Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


osu1313082975.pdf (5.92 MB)

ETD Abstract Container

Abstract Header

Regulation of Microglia in the Brain by Fractalkine Signaling: Implications for Inflammation-Associated Sickness and Depression

Corona, Angela Wynne
http://rave.ohiolink.edu/etdc/view?acc_num=osu1313082975

Abstract Details

2011, Doctor of Philosophy, Ohio State University, Neuroscience Graduate Studies Program.
Impaired immunoregulation with aging predisposes the elderly to cognitive and neurobehavioral deficits. The complex communication between the peripheral and neuroimmune systems is incompletely understood, but growing evidence shows there are profound implications for neuroinflammation and regulation of cognitive processes. For example, aging is associated with increased reactivity and dysregulation of microglia, the innate immune cells of the central nervous system. Dsyregulation of microglial activation is paralleled by prolonged sickness, depressive-like complications, and cognitive impairment. Fractalkine (CX3CL1) to fractalkine receptor (CX3CR1) interactions in the brain are involved in the modulation of microglial activation. CX3CL1 is a chemokine that is highly expressed by neurons, while CX3CR1 is expressed by microglia. CX3CL1-CX3CR1 mediated regulation of microglia was impaired in the brain of aged Balb/c mice following a peripheral immune challenge with lipopolysaccharide (LPS). Specifically, there was reduced CX3CL1 protein in the cortex of aged mice and prolonged downregulation of CX3CR1 on the surface of microglia (Chapter 2). To determine if the impaired CX3CL1-CX3CR1 interactions were sufficient to cause prolonged neurobehavioral deficits, adult CX3CR1-/- mice were used. CX3CR1-/- mice showed prolonged sickness and depressive-like behaviors compared with CX3CR1-/+ mice following an LPS challenge that was coupled with exaggerated and prolonged microglial activation (Chapter 3). CX3CR1-deficiency was also associated with an exaggerated induction of indoleamine-2,3,-dioxygenase (IDO). To determine the role of IDO in the prolonged neurobehavioral deficits in CX3CR1-/- mice, IDO was blocked using 1- methyl tryptophan (1-MT) before the LPS challenge. 1-MT had no effect on saline treated mice, or on CX3CR1-/+ mice. 1-MT pretreatment in CX3CR1-/- mice, however, blocked the LPS-induced prolonged depressive-like behavior and microglial activation compared with placebo treated CX3CR1-/- mice (Chapter 4). Thus, CX3CR1-deficiency leads to exaggerated induction of IDO, which at least partially underlies the prolonged depressive-like symptoms following LPS injection. Taken together, these data indicate that impaired CX3CL1-CX3CR1 mediated regulation of microglia is involved in the age-related susceptibility to neurobehavioral deficits following an immune challenge.
Jonathan P. Godbout (Advisor)
John S. Sheridan (Committee Member)
Andrew J. Fischer (Committee Member)
Phillip G. Popovich (Committee Member)
Ning Quan (Committee Member)
A. Courtney DeVries (Committee Member)
153 p.
Immunology; Neurosciences
aging; neuroinflammation; fractalkine; fractalkine receptor; microglia; psychoneuroimmunology

Recommended Citations

Citations

  • Corona, A. W. (2011). Regulation of Microglia in the Brain by Fractalkine Signaling: Implications for Inflammation-Associated Sickness and Depression [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1313082975

    APA Style (7th edition)

  • Corona, Angela. Regulation of Microglia in the Brain by Fractalkine Signaling: Implications for Inflammation-Associated Sickness and Depression. 2011. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1313082975.

    MLA Style (8th edition)

  • Corona, Angela. "Regulation of Microglia in the Brain by Fractalkine Signaling: Implications for Inflammation-Associated Sickness and Depression." Doctoral dissertation, Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1313082975

    Chicago Manual of Style (17th edition)

osu1313082975
1,385
© 2011, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.