Voluntary wheel running ameliorates select paclitaxel chemotherapy-induced sickness behaviors and associated melanocortin signaling

Sullivan, Kyle A.; Grant, Corena V.; Jordan, Kelley R.; Vickery, S.; Pyter, Leah M.

doi:10.1016/j.bbr.2020.113041

Cited by 12 publications

(15 citation statements)

References 55 publications

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“…Locomotor activity assessment in cancer patients often uses wrist actigraphy and smartwatches to track movement, which is similar to our measurement of movement in the open field test ( 61 – 63 ). The timing of the observed locomotor activity reduction, which occurred shortly after chemotherapy, was consistent with other human and rodent studies ( 7 , 49 , 64 , 65 ). Specifically, paclitaxel (used in this model), induces fatigue in humans and reduces locomotor activity in rodents ( 49 , 65 , 66 ).…”

Section: Discussionsupporting

confidence: 90%

“…The timing of the observed locomotor activity reduction, which occurred shortly after chemotherapy, was consistent with other human and rodent studies ( 7 , 49 , 64 , 65 ). Specifically, paclitaxel (used in this model), induces fatigue in humans and reduces locomotor activity in rodents ( 49 , 65 , 66 ). Of note, our previous work using ovary-intact, tumor-free mice indicates that paclitaxel induces central but not muscle-related reduced locomotor activity ( 49 ).…”

Section: Discussionsupporting

confidence: 90%

“…When mice were allowed to recover from chemotherapy and receive an aromatase inhibitor, these FA and ADC alterations resolved. Specifically, FA and ADC alterations were absent after 1 dose, although previous work indicates that reduced locomotor activity is already detectable at this time ( 49 ), suggesting that FA and ADC may not directly relate to reduced locomotor activity. While DWI was used to specifically assess white matter changes within the brain, broad and diffuse FA and ADC changes were observed after the 6 th dose of paclitaxel, likely indicating widespread inflammation throughout white and gray matter of the brain.…”

Section: Discussionmentioning

confidence: 72%

“…Specifically, paclitaxel (used in this model), induces fatigue in humans and reduces locomotor activity in rodents ( 49 , 65 , 66 ). Of note, our previous work using ovary-intact, tumor-free mice indicates that paclitaxel induces central but not muscle-related reduced locomotor activity ( 49 ). We have also previously demonstrated that tumor resection reduces locomotor activity on its own ( 43 ), indicating that in the present study chemotherapy may exacerbate tumor resection-induced reduced locomotor activity.…”

Section: Discussionmentioning

confidence: 99%

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Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging

et al. 2022

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Breast cancer is one of the most common diseases in the United States with 1 in 8 women developing the disease in her lifetime. Women who develop breast cancer are often post-menopausal and undergo a complex sequence of treatments including surgery, chemotherapy, and aromatase inhibitor therapy. Both independently and through potential interactions, these factors and treatments are associated with behavioral comorbidities reported in patients (e.g., fatigue), although the underlying neurobiological mechanisms are poorly understood. Currently, brain imaging is the most feasible way to assess neurobiology in patients. Indeed, breast cancer patients display alterations in white matter connections and chemotherapy is associated with decreased white and gray matter in the corpus callosum and cortex as well as decreased hippocampal volume. However, imaging in breast cancer rodent models is lacking, impeding translation of the mechanistic neurobiological findings made possible through modeling. Furthermore, current rodent models of breast cancer often lack the complexity of typical multimodal breast cancer treatments, thereby limiting translational value. The present study aimed to develop a comprehensive model of post-menopausal breast cancer survival using immunocompetent ovariectomized mice, including an orthotopic syngeneic tumor, surgical tumor removal, chemotherapy, and aromatase inhibitor therapy. Using this model, we systematically investigated the cumulative effects of chemotherapy and hormone replacement therapy on neurostructure and behavior using diffusion weighted imaging, open field test, and spontaneous alternation test. Our previous findings, in a simplified chemotherapy-only model, indicate that this regimen of chemotherapy causes circulating and central inflammation concurrent with reduced locomotor activity. The current study, in the more comprehensive model, has recapitulated the peripheral inflammation coincident with reduced locomotor activity as well as demonstrated that chemotherapy also drives widespread changes in brain anisotropy. Validating the clinical relevance of this comprehensive rodent breast cancer model will allow for additional neurobiological investigations of the interactions among various cancer components associated with behavioral comorbidities, as well as the relationship between these mechanisms and neurostructural imaging changes that can be measured in cancer patients.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

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Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging

et al. 2022

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“…10. One of the important aspects of paclitaxelinduced neuropathy is the disturbance in latency of falling [40], body weight [41], and mechanical allodynia [42]. The behavioral analysis of our compounds reveals that berbamine, bergepten and carveol are corrected the behavioral de cit in paclitaxel-induced peripheral neuropathic pain as is shown in Fig.…”

Section: Discussionmentioning

confidence: 56%

Neuroprotective Effects of Berbamine, Bergepten, and Carveol on Paclitaxel-Induced Peripheral Neuropathy

Faheem

Khan

Ijaz³

et al. 2022

Preprint

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Background: The current study investigates the effects of natural chemicals like berbamine (BBR), bergepten (BRG), and carveol (CAR) on paclitaxel (PTX) associated neuro-inflammatory pain. Methods: The induction was carried out by administering 2 mg/kg PTX for a week with a day gap. On 7th, 14th and 21st days, behavioral testing was executed, and tissue was removed for molecular analysis. Results: Treatment attenuates thermal hyperalgesia, improved latency of falling, normalized the changes in body weight and increased threshold for pain sensation. The drugs increased the protective GSH and GST levels in the sciatic nerve and spinal cord, while lowering iNOS and LPO. H and E and IHC examinations confirmed that the medication reversed the abnormal alterations. Conclusion: The aforementioned natural substances inhibit COX-2, TNF-α and NF-κB over-expression, as evidenced by enzyme-linked immunosorbent assay (Elisa) and western blot, and hence provide neuroprotection in chronic constriction damage.

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Manipulations of the gut microbiome alter chemotherapy-induced inflammation and behavioral side effects in female mice

Grant¹,

Loman²,

Bailey³

et al. 2021

Brain, Behavior, and Immunity

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Voluntary wheel running ameliorates select paclitaxel chemotherapy-induced sickness behaviors and associated melanocortin signaling

Cited by 12 publications

References 55 publications

Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging

Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging

Neuroprotective Effects of Berbamine, Bergepten, and Carveol on Paclitaxel-Induced Peripheral Neuropathy

Manipulations of the gut microbiome alter chemotherapy-induced inflammation and behavioral side effects in female mice

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