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Optimal locations and parameters of gastric electrical stimulation in altering ghrelin and oxytocin in the hypothalamus of rats
Institution:1. Division of Mass Spectrometry, Korea Basic Science Institute, Ochang-Myun, Cheongwon-Gun 363-883, Republic of Korea;2. Department of Chemistry, Hannam University, Daejeon 306-791, Republic of Korea;3. Targeted Gene Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea;4. Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea;5. GRAST, Chungnam National University, Daejeon 305-764, Republic of Korea;1. Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain;2. Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain;3. Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón, I+CS, Zaragoza, Spain;4. Hospital Universitario Miguel Servet, Servicio de Cardiología, Zaragoza, Spain;1. Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK;2. Department of Cellular and Molecular Physiology, University of Liverpool, Nuffield Building, Liverpool L69 3BX, UK;3. Department of Obesity and Endocrinology, Clinical Sciences Center, University Hospital Anitree, Liverpool L9 7AL, UK;4. Center for Genetic Medicine Research, Children''s National Medical Center, Washington, DC 20010, USA;5. Department of Mathematics and Statistics, Liverpool John Moores University, Liverpool L3 3AF, UK;6. Department of Integrative Systems Biology, George Washington University, Washington DC, USA;7. Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park IC2, L3 5RF, UK;8. Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-2200, USA;9. Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109-2200, USA
Abstract:Gastric electric stimulation (GES) has been shown to decrease gastric tone and antrum motility, delay gastric empty, suppress appetite and induce weight loss in animal models. Our previous studies have shown that GES activates gastric-distension responsive neurons in several satiety related hypothalamic nuclei; Two hour acute GES at gastric antrum can alter the expression of anorexigenic and orexigenic peptides in the hypothalamus of rats.AimTo investigate the effects of GES with different stimulation parameters and locations on the neuronal expression of a hunger hormone, ghrelin and a satiety hormone, oxytocin (OT) in the hypothalamus of rats.MethodsWith immunohistochemical technique, changes in expression of satiety-related peptides-containing (OT- and ghrelin-) neurons with GES in the rodent hypothalamus were assessed. GES was performed for 2 h using six different sets of parameters at three different locations.Results(1) The number of ghrelin/OT-immunoreactive (IR) neurons was significantly decreased/increased with GES of the standard parameters (pulse trains: train on-time of 2 s, off-time of 3 s, pulse amplitude of 6 mA, width of 0.3 ms and frequency of 40 Hz) in both the paraventricular nucleus (PVN) and the superoptical nucleus (SON) compared with the control group, but not with GES of reduced pulse amplitudes, frequencies or train-on times. (2) GES with the standard parameters at the antrum resulted in a significant decrease/increase in the expression of ghrelin/OT in the PVN and the SON. However, GES at other locations (middle of lesser curvature or greater curvature) was not effective in altering the expression of ghrelin/OT.ConclusionsGES with the standard parameters delivered at the distal antrum increases/decreases oxytocin/ghrelin in the hypothalamus of rats. GES with reduced parameters or delivered at the middle of the stomach is ineffective in altering these peptides.
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