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Intracerebroventricular injection of ghrelin decreases wheel running activity in rats
Institution:1. Department of Pediatric Surgery, Faculty of Medicine, Kagawa University, Ikenobe, Mikicho, Kitagun, Kagawa, Japan;2. Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Ikenobe, Mikicho, Kitagun, Kagawa, Japan;3. Department of Molecular Microbiology, Faculty of Medicine, Kagawa University, Ikenobe, Mikicho, Kitagun, Kagawa, Japan;4. Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Sakuragaoka, Kagoshima City, Japan;5. Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University, Ikenobe, Mikicho, Kitagun, Kagawa, Japan;1. Department of Integrative Physiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan;2. Student Lab, Faculty of Medicine, Tokushima University, Tokushima 770-8503, Japan;3. PRESTO, JST, Kawaguchi 332-0012, Japan;4. These authors contributed equally
Abstract:There is an increasing interest in elucidating the molecular mechanisms by which voluntary exercise is regulated. In this study, we examined how the central nervous system regulates exercise. We used SPORTS rats, which were established in our laboratory as a highly voluntary murine exercise model. SPORTS rats showed lower levels of serum ghrelin compared with those of the parental line of Wistar rats. Intracerebroventricular and intraperitoneal injection of ghrelin decreased wheel-running activity in SPORTS rats. In addition, daily injection of the ghrelin inhibitor JMV3002 into the lateral ventricles of Wistar rats increased wheel-running activity. Co-administration of obestatin inhibited ghrelin-induced increases in food intake but did not inhibit ghrelin-induced suppression of voluntary exercise in rats. Growth hormone secretagogue receptor (GHSR) in the hypothalamus and hippocampus of SPORTS rats was not difference that in control rats. We created an arcuate nucleus destruction model by administering monosodium glutamate (MSG) to neonatal SPORTS rats. Injection of ghrelin into MSG-treated rats decreased voluntary exercise but did not increase food intake, suggesting that wheel-running activity is not controlled by the arcuate nucleus neurons that regulate feeding. These results provide new insights into the mechanism by which ghrelin regulates voluntary activity independent of arcuate nucleus neurons.
Keywords:Ghrelin  Voluntary exercise  Central nervous system
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