Sleep pattern and locomotor activity are impaired by doxorubicin in non-tumor-bearing rats

Lira, Fábio Santos; Esteves, Andrea Maculano; Pimentel, Gustavo D.; Rosa, José César; Frank, Miriam Kannebley; Mariano, Melise Oliveira; Budni, Josiane; Quevedo, Joao L De; Santos, R; Mello, Marco Túlio de

doi:10.1016/j.slsci.2016.10.006

Cited by 11 publications

(10 citation statements)

References 35 publications

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“…The treatment groups receiving Dox displayed less total movement than those without Dox treatment. This finding is consistent with prior studies of others [ 79 , 80 ] that conceivably could be due to protein oxidation of muscles and/ or the effects of elevated levels of the pro-inflamatory cytokine TNF-α [ 81 , 82 ]. Dox-induced motor dysfunction is not ameliorated by MESNA treatment.…”

Section: Discussionsupporting

confidence: 93%

Doxorubicin-induced elevated oxidative stress and neurochemical alterations in brain and cognitive decline: protection by MESNA and insights into mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”)

et al. 2018

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Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a real and too common complication of cancer chemotherapy experienced by an ever-growing number of cancer survivors. Previously, we reported that doxorubicin (Dox), a prototypical reactive oxygen species (ROS)-producing anti-cancer drug, results in oxidation of plasma proteins, including apolipoprotein A-I (ApoA-I) leading to tumor necrosis factor-alpha (TNF-α)-mediated oxidative stress in plasma and brain. We also reported that co-administration of the antioxidant drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein oxidation and subsequent TNF-α elevation in plasma. In this study, we measured oxidative stress in both brain and plasma of Dox-treated mice both with and without MESNA. MESNA ameliorated Dox-induced oxidative protein damage in plasma, confirming our prior studies, and in a new finding led to decreased oxidative stress in brain. This study also provides further functional and biochemical evidence of the mechanisms of CICI. Using novel object recognition (NOR), we demonstrated the Dox administration resulted in memory deficits, an effect that was rescued by MESNA. Using hydrogen magnetic resonance imaging spectroscopy (H1-MRS) techniques, we demonstrated that Dox administration led to a dramatic decrease in choline-containing compounds assessed by (Cho)/creatine ratios in the hippocampus in mice. To better elucidate a potential mechanism for this MRS observation, we tested the activities of the phospholipase enzymes known to act on phosphatidylcholine (PtdCho), a key component of phospholipid membranes and a source of choline for the neurotransmitter, acetylcholine (ACh). The activities of both phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D were severely diminished following Dox administration. The activity of PC-PLC was preserved when MESNA was co-administered with Dox; however, PLD activity was not protected. This study is the first to demonstrate the protective effects of MESNA on Dox-related protein oxidation, cognitive decline, phosphocholine (PCho) levels, and PC-PLC activity in brain and suggests novel potential therapeutic targets and strategies to mitigate CICI.

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Section: Discussionsupporting

confidence: 93%

Doxorubicin-induced elevated oxidative stress and neurochemical alterations in brain and cognitive decline: protection by MESNA and insights into mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”)

et al. 2018

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“…This decrease in the locomotor activity after irradiation was related to the rapid activation of the neuroimmune system leading to an increased expression of proinflammatory tumor necrosis factor (TNF) in the hippocampus followed by an increase in interleukin‐1 receptor antagonist (IL‐1RA) in the cortex and hippocampus and a reduction in activity‐regulated cytoskeleton‐associated protein (Arc) in the cortex. Activation of the immune system with increased release of cytokines from the central and peripheral tissues induces the sleep disruption and the fatigue symptoms in mice 44,45 …”

Section: Discussionmentioning

confidence: 99%

“…Activation of the immune system with increased release of cytokines from the central and peripheral tissues induces the sleep disruption and the fatigue symptoms in mice. 44,45 Radiotherapy is the common cause of the HPA axis dysfunctions in cancer patients. 46,47 The additional stress induced by radiotherapy further heats up the proinflammatory response leading to a vicious circle.…”

Section: F I G U R Ementioning

confidence: 99%

Relationship between locomotor activity rhythm and corticosterone levels during HCC development, progression, and treatment in a mouse model

Hassan

Ali

Yassine

et al. 2021

Journal of Pineal Research

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“…Researchers working on anxiety in rats/small animals can also benefit from the methods described this survey because with a suitable gesture tracking/pose estimation method, they can quantify rats/animals behavior efficiently and understand how it alters with anxiety [130,131,132,133]. Research on the effects of drugs and cancer on locomotion can also benefit from the methods described in this survey as gesture tracking/pose estimation can be used to understand the changes in locomotion patterns of rats/animals in response to tumors and drugs [134,135,136,137,138,139,140,141,142]. Another field which can benefit from automated gesture analysis is the research on understanding how neural activity controls physical activity or how the brain responds to external stimuli [143,144,145,146,147].…”

Section: Applicationsmentioning

confidence: 99%

“…Research on the effects of drugs and cancer on locomotion can also benefit from the methods described in this survey as gesture tracking/pose estimation can be used to understand the changes in locomotion patterns of rats/animals in response to tumors and drugs [134,135,136,137,138,139,140,141,142].…”

Section: Applicationsmentioning

confidence: 99%

Computer Methods for Automatic Locomotion and Gesture Tracking in Mice and Small Animals for Neuroscience Applications: A Survey

Abbas

Rodó

2019

Sensors

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Neuroscience has traditionally relied on manually observing laboratory animals in controlled environments. Researchers usually record animals behaving freely or in a restrained manner and then annotate the data manually. The manual annotation is not desirable for three reasons; (i) it is time-consuming, (ii) it is prone to human errors, and (iii) no two human annotators will 100% agree on annotation, therefore, it is not reproducible. Consequently, automated annotation for such data has gained traction because it is efficient and replicable. Usually, the automatic annotation of neuroscience data relies on computer vision and machine learning techniques. In this article, we have covered most of the approaches taken by researchers for locomotion and gesture tracking of specific laboratory animals, i.e. rodents. We have divided these papers into categories based upon the hardware they use and the software approach they take. We have also summarized their strengths and weaknesses.

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Sleep pattern and locomotor activity are impaired by doxorubicin in non-tumor-bearing rats

Cited by 11 publications

References 35 publications

Doxorubicin-induced elevated oxidative stress and neurochemical alterations in brain and cognitive decline: protection by MESNA and insights into mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”)

Doxorubicin-induced elevated oxidative stress and neurochemical alterations in brain and cognitive decline: protection by MESNA and insights into mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”)

Relationship between locomotor activity rhythm and corticosterone levels during HCC development, progression, and treatment in a mouse model

Computer Methods for Automatic Locomotion and Gesture Tracking in Mice and Small Animals for Neuroscience Applications: A Survey

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