Evaluation of the effects of chemotherapy-induced fatigue and pharmacological interventions in multiple mouse behavioral assays

Dougherty, John P.; Springer, Danielle; Cullen, Mary Jane; Gershengorn, Marvin C.

doi:10.1016/j.bbr.2018.12.011

Cited by 13 publications

(7 citation statements)

References 44 publications

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“…We did not see differences in open field behavior in mice treated with 5FU, which matches prior studies using 5FU ( Dougherty et al, 2019 ) or doxycycline ( Zombeck et al, 2013 ). However, prior studies comparing Val66Met mice to WT have found an anxiety-like phenotype ( Chen et al, 2006 ; Bath et al, 2012a ) that we did not see.…”

Section: Discussionsupporting

confidence: 91%

“…We speculate that fatigue-like outcomes in mice may have a substantial dependence on mouse substrain, much like what we saw in a previous study with a radiation-induced fatigue model, where C57BL/6J mice showed considerably less fatigue-like behavior than C57BL/6N mice ( Wolff et al, 2021 ). Further supporting this is a study by Dougherty et al (2019) that used the same dosing paradigm as Mahoney et al (2013) with C57BL/6N mice, but Dougherty et al (2019) saw a much more severe fatigue-like behavior with a nearly complete cessation of VWRA.…”

Section: Discussionmentioning

confidence: 88%

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BDNF Val66Met Polymorphism Reduces the Fatigue-Like Effects of 5-Fluorouracil on Voluntary Wheel-Running Activity in Mice

Wolff

Allen

Feng

et al. 2022

Front. Behav. Neurosci.

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Fatigue is a persistent and debilitating symptom following cancer treatments such as chemotherapy. Recent clinical studies have suggested a common single-nucleotide polymorphism of brain-derived neurotrophic factor (BDNF), Val66Met (rs6265), may be related to the severity of fatigue following cancer treatment. In this study, we tested transgenic mice homozygous for the human Val66Met BDNF gene and wild-type controls. We injected three doses of 5-fluorouracil (5FU) as a model of chemotherapy treatment, and we used changes in voluntary wheel running activity (VWRA) as a measure of fatigue-like behavior. Prior to 5FU injection, we found that during the baseline wheel-running period, the Val66Met mice lost more weight than WT controls. We next administered 5FU and saw a robust fatigue-like phenotype that lasted about 2 weeks. During the first week, the fatigue-like phenotype was less severe in the Val66Met mice and unrelated to the age of the mice. In contrast, during the second week after 5FU treatment, the fatigue-like phenotype was unrelated to the BDNF genotype but was more severe in middle aged mice compared to young mice. We conclude that the BDNF polymorphism may play a direct, protective role against chemotherapy-induced fatigue.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 88%

BDNF Val66Met Polymorphism Reduces the Fatigue-Like Effects of 5-Fluorouracil on Voluntary Wheel-Running Activity in Mice

Wolff

Allen

Feng

et al. 2022

Front. Behav. Neurosci.

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“…There is yet little data available on long-term effects of either chemo- or radiotherapy on frailty in mice. Available mouse models of radiation- or chemotherapy-induced fatigue cover only some aspects of frailty and importantly are generally only evaluated over short periods, covering essentially only the period of acute radio- or chemotoxicity (Demaria et al, 2017; Dougherty et al, 2019; Renner et al, 2016; Wolff et al, 2017). In one paper, running wheel activity after localized irradiation (single leg) has been shown to be compromised for up to seven months (Zhu et al, 2015), but further domains of frailty were not assessed.…”

Section: Introductionmentioning

confidence: 99%

Sublethal whole-body irradiation causes progressive premature frailty in mice

Fielder

Weigand

Agneessens

et al. 2019

Mechanisms of Ageing and Development

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Highlights Mice that survive irradiation develop progressive frailty. Irradiation-induced premature frailty is phenotypically equal to frailty in old animals. Premature frailty is associated with mortality and low cognition. Sub-lethal whole body irradiation may constitute a good mouse model to test efficiency of anti-ageing interventions.

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“…We observed that 5-FU administered at 60 mg/kg caused mortality in the placebo (11.5%) and vitamin C (16%) groups, a percentage likely reduced (4%) but not statistically relevant in the Qiseng ® group. The 60 mg/kg dose was optimal to induce intestinal mucositis in mice [ 73 ] without reporting mortality [ 74 , 75 ]. It can be hypothesized that the cytotoxic effect of chemotherapy, combined with the stress induced by handling, i.p.…”

Section: Discussionmentioning

confidence: 99%

A Panax quinquefolius-Based Preparation Prevents the Impact of 5-FU on Activity/Exploration Behaviors and Not on Cognitive Functions Mitigating Gut Microbiota and Inflammation in Mice

Parment

Dubois

Desrues

et al. 2022

Cancers

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Chemotherapy-related cognitive impairment (CRCI) and fatigue constitute common complaints among cancer patient survivors. Panax quinquefolius has been shown to be effective against fatigue in treated cancer patients. We developed a behavioral C57Bl/6j mouse model to study the role of a Panax quinquefolius-based solution containing vitamin C (Qiseng®) or vitamin C alone in activity/fatigue, emotional reactivity and cognitive functions impacted by 5-Fluorouracil (5-FU) chemotherapy. 5-FU significantly reduces the locomotor/exploration activity potentially associated with fatigue, evokes spatial cognitive impairments and leads to a decreased neurogenesis within the hippocampus (Hp). Qiseng® fully prevents the impact of chemotherapy on activity/fatigue and on neurogenesis, specifically in the ventral Hp. We observed that the chemotherapy treatment induces intestinal damage and inflammation associated with increased levels of Lactobacilli in mouse gut microbiota and increased expression of plasma pro-inflammatory cytokines, notably IL-6 and MCP-1. We demonstrated that Qiseng® prevents the 5-FU-induced increase in Lactobacilli levels and further compensates the 5-FU-induced cytokine release. Concomitantly, in the brains of 5-FU-treated mice, Qiseng® partially attenuates the IL-6 receptor gp130 expression associated with a decreased proliferation of neural stem cells in the Hp. In conclusion, Qiseng® prevents the symptoms of fatigue, reduced chemotherapy-induced neuroinflammation and altered neurogenesis, while regulating the mouse gut microbiota composition, thus protecting against intestinal and systemic inflammation.

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Evaluation of the effects of chemotherapy-induced fatigue and pharmacological interventions in multiple mouse behavioral assays

Cited by 13 publications

References 44 publications

BDNF Val66Met Polymorphism Reduces the Fatigue-Like Effects of 5-Fluorouracil on Voluntary Wheel-Running Activity in Mice

BDNF Val66Met Polymorphism Reduces the Fatigue-Like Effects of 5-Fluorouracil on Voluntary Wheel-Running Activity in Mice

Sublethal whole-body irradiation causes progressive premature frailty in mice

A Panax quinquefolius-Based Preparation Prevents the Impact of 5-FU on Activity/Exploration Behaviors and Not on Cognitive Functions Mitigating Gut Microbiota and Inflammation in Mice

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