title: Moderate exercise ameliorates dysregulated hippocampal glycometabolism and memory function in a rat model of type 2 diabetes.
abstract: Type 2 diabetes is likely to be an independent risk factor for hippocampal-based memory dysfunction, although this complication has yet to be investigated in detail. As dysregulated glycometabolism in peripheral tissues is a key symptom of type 2 diabetes, it is hypothesised that diabetes-mediated memory dysfunction is also caused by hippocampal glycometabolic dysfunction. If so, such dysfunction should also be ameliorated with moderate exercise by normalising hippocampal glycometabolism, since 4 weeks of moderate exercise enhances memory function and local hippocampal glycogen levels in normal animals.
  
  
  
  The hippocampal glycometabolism in OLETF rats (model of human type 2 diabetes) was assessed and, subsequently, the effects of exercise on memory function and hippocampal glycometabolism were investigated.
  
  
  
  OLETF rats, which have memory dysfunction, exhibited higher levels of glycogen in the hippocampus than did control rats, and breakdown of hippocampal glycogen with a single bout of exercise remained unimpaired. However, OLETF rats expressed lower levels of hippocampal monocarboxylate transporter 2 (MCT2, a transporter for lactate to neurons). Four weeks of moderate exercise improved spatial memory accompanied by further increase in hippocampal glycogen levels and restoration of MCT2 expression independent of neurotrophic factor and clinical symptoms in OLETF rats.
  
  
  
  Our findings are the first to describe detailed profiles of glycometabolism in the type 2 diabetic hippocampus and to show that 4 weeks of moderate exercise improves memory dysfunction in type 2 diabetes via amelioration of dysregulated hippocampal glycometabolism. Dysregulated hippocampal lactate-transport-related glycometabolism is a possible aetiology of type-2-diabetes-mediated memory dysfunction.
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8574, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Shima
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8574, Japan.|Department of Sports Neuroscience, Advanced Research Initiative for Human High Performance (ARIHHP), University of Tsukuba, Tsukuba, Ibaraki, Japan.|Cajal Institute, CSIC, Madrid, Spain.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8574, Japan.|Department of Sports Neuroscience, Advanced Research Initiative for Human High Performance (ARIHHP), University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Subrina
authors.initials: S
authors.lastname: Jesmin
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8574, Japan.|Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8574, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Soya
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8574, Japan.
authors.forename: Koshiro
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8574, Japan.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Cajal Institute, CSIC, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Torres-Aleman
authors.affiliation: Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8574, Japan. hsoya@taiiku.tsukuba.ac.jp.|Department of Sports Neuroscience, Advanced Research Initiative for Human High Performance (ARIHHP), University of Tsukuba, Tsukuba, Ibaraki, Japan. hsoya@taiiku.tsukuba.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Soya
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D004435:Eating / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D020334:Rats, Inbred OLETF
chemical_list: D001786:Blood Glucose; D006003:Glycogen
keywords: Exercise; Glycogen; Hippocampus; Monocarboxylate transporter 2; Spatial memory; Type 2 diabetes mellitus