterized as persistent re-experiencing of the trauma after a traumatic experience. Traumatic experiences can lead to long-lasting fear memories and fear potentiation of the acoustic startle reflex. Mycobacterium vaccae is a soil-derived bacterium with anti-inflammatory and immunoregulatory properties that has demonstrated to increase stress resilience in a mouse model of PTSD. To determine if immunizations with M. vaccae NCTC 11659 also has protective effects in a fear-potentiated startle paradigm, male adult Sprague Dawley rats were immunized with M.vaccae (0.1 mg, s.c., in 100 uL borate-buffered saline) or vehicle. Additionally, we tested whether M. vaccae immunization given after fear conditioning would have protective effects in a fear-potentiated startle paradigm. Finally, it was determined if M. vaccae would also have protective effects in additional Pavlovian fear conditioning paradigms involving stress-induced exaggeration of fear and resistance to fear extinction. Together with previous studies, these data are consistent with the hypothesis that anti-inflammatory and immunoregulatory strategies, such as immunization with M. vaccae, have potential for both prevention and treatment of trauma- and stressor-related psychiatric disorders.

Available for download on Thursday, May 13, 2021

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