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

Norden, Diana M.; Devine, Raymond D.; Bicer, Sabahattin; Jing, Runfeng; Reiser, Peter J.; Wold, Loren E.; Godbout, Jonathan P.; McCarthy, Donna O.

doi:10.1016/j.physbeh.2014.12.045

Cited by 36 publications

(28 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fluoxetine administration reduced depressive-like behaviors in tumor-bearing mice, but did not have an effect on KMO mRNA or IDO expression (Norden et al, 2015). On the other hand, in a BV-2 microglial cell line, fluoxetine alone or in combination with acetylsalicylic acid inhibited microglial activation and attenuated LPS-induced production of IL-1β, expression of IDO, and the depletion of 5-HT (Yang et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

Kynurenine pathway dysfunction in the pathophysiology and treatment of depression: Evidences from animal and human studies

Réus¹,

Jansen

Titus³

et al. 2015

Journal of Psychiatric Research

197

113

View full text Add to dashboard Cite

Treatment-resistant depression affects up to 20% of individuals suffering from major depressive disorder (MDD). The medications currently available to treat depression, including serotonin re-uptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), fail to produce adequate remission of depressive symptoms for a large number of patients. The monoamine hypothesis upon which these medications are predicated should be expanded and revised as research elucidates alternative mechanisms of depression and effective methods to treat the underlying pathologic consequences. Research into the role of tryptophan degradation and the kynurenine pathway in the setting of inflammation has brought new insight into potential etiologies of MDD. Further investigation into the connection between inflammatory mediators, tryptophan degradation, and MDD can provide many targets for novel antidepressant therapies. Thus, this review will highlight the role of the kynurenine pathway in the pathophysiology of depression, as well as a novel therapeutic target to classic and new modulators to treat depression based on findings from preclinical and clinical studies.

show abstract

Section: Resultsmentioning

confidence: 99%

Kynurenine pathway dysfunction in the pathophysiology and treatment of depression: Evidences from animal and human studies

Réus¹,

Jansen

Titus³

et al. 2015

Journal of Psychiatric Research

197

113

View full text Add to dashboard Cite

show abstract

“…Traditionally, the major depression is usually considered a disorder associated with microglial overactivation, and this was evidenced by numerous studies. For example, cytokine therapy has been reported to generate depressive symptoms in cancer patients [30,31]. Administrating LPS and/or pro-inflammatory mediators induces depressive-like behaviors including impairment of sucrose preference and loss of hope to escape from despairing environments [32,33].…”

Section: Discussionmentioning

confidence: 99%

Microglia Loss Contributes to the Development of Major Depression Induced by Different Types of Chronic Stresses

et al. 2017

View full text Add to dashboard Cite

Recently, the loss and dystrophy of hippocampal microglia induced by chronic unpredictable stress (CUS) has been reported to mediate the development of major depression in mice whose microglial cells were labeled with enhanced green fluorescent protein-conjuncted-CX3C receptor type 1. However, whether this happens in endogenous microglia with no genetic intervention remains unclear. Here, we addressed this issue in mice treated with different types of chronic stresses, including the CUS, chronic restraint stress (CRS) and chronic social defeat stress (CSDS). Results showed that the cellular numbers, process lengths, soma areas and activation markers of endogenous hippocampal but not cortical microglia, were markedly reduced by CUS, CRS and CSDS treatment. Administration of mice with two classical stimulators of microglia, lipopolysaccharide (LPS) or macrophage colony-stimulating factor (M-CSF), reversed the CUS-, CRS- and CSDS-induced reductions in endogenous hippocampal microglial numbers, and also improved the CUS-, CRS- or CSDS-induced behavioral abnormalities, including the increases in the immobile time in the forced swimming test and tail suspension test, the inhibition of sucrose preference, and the decrease in the time spent in the center of open field. Furthermore, inhibition of the initial activation of hippocampal microglia by minocycline pretreatment also reversed the reduction in hippocampal microglial numbers as well as the behavioral abnormalities induced by CUS, CRS and CSDS treatment. These results provide compelling evidences to show that different types of chronic stresses can trigger the loss of endogenous hippocampal microglia and restoration of microglial numbers may have therapeutic values in major depression.

show abstract

“…This is critical as we have previously shown that increased inflammation in the brains of tumor-bearing mice is associated with both fatigue-and depressive like behaviors (19). Administration of minocycline, a broad spectrum antibiotic with anti-inflammatory capacity, inhibited microglial activation in tumor-bearing mice which resulted in reduced neuroinflammation and reduced depressive-like behavior in tumor-bearing mice (11).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, increased neuroinflammation is thought to induce depressive-like behavior via increased activity of IDO and KMO, which may reduce serotonin synthesis and availability in the brain (43, 44). For example, we have previously shown that treatment with the SSRI Fluoxetine ameliorated depressive-like behavior in tumor bearing mice (19). Here we show that ibuprofen decreased IL-1β and IL-6 mRNA expression in the hippocampus of tumor-bearing mice to levels seen in healthy control mice.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ibuprofen ameliorates fatigue- and depressive-like behavior in tumor-bearing mice

et al. 2015

Self Cite

View full text Add to dashboard Cite

Aims Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines are associated with skeletal muscle wasting and depressive- and fatigue- like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF. Main Methods Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10mg/kg) in the drinking water. Depressive-like behavior was determined using the forced swim test (FST). Fatigue-like behaviors were determined using voluntary wheel running activity (VWRA) and grip strength. The hippocampus, gastrocnemius muscle, and serum were collected for cytokine analysis. Key Findings Tumor-bearing mice showed depressive-like behavior in the FST, which was not observed in mice treated with ibuprofen. VWRA and grip strength declined in tumor-bearing mice, and ibuprofen attenuated this decline. Tumor-bearing mice had decreased gastrocnemius muscle mass and increased expression of IL-6, MAFBx and MuRF mRNA, biomarkers of protein degradation, in the muscle. Expression of IL-1β and IL-6 was also increased in the hippocampus. Treatment with ibuprofen improved muscle mass and reduced cytokine expression in both the muscle and hippocampus of tumor-bearing mice. Significance Ibuprofen treatment reduced skeletal muscle wasting, inflammation in the brain, and fatigue- and depressive-like behavior in tumor-bearing mice. Therefore, ibuprofen warrants evaluation as an adjuvant treatment for CRF.

show abstract

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

Cited by 36 publications

References 44 publications

Kynurenine pathway dysfunction in the pathophysiology and treatment of depression: Evidences from animal and human studies

Kynurenine pathway dysfunction in the pathophysiology and treatment of depression: Evidences from animal and human studies

Microglia Loss Contributes to the Development of Major Depression Induced by Different Types of Chronic Stresses

Ibuprofen ameliorates fatigue- and depressive-like behavior in tumor-bearing mice

Contact Info

Product

Resources

About