Post-Exertional Malaise in Dauer Caenorhabditis elegans as a Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract

COVID-19 significantly impacted human health globally, with consequences that continue well beyond the pandemic. It has left 17% of the United States’ adult population with long COVID, a condition with symptoms that include those similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Key characteristics of ME/CFS include metabolic reductions, changes in brain morphology, and, namely, post-exertional malaise (PEM). The biological underpinnings of the syndrome are largely unknown, and research in humans has been limited. While other animal models rely on complex interventions to induce ME/CFS-like symptoms, Caenorhabditis elegans (C. elegans) naturally transition into dauer, a unique developmental stage that is hypothesized to parallel the metabolic reductions and lethargy found in individuals with ME/CFS. My thesis aims to investigate the behavioral changes occurring in C. elegans post-exertion, using the dauer stage as a model for humans with ME/CFS. Developed is a behavioral swim assay aimed to trigger PEM in dauer C. elegans and non-dauer counterparts. Also developed is a modified high-throughput computer vision assisted behavioral assay, utilized to track multiple C. elegans at once post-exertion. Findings suggest that dauer C. elegans experience PEM to a greater extent than non-dauer C. elegans. Dauer C. elegans exhibited reduced movement post-exertion relative to non-dauer C. elegans, visible both over the five-day behavioral assay and on a day-to-day basis. Additionally, exercised dauer C. elegans showed less spatial deviation from their starting point over time compared to controls. Thus, these findings propose that dauer C. elegans may serve as a useful developmental stage for investigating aspects of PEM relevant to ME/CFS.