title: Tumor growth increases neuroinflammation, fatigue and depressive-like behavior prior to alterations in muscle function.
abstract: Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor growth increased fatigue- and depressive-like behaviors, and reduced body and muscle mass. Decreased voluntary wheel running activity (VWRA) and increased depressive-like behavior in the forced swim and sucrose preference tests were evident in tumor-bearing mice within the first two weeks of tumor growth and preceded the loss of body and muscle mass. At three weeks, tumor-bearing mice had reduced grip strength but this was not associated with altered expression of myosin isoforms or impaired contractile properties of muscles. These increases in fatigue and depressive-like behaviors were paralleled by increased expression of IL-1β mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1β in the brain, reduced depressive-like behavior, and improved grip strength without altering muscle mass. Taken together, these results indicate that neuroinflammation and depressed mood, rather than muscle wasting, contribute to decreased voluntary activity and precede major changes in muscle contractile properties with tumor growth.
authors.affiliation: Department of Neuroscience, The Ohio State University, 333 W. 10th Ave., Columbus, OH 43210, United States.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Norden
authors.affiliation: Division of Biosciences, College of Dentistry, The Ohio State University, 305 W. 12th Ave., Columbus, OH, United States.
authors.forename: Sabahattin
authors.initials: S
authors.lastname: Bicer
authors.affiliation: College of Nursing, The Ohio State University, 1585 Neil Ave., Columbus, OH, United States.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Clark
authors.affiliation: College of Nursing, The Ohio State University, 1585 Neil Ave., Columbus, OH, United States.
authors.forename: Runfeng
authors.initials: R
authors.lastname: Jing
authors.affiliation: Department of Neuroscience, The Ohio State University, 333 W. 10th Ave., Columbus, OH 43210, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Henry
authors.affiliation: College of Nursing, The Ohio State University, 1585 Neil Ave., Columbus, OH, United States; Department of Physiology and Cell Biology, The Ohio State University, 370 W. 9th Ave., Columbus, OH, United States.
authors.forename: Loren E
authors.initials: LE
authors.lastname: Wold
authors.affiliation: Division of Biosciences, College of Dentistry, The Ohio State University, 305 W. 12th Ave., Columbus, OH, United States.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Reiser
authors.affiliation: Department of Neuroscience, The Ohio State University, 333 W. 10th Ave., Columbus, OH 43210, United States; Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Dr., Columbus, OH, United States.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Godbout
authors.affiliation: College of Nursing, The Ohio State University, 1585 Neil Ave., Columbus, OH, United States. Electronic address: donnalee.mccarthy@mu.edu.
authors.forename: Donna O
authors.initials: DO
authors.lastname: McCarthy
mesh_terms: D000230:Adenocarcinoma / Q000150:complications* / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003110:Colonic Neoplasms / Q000150:complications* / Q000503:physiopathology; D003863:Depression / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005221:Fatigue / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D051379:Mice; D009043:Motor Activity / Q000502:physiology*; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009368:Neoplasm Transplantation; D011788:Quality of Life
keywords: Cancer; Cytokines; Depression; Fatigue; Minocycline; Neuroinflammation
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