Beyond Chronic Fatigue: Studying The Role Of Neuroinflammation, Glutamate, And Glutamine

Authors

• Indonesia Alohn Jordan, University of Alabama at Birmingham

Advisor(s)

Jarred Younger

Committee Member(s)

David Knight
Olivio Clay
Robert Sorge
Shruti Agnihotri

School

College of Arts and Sciences

Document Type

Dissertation

Department (new version)

Psychology

Date of Award

9-9-2024

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multifaceted disease characterized by persistent, severe fatigue lasting six months or longer that is not relieved by rest. An estimated 20 million people worldwide suffer from ME/CFS. ME/CFS has long been suspected to be a post-viral illness, as viral infections can stimulate inflammatory cytokine production. Millions of coronavirus disease 2019 (COVID-19) patients are also predicted to develop persistent symptoms that mimic ME/CFS symptomology after the resolution of the acute infection, referred to as Post-Acute Sequelae of COVID-19 (PASC). Inflammatory mediators produced by sustained microglia activation have been shown to lead to illness response symptoms associated with ME/CFS and PASC. Previous magnetic resonance spectroscopy imaging (MRSI) research has shown that ME/CFS patients exhibit markers of neuroinflammation, such as choline, myoinositol, and lactate. Yet, no studies have examined glutamate (Glu) and glutamine (Gln) in ME/CFS patients using MRSI. Growing evidence suggests that inflammation and alterations in the Glu-Gln cycle are linked. Prior research has also demonstrated that ME/CFS patients exhibit abnormal peripheral Glu and Gln signaling. Also, with ME/CFS involving neuroinflammation indicated by elevated brain temperature and the potential connection between ME/CFS and PASC, few studies have investigated neuroinflammation in PASC patients. This dissertation aims to explore the relationship inflammation has with Glu, Gln, and fatigue in people with ME/CFS, as well as determine if neuroinflammation is present in PASC. Using MRSI, Aim 1 established elevated Gln in the brain of ME/CFS patients compared to healthy controls. Aim 2 measured circulatory inflammation, Glu, and Gln in ME/CFS and healthy controls. We found no differences in Glu, Gln, Interlukin-6, or C-reactive protein, but Tumor Necrosis Factor-alpha was higher in the ME/CFS group. Lastly, Aim 3 demonstrated that there are signs of neuroinflammation present in PASC patients. Together, these studies indicate that dysregulation of the Glu-Gln cycle is only present centrally and that there is emerging evidence of neuroinflammation in PASC patients. These findings provide a foundation for further ME/CFS and PASC research to aid in diagnostic and treatment decisions.

ProQuest ID

https://proquest.com/docview/3101857006