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Sex-Specific Social Modulation of the Neuroinflammatory Response to Global Cerebral Ischemia

Gaudier-Diaz, Monica M
http://orcid.org/0000-0002-1531-864X
http://rave.ohiolink.edu/etdc/view?acc_num=osu1490713683841079

Abstract Details

2017, Doctor of Philosophy, Ohio State University, Neuroscience Graduate Studies Program.
Social isolation is a major risk factor for disease onset and progression, and has been correlated with all-cause mortality. Despite converging evidence from animal and human studies recapitulating the physiological benefits of social interaction, the mechanisms by which social environment influences health remain underspecified. In affiliative species, social isolation is a psychological stressor, capable of activating the hypothalamic pituitary adrenal (HPA) axis and altering gene expression of immune cells. These physiological changes have the potential to sensitize immune responses. The innate immune cells of the central nervous system, microglia, can become primed and will exert a prolonged and maladaptive response to additional immune stimulation. Thus, we hypothesized that social isolation can sensitize microglia, and that an exaggerated inflammatory response underlies the detrimental consequences of isolation on cerebral ischemia outcome. Increased expression of major histocompatibility II (MHC II) and a retraction of microglial processes are the most common indicators of microglial priming. Following a week of social isolation, male mice displayed increased hippocampal and cortical gene expression of MHC II, but the females did not. An elevation in the gene expression of MHC II among male mice is the first indication of isolation-induced microglial priming. When investigating social modulation of microglial reactivity to global cerebral ischemia induced by cardiac arrest/ cardiopulmonary resuscitation, social attenuation of the inflammatory response was evident at 24-hours post-ischemia in both female and male mice. Among males the ischemia-induced increase in expression of pro-inflammatory cytokines was attenuated by social interaction, whereas in the female mice pair housing ameliorated the ischemia-induced elevation of MHC II. These data suggest that social modulation over the neuroinflammatory response to global cerebral ischemia occurs regardless of biological sex, but that the underlying mechanisms are sex-specific. Following 4-days of cardiac arrest/ cardiopulmonary resuscitation, male and female mice exhibited increased locomotor activity, exploratory behavior, inflammation and cell death, relative to their sham counterparts. The ischemic effect on neuroinflammation and neurodegeneration was attenuated among the pair housed animals, demonstrating the benefits of social interaction in both females and males. Social attenuation of ischemia-induced microglial activation, characterized by reduced gene expression of pro-inflammatory cytokines in males and by lower MHC II expression among females, ameliorated long-term outcome. Our findings indicated that social isolation can alter physiology in a way that sensitizes the immune system, at least in males. Furthermore, sex-specific social modulation of the microglial response to cerebral ischemia provides insight into sexual dimorphisms in the inflammatory response to cardiac arrest/ cardiopulmonary resuscitation. Investigating sex-differences in the inflammatory response to ischemia will aid in the comprehension of the epidemiology of this heterogeneous disease and help develop effective treatment strategies.
A. Courtney DeVries (Advisor)
192 p.
Behavioral Sciences; Immunology; Neurobiology; Neurosciences
Social Isolation, Cerebral Ischemia, Microglial Priming, and Neuroinflammation

Recommended Citations

Citations

  • Gaudier-Diaz, M. M. (2017). Sex-Specific Social Modulation of the Neuroinflammatory Response to Global Cerebral Ischemia [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1490713683841079

    APA Style (7th edition)

  • Gaudier-Diaz, Monica. Sex-Specific Social Modulation of the Neuroinflammatory Response to Global Cerebral Ischemia. 2017. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1490713683841079.

    MLA Style (8th edition)

  • Gaudier-Diaz, Monica. "Sex-Specific Social Modulation of the Neuroinflammatory Response to Global Cerebral Ischemia." Doctoral dissertation, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1490713683841079

    Chicago Manual of Style (17th edition)

osu1490713683841079
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This open access ETD is published by The Ohio State University and OhioLINK.