title: Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats.
abstract: In metabolic syndrome (MetS), previous studies have suggested that cognitive decline is worsened. Among the factors associated with cognition, decreased brain-derived neurotrophic factor (BDNF) in the hippocampus causes cognitive decline. We previously reported that exercise training with calorie restriction yielded protection against cognitive decline via BDNF in the hippocampus of hypertensive rats. The aim of the present study was to determine whether or not calorie restriction results in protection against cognitive decline via BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of MetS model rats. We divided dietary-induced obesity-prone and hypertensive rats (OP), as metabolic syndrome model rats, into three groups, fed with a high fat diet (HF), treated with calorie restriction (CR) plus vehicle, and treated with CR and ANA-12 (a TrkB antagonist) (CR+A). After treatment for 28 days, body weight, insulin, fasting blood glucose, adiponectin, systolic blood pressure, and oxidative stress in the hippocampus were significantly lower, and BDNF expression in the hippocampus was significantly higher in CR and CR+A than in HF. Cognitive performance determined by the Morris water maze test was significantly higher in CR than in HF, whereas the benefit was attenuated in CR+A. In conclusion, calorie restriction protects against cognitive decline via up-regulation of BDNF/TrkB through an antioxidant effect in the hippocampus of dietary-induced obesity rats.
authors.affiliation: Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nagayama
authors.forename: Kengo
authors.initials: K
authors.lastname: Isegawa
authors.forename: Masato
authors.initials: M
authors.lastname: Katsuki
authors.forename: Ko
authors.initials: K
authors.lastname: Takesue
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D031204:Caloric Restriction / Q000379:methods*; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000378:metabolism / Q000517:prevention & control; D059305:Diet, High-Fat / Q000379:methods; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism; D009765:Obesity / Q000150:complications; D018384:Oxidative Stress / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011494:Protein Kinases; D020813:Receptor, trkB; C041311:tropomyosin kinase