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ESW Thesis (9-19-13).pdf (7.19 MB)

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Stress-induced Monocyte Re-distribution and Microglia Activation Underlies Development and Recurrence of Anxiety

Wohleb, Eric S
http://rave.ohiolink.edu/etdc/view?acc_num=osu1379520096

Abstract Details

, Doctor of Philosophy, Ohio State University, Neuroscience Graduate Studies Program.
Exposure to psychological stress promotes immune dysfunction that has a significant impact on neuro-immune function. This is important because stress-induced immune alterations can lead to neuroinflammation and microglia activation that can directly influence neurobiological processes implicated in mental health disorders. The clinically relevant stress model, repeated social defeat (RSD), causes profound alterations in the inflammatory potential of peripheral myeloid cells and significantly increases their ability to traffic throughout the body, including the brain. Corresponding with enhanced monocyte trafficking in the brain RSD also promotes microglia activation in specific brain regions that mediate mood disturbances. Previous reports indicate that neuroendocrine systems, such as the sympathetic nervous system, play a prominent role in the increased inflammatory potential of peripheral myeloid cells. In particular B-adrenergic receptor signaling was implicated as propranolol pre-treatment reduced monocyte trafficking in the brain, decreased microglia activation, and prevented anxiety-like behavior following RSD (Chapter 2). To determine if RSD-induced monocyte re-distribution in the brain precipitated anxiety-like behavior CCR2KO and CX3CR1KO mice were used to limit macrophage trafficking. Increased circulating monocytes were still detected in the blood of CCR2KO and CX3CR1KO, however, these mice lacked RSD-induced macrophage trafficking in the brain which blocked development of anxiety (Chapter 3). Further studies showed that interleukin-1 (IL-1) signaling through endothelial cells mediated anxiety-like behavior after RSD (Chapter 4). These stress-induced alterations in neuro-immune function resulted in prolonged behavioral consequences following peripheral immune challenge (Chapter 5). Furthermore, RSD-induced neuroinflammation and anxiety-like behavior was transient and resolution of neuroinflammatory markers coincided with amelioration of anxiety symptoms. Despite this resiliency prior RSD exposure resulted in sensitization of neuroinflammatory and behavioral consequences. Indeed acute stress exposure incited release of monocytes from the spleen that targeted the brain and promoted anxiety-like behavior. Splenectomy prior to acute stress exposure prevented macrophage recruitment to the brain and attenuated anxiety-like behavior (Chapter 6). Taken together, these findings demonstrate that stress-induced myeloid cell trafficking in the brain and microglia activation contributes to development of anxiety-like behavior. Furthermore, these studies provide insight into neuroimmune interactions that mediate neurobiological mechanisms underlying stress-induced mood disturbances.
Jonathan Godbout (Committee Co-Chair)
John Sheridan (Committee Co-Chair)
Dana McTigue (Committee Member)
Ning Quan (Committee Member)
Susan Travers (Committee Member)
Immunology; Neurosciences; Psychology

Recommended Citations

Citations

  • Wohleb, E. S. (n.d.). Stress-induced Monocyte Re-distribution and Microglia Activation Underlies Development and Recurrence of Anxiety [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1379520096

    APA Style (7th edition)

  • Wohleb, Eric. Stress-induced Monocyte Re-distribution and Microglia Activation Underlies Development and Recurrence of Anxiety. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1379520096.

    MLA Style (8th edition)

  • Wohleb, Eric. "Stress-induced Monocyte Re-distribution and Microglia Activation Underlies Development and Recurrence of Anxiety." Doctoral dissertation, Ohio State University. Accessed APRIL 18, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=osu1379520096

    Chicago Manual of Style (17th edition)

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