Voluntary wheel running ameliorates select paclitaxel chemotherapy-induced sickness behaviors and associated melanocortin signaling.
Animals
Antineoplastic Agents
/ adverse effects
Behavior, Animal
/ drug effects
Cachexia
/ chemically induced
Cytokines
/ blood
Fatigue
/ chemically induced
Female
Fever
/ chemically induced
Ghrelin
/ blood
Illness Behavior
/ drug effects
Inflammation
/ chemically induced
Leptin
/ blood
Melanocortins
/ metabolism
Mice, Inbred C57BL
Motor Activity
/ drug effects
Paclitaxel
/ adverse effects
Physical Conditioning, Animal
/ physiology
Signal Transduction
/ physiology
Antineoplastic
Cytokines
Exercise
Ghrelin
Leptin
Neuroinflammation
Journal
Behavioural brain research
ISSN: 1872-7549
Titre abrégé: Behav Brain Res
Pays: Netherlands
ID NLM: 8004872
Informations de publication
Date de publication:
05 02 2021
05 02 2021
Historique:
received:
28
08
2020
revised:
30
10
2020
accepted:
30
11
2020
pubmed:
7
12
2020
medline:
16
11
2021
entrez:
6
12
2020
Statut:
ppublish
Résumé
While chemotherapy remains a common cancer treatment, it is associated with debilitating side effects (e.g., anorexia, weight loss, and fatigue) that adversely affect patient quality of life and increase mortality. However, the mechanisms underlying taxane chemotherapy-induced side effects, and effective treatments to ameliorate them, are not well-established. Here, we tested the longitudinal relationship between a clinically-relevant paclitaxel regimen, inflammation, and sickness behaviors (loss of body mass, anorexia, fever, and fatigue) in adult, female mice. Furthermore, we sought to identify the extent to which voluntary exercise (wheel running) attenuates paclitaxel-induced sickness behaviors and underlying central pathways. Body mass and food intake decreased following six doses of chemotherapy treatment relative to vehicle controls, lasting less than 5 days after the last dose. Paclitaxel treatment also transiently decreased locomotion (open field test), voluntary wheel running, home-cage locomotion, and core body temperature without affecting motor coordination (rotarod task). Circulating interleukin (IL)-6 and hypothalamic Il1b gene expression remained elevated in chemotherapy-treated mice at least 3 days after the last dose. Exercise intervention did not ameliorate fatigue or inflammation, but hastened recovery from paclitaxel-induced weight loss. Body mass recovery was associated with the wheel running-induced recovery of body composition, paclitaxel-induced alterations to hypothalamic melanocortin signaling, and associated peripheral circulating hormones (ghrelin and leptin). The present findings demonstrate the benefits of exercise on faster recovery from paclitaxel-induced body mass loss and deficits in melanocortin signaling and suggests the development of therapies targeting the melanocortin pathway to reduce paclitaxel-induced weight loss.
Identifiants
pubmed: 33279635
pii: S0166-4328(20)30740-3
doi: 10.1016/j.bbr.2020.113041
pmc: PMC7856259
mid: NIHMS1653987
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Cytokines
0
Ghrelin
0
Leptin
0
Melanocortins
0
Paclitaxel
P88XT4IS4D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113041Subventions
Organisme : NCI NIH HHS
ID : R01 CA216290
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
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