title: Exercise prevents raphe nucleus mitochondrial overactivity in a rat depression model.
abstract: Monoamine deficit and mitochondrial dysfunction may underlie depression. Serotoninergic neurons from raphe nuclei project widely and may be involved in depression. This study used chronic unpredictable stress (CUS) in rats as a model of depression to assess the effects of CUS, exercise and fluoxetine on mitochondrial function and serotonin levels in the raphe nuclei. Rats were divided into 4 groups (6 per group): control (C); depression (D), CUS for 28days; depression+exercise (DE), treadmill exercises from days 11-28 of CUS; depression+fluoxetine (DF), fluoxetine (5mg/kg/d i.g.) from days 11 to 28 of CUS. Behavioral changes were assessed using body weight, sucrose consumption tests (anhedonia) and open field tests (locomotor/exploratory behavior). Raphe nucleus mitochondrial function was determined using the respiratory control ratio, ATP synthesis rate, and activities of superoxide dismutase and glutathione peroxidase. Serotonin levels were measured in the raphe nuclei and hippocampus. On day 28 of CUS, body weight was higher in group C than in groups D, DE and DF (P<0.001), and higher in group DE than in group D or DF (P<0.05). Sucrose consumption was higher in group C than in groups D, DE and DF (P<0.001), higher in group DE than in groups D (P<0.001) or DF (P<0.05), and higher in group DF than in group D (P<0.05). All measures of mitochondrial function were increased in group D compared with the other groups (P<0.01). Hippocampal serotonin was lower in group D than in the other groups (P<0.01); levels in the raphe nuclei were elevated in group DE compared with the remaining groups (P<0.001). CUS in rats may cause overactivation of the mitochondria in the raphe nuclei, and exercise training may suppress these changes.
authors.affiliation: Tianjin Key Laboratory of Exercise Physical & Sport Medicine, Tianjin University of Sport, Tianjin 300381, PR China. Electronic address: wenli34@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.affiliation: Sport Administration Key Laboratory of Sports Psychological and Physiological Regulation, Tianjin University of Sport, Tianjin 300381, PR China.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Sport Administration Key Laboratory of Sports Psychological and Physiological Regulation, Tianjin University of Sport, Tianjin 300381, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Exercise Physical & Sport Medicine, Tianjin University of Sport, Tianjin 300381, PR China.
authors.forename: Shuangyu
authors.initials: S
authors.lastname: Sun
authors.affiliation: Institute of Traumatic Brain Injury and Neurology of Chinese Armed Police Forces, Center for Neurology and Neurosurgery of Logistics College of Chinese Armed Police Forces, Tianjin, PR China.
authors.forename: Shixiang
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Institute of Traumatic Brain Injury and Neurology of Chinese Armed Police Forces, Center for Neurology and Neurosurgery of Logistics College of Chinese Armed Police Forces, Tianjin, PR China.
authors.forename: Sai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Exercise Physical & Sport Medicine, Tianjin University of Sport, Tianjin 300381, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Translational Neuropharmacology, Department of Clinical Neuroscience, Karolinska Institute, Karolinska University Hospital Solna, Center for Molecular Medicine/Translational Neuropharmacology, Solna, Sweden. Electronic address: Per.Svenningsson@ki.se.
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003863:Depression / Q000150:complications* / Q000188:drug therapy / Q000473:pathology / Q000534:rehabilitation; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005473:Fluoxetine; D005518:Food Preferences; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D024101:Mitochondrial Proteins / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018687:Antidepressive Agents, Second-Generation; D024101:Mitochondrial Proteins; D005473:Fluoxetine; D012701:Serotonin; D013395:Sucrose; D000255:Adenosine Triphosphate; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Chronic unpredictable stress; Exercise; Fluoxetine; Mitochondrial function; Serotonin