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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-1? mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1? 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.

SUBMITTER: Norden DM

PROVIDER: S-EPMC4258420 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Tumor growth increases neuroinflammation, fatigue and depressive-like behavior prior to alterations in muscle function.

Norden Diana M DM Bicer Sabahattin S Clark Yvonne Y Jing Runfeng R Henry Christopher J CJ Wold Loren E LE Reiser Peter J PJ Godbout Jonathan P JP McCarthy Donna O DO

Brain, behavior, and immunity 20140804

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 ...[more]

PMID: 25102452

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Project description:The oxygen-conforming response (OCR) of skeletal muscle refers to a downregulation of muscle force for a given muscle activation when oxygen delivery (O2D) is reduced, which is rapidly reversed when O2D is restored. We tested the hypothesis that the OCR exists in voluntary human exercise and results in compensatory changes in muscle activation to maintain force output, thereby altering perception of effort. In eight men and eight women, electromyography (EMG), oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb), forearm blood flow (FBF), and task effort awareness (TEA) were measured. Participants completed two nonfatiguing rhythmic handgrip tests consisting of 5-min steady state (SS) followed by two bouts of 2-min brachial artery compression to reduce FBF by ~50% of SS (C1 and C2), separated by 2 min of no compression (NC1) and ending with 2 min of no compression (NC2). When FBF was compromised during C1, EMG/Force (1.58?±?0.39) increased compared with SS (1.31?±?0.33, P = 0.001). However, EMG/Force was not restored upon FBF restoration at NC1 (1.48?±?0.38, P = 0.479), consistent with C1 evoking skeletal muscle fatigue. When FBF was compromised during C2, EMG/Force increased (1.73?±?0.50) compared with NC1 (1.48?±?0.38, P = 0.013). EMG/Force returned to NC1 levels during NC2 (1.50?±?0.39, P = 0.016), consistent with an OCR in C2. TEA (SS 2.2?±?2.3, C1 3.9?±?2.5, NC1 3.4?±?2.7, C2 4.6?±?2.7, NC2 3.9?±?2.8) mirrored changes in EMG. It is noteworthy that during the second compromise and then restoration of muscle oxygenation EMG and TEA were rapidly restored to precompromise levels. We interpreted these findings to support the existence of an OCR and its ability to rapidly modify perception of effort during voluntary exercise. NEW & NOTEWORTHY In healthy individuals, when force output is maintained during rhythmic handgrip exercise, muscle activation and perception of effort rapidly increase with compromised muscle oxygen delivery (O2D) and then return to precompromised levels when muscle O2D is restored. These findings suggest that an oxygen-conforming response (OCR) exists and is able to modify perception of effort during voluntary exercise. Therefore, similar to fatigue, an OCR may have implications for exercise tolerance.

Dataset Information

Tumor growth increases neuroinflammation, fatigue and depressive-like behavior prior to alterations in muscle function.

Publications

Tumor growth increases neuroinflammation, fatigue and depressive-like behavior prior to alterations in muscle function.

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