Cytotoxic chemotherapy increases sleep and sleep fragmentation in non-tumor-bearing mice

Borniger, J. C., Gaudier-Diaz, M. M., Zhang, N., Nelson, R. J., DeVries, A. C. (July 2015) Cytotoxic chemotherapy increases sleep and sleep fragmentation in non-tumor-bearing mice. Brain Behav Immun, 47. pp. 218-27. ISSN 1090-2139 (Electronic)0889-1591 (Linking)

DOI: 10.1016/j.bbi.2014.11.001


Sleep disruption ranks among the most common complaints of breast cancer patients undergoing chemotherapy. Because of the complex interactions among cancer, treatment regimens, and life-history traits, studies to establish a causal link between chemotherapy and sleep disruption are uncommon. To investigate how chemotherapy acutely influences sleep, adult female c57bl/6 mice were ovariectomized and implanted with wireless biotelemetry units. EEG/EMG biopotentials were collected over the course of 3days pre- and post-injection of 13.5mg/kg doxorubicin and 135mg/kg cyclophosphamide or the vehicle. We predicted that cyclophosphamide+doxorubicin would disrupt sleep and increase central proinflammatory cytokine expression in brain areas that govern vigilance states (i.e., hypothalamus and brainstem). The results largely support these predictions; a single chemotherapy injection increased NREM and REM sleep during subsequent active (dark) phases; this induced sleep was fragmented and of low quality. Mice displayed marked increases in low theta (5-7Hz) to high theta (7-10Hz) ratios following chemotherapy treatment, indicating elevated sleep propensity. The effect was strongest during the first dark phase following injection, but mice displayed disrupted sleep for the entire 3-day duration of post-injection sleep recording. Vigilance state timing was not influenced by treatment, suggesting that acute chemotherapy administration alters sleep homeostasis without altering sleep timing. qPCR analysis revealed that disrupted sleep was accompanied by increased IL-6 mRNA expression in the hypothalamus. Together, these data implicate neuroinflammation as a potential contributor to sleep disruption after chemotherapy.

Item Type: Paper
Subjects: Investigative techniques and equipment > cloning > PCR
Investigative techniques and equipment > assays > cloning > PCR
organism description > animal behavior > REM sleep
diseases & disorders > cancer > drugs and therapies > chemotherapy
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL labs > Borniger lab
Depositing User: Adrian Gomez
Date: July 2015
Date Deposited: 03 Jan 2020 17:55
Last Modified: 03 Jan 2020 17:55
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