Developing a Better Animal Model of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a rare but extremely debilitating disease characterized by severe fatigue, even after only mild exertion. In fact, ¼-⅓ of patients are house- or bedridden, underscoring the urgent need for effective treatment. Patients with ME/CFS display hypocortisolism, overactive serotonergic systems, and elevated TGF-β levels, suggesting that ME/CFS includes dysfunction of the endocrine, nervous, and immune systems. Current animal models of ME/CFS use immune activators but lack the complex multisystemic nature of the disease and bear a closer resemblance to depression than ME/CFS. One recent study showed that an adrenalectomy (ADX) better matched the characteristics seen in patients with ME/CFS, reducing cortisol levels and increasing serotonergic tone and TGF-β levels in mice. We aim to combine ADX and immune activation in rats, providing a new and improved rodent model of ME/CFS. Rats will undergo ADX or sham surgeries and receive either an immune activator or vehicle injections. Then, each rat will be tested for pain sensitivity, muscular strength, fatigue, depressive and anxious behaviors, as well as glucocorticoid levels, serotonergic activity, and TGF-β levels. We predict that ADX will replicate disease features better than immune activation, but we hypothesize that ADX will interact with immune activation, together bringing about disease-related outcomes that more closely replicate features of ME/CFS than either one does alone. If so, this new model will provide opportunities to test potential therapeutic targets that could help ameliorate symptoms for patients with ME/CFS.
Faculty Sponsors
Dr. Travis Craddock, Dr. Mary (Allie) Holschbach
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Developing a Better Animal Model of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Alvin Sherman Library
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a rare but extremely debilitating disease characterized by severe fatigue, even after only mild exertion. In fact, ¼-⅓ of patients are house- or bedridden, underscoring the urgent need for effective treatment. Patients with ME/CFS display hypocortisolism, overactive serotonergic systems, and elevated TGF-β levels, suggesting that ME/CFS includes dysfunction of the endocrine, nervous, and immune systems. Current animal models of ME/CFS use immune activators but lack the complex multisystemic nature of the disease and bear a closer resemblance to depression than ME/CFS. One recent study showed that an adrenalectomy (ADX) better matched the characteristics seen in patients with ME/CFS, reducing cortisol levels and increasing serotonergic tone and TGF-β levels in mice. We aim to combine ADX and immune activation in rats, providing a new and improved rodent model of ME/CFS. Rats will undergo ADX or sham surgeries and receive either an immune activator or vehicle injections. Then, each rat will be tested for pain sensitivity, muscular strength, fatigue, depressive and anxious behaviors, as well as glucocorticoid levels, serotonergic activity, and TGF-β levels. We predict that ADX will replicate disease features better than immune activation, but we hypothesize that ADX will interact with immune activation, together bringing about disease-related outcomes that more closely replicate features of ME/CFS than either one does alone. If so, this new model will provide opportunities to test potential therapeutic targets that could help ameliorate symptoms for patients with ME/CFS.
