Sex Differences of the Central Amygdala's Immune Response in EAE-Induced Chronic Pain

• Author / Creator

  Wass, Adam C

• Multiple sclerosis (MS) is an autoimmune disease that is characterized by demyelination of central nervous system axons. Symptoms of MS are highly heterogenous, although some, such as motor deficits and chronic pain, are very common in those with the disease. Defined by the International Association for the Study of Pain as pain that persists or recurs for longer than 3 months, chronic pain represents a source of significant reductions in quality of life. To date, however, the underlying mechanisms facilitating chronic pain in MS remain largely unknown. One contributor to chronic pain is the immune system, which, although shown to act differently in males and females, displays converging mechanisms of facilitation of chronic pain. To date, the majority of this work has been performed in the spinal cord, but comparatively little is known about the role of brain-resident immune cells roles in chronic pain or how these cells may influence activity within pain processing regions of the brain. This project aims to characterize the sex differences in the immune response within the central amygdala, a major hub for incoming and outgoing pain signalling. Using a murine model of MS with stereotyped pain behaviours, Experimental Autoimmune Encephalomyelitis (EAE), I demonstrate that within the amygdala, EAE induced robust cytokine dysregulation. Additionally, using the Four Core Genotype murine model, I show that the observed inflammatory dysregulation was significantly greater in animals with XX sex chromosome complement and/or ovaries. To assess if microglia were the primary drivers for this dysregulation, I assessed microglial morphology, density, and colocalization with cytokines showing sex differences, Cxcl1 and Cxcl10, and found minimal sex differences. However, astrocytes, another immunocompetent glial cell population within the brain, displayed significantly greater colocalization with tested cytokines. Furthermore, I observed a significant upregulation of Gfap+ astrocytes in the central amygdala of female EAE mice, but not males. Together, this study suggests that astrocytes may contribute to a greater extent than microglia to the sex differences in EAE-induced inflammation within the central amygdala.

• Subjects / Keywords

  • EAE
  • Pain
  • Immune
  • Sex Differences

• Graduation date

  Fall 2024

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-qn77-sj43

• License

  This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.