Hippocampal dysfunctions in tumor-bearing mice

Yang, Miyoung; Kim, Juhwan; Kim, Joong Sun; Kim, Sung Hoon; Kim, Jong Choon; Kang, Man‐Jong; Jung, Uhee; Shin, Taekyun; Wang, Hongbing; Moon, Changjong

doi:10.1016/j.bbi.2013.10.022

Cited by 78 publications

(72 citation statements)

References 64 publications

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“…In support of this idea, tumor-bearing mice showed reduced sucrose preference at one and two weeks after tumor cell inoculation, and increased time immobile in the FST at the two week time point. Other studies have shown that peripheral tumors induce depressive-like behavior concurrent with reduced body mass in rodents (Lamkin et al, 2011; Pyter et al, 2009; Yang et al, 2014). Our study, however, shows that depressive-like behavior occurs early in the course of tumor growth and precedes tumor induced weight loss or muscle wasting.…”

Section: Discussionmentioning

confidence: 93%

“…Female mice were used because we and others have shown that tumor-bearing females maintain their food intake and lose a smaller percent of body mass than male mice (Cosper and Leinwand, 2011) and male mice often gnaw and bite at the tumor site (Yang et al, 2014). Mice were housed 1–3 per cage and maintained at 25°C under a 12 h light cycle with ad libitum access to water and rodent chow.…”

Section: Methodsmentioning

confidence: 99%

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

Norden

Bicer

Clark

et al. 2015

Brain, Behavior, and Immunity

107

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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.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

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

Norden

Bicer

Clark

et al. 2015

Brain, Behavior, and Immunity

107

View full text Add to dashboard Cite

show abstract

“…Female mice were used because we and others have shown that tumor-bearing females maintain their food intake longer and lose a smaller percent of body mass than male mice [22] and male mice tend to gnaw and bite at the tumor site more than females, causing local inflammation [23]. Mice were singly housed and maintained at 25°C under a 12 h light cycle with ad libitum access to water and rodent chow.…”

Section: Methodsmentioning

confidence: 99%

Fluoxetine prevents the development of depressive-like behavior in a mouse model of cancer related fatigue

Norden

Devine

Bicer

et al. 2015

Physiology & Behavior

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Cancer patients frequently suffer from fatigue, a complex syndrome associated with tiredness and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, escalates during treatment, and can persist for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. We have previously shown that increased pro-inflammatory cytokine expression in the brain contributes to depressive- and fatigue- like behaviors in a mouse model of CRF. Inflammatory cytokines increase activity of indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO), which competitively reduce serotonin synthesis. Reduced serotonin availability in the brain and increased production of alternative neuroactive metabolites of tryptophan are thought to contribute to the development of depression and fatigue. The purpose of this study was to determine the effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on brain cytokines and behavioral measures of fatigue and depression in tumor-bearing mice. Here we show that tumor growth increased brain expression of pro-inflammatory cytokines and KMO. Treatment with fluoxetine had no effect on tumor growth, muscle wasting, fatigue behavior, or cytokine expression in the brain. Fluoxetine, however, reduced depressive-like behaviors in tumor bearing mice. In conclusion, our data confirm that increased brain expression of pro-inflammatory cytokines is associated with tumor-induced fatigue and depressive-like behavior. However, it is possible to separate the effects of tumor growth on mood and fatigue-like behaviors using SSRI’s such as fluoxetine.

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“…The immunohistochemical methodology has been described in detail previously (Kim et al, 2008;Yang et al, 2012;Yang et al, 2014). Briefly, sagittal sections (4 m thick) were deparaffinized and hydrated, blocked in a 5% (v/v) solution of NGS (Vector ABC Elite Kit) in PBS-T, reacted with rabbit anti-DCX in antibody diluent (Invitrogen) overnight at 4 • C, and next incubated with biotinylated goat anti-rabbit IgG (Vector ABC Elite Kit) for 1 h at RT.…”

Section: Immunohistochemistry Of Paraffin-embedded Sectionsmentioning

confidence: 99%

Nestin expression and glial response in the hippocampus of mice after trimethyltin treatment

et al. 2014

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Hippocampal dysfunctions in tumor-bearing mice

Cited by 78 publications

References 64 publications

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

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

Fluoxetine prevents the development of depressive-like behavior in a mouse model of cancer related fatigue

Nestin expression and glial response in the hippocampus of mice after trimethyltin treatment

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