title: Exercise prevents high-fat diet-induced impairment of flexible memory expression in the water maze and modulates adult hippocampal neurogenesis in mice.
abstract: Obesity is currently one of the most serious threats to human health in the western civilization. A growing body of evidence suggests that obesity is associated with cognitive dysfunction. Physical exercise not only improves fitness but it has also been shown in human and animal studies to increase hippocampus-dependent learning and memory. High-fat diet (HFD)-induced obesity and physical exercise both modulate adult hippocampal neurogenesis. Adult neurogenesis has been demonstrated to play a role in hippocampus-dependent learning and memory, particularly flexible memory expression. Here, we investigated the effects of twelve weeks of HFD vs. control diet (CD) and voluntary physical activity (wheel running; -R) vs. inactivity (sedentary; -S) on hippocampal neurogenesis and spatial learning and flexible memory function in female C57Bl/6 mice assessed in the Morris water maze. HFD was initiated either in adolescent mice combined with long-term concurrent exercise (preventive approach) or in young adult mice with 14days of subsequent exercise (therapeutic approach). HFD resulted in impaired flexible memory expression only when initiated in adolescent (HFD-S) but not in young adult mice, which was successfully prevented by concurrent exercise (HFD-R). Histological analysis revealed a reduction of immature neurons in the hippocampus of the memory-impaired HFD-S mice of the preventive approach. Long-term physical exercise also led to accelerated spatial learning during the acquisition period, which was accompanied by increased numbers of newborn mature neurons (HFD-R and CD-R). Short-term exercise of 14days in the therapeutic group was not effective in improving spatial learning or memory. We show that (1) alterations in learning and flexible memory expression are accompanied by changes in the number of neuronal cells at different maturation stages; (2) these neuronal cells are in turn differently affected by HFD; (3) adolescent mice are specifically susceptible to the negative effects of HFD. Thus, physical exercise, by modulating adult neurogenesis in the hippocampus, might represent a potential preventive approach for treating cognitive impairments associated with adolescent obesity.
authors.affiliation: Charité - University Medicine, Department of Neurology, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.affiliation: German Institute of Human Nutrition, Department of Experimental Diabetology, Potsdam-Rehbrücke, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Jonas
authors.affiliation: Charité - University Medicine, Department of Neurology, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Iggena
authors.affiliation: Charité - University Medicine, Department of Neurology, Berlin, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Empl
authors.affiliation: Humboldt University, Department of Biology, Neurocognitive Biology, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rivalan
authors.affiliation: German Institute of Human Nutrition, Department of Experimental Diabetology, Potsdam-Rehbrücke, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Wiedmer
authors.affiliation: Charité - University Medicine, Department of Endocrinology, Diabetes and Nutritional Medicine, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Spranger
authors.affiliation: Charité - University Medicine, Department of Psychiatry, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hellweg
authors.affiliation: Humboldt University, Department of Biology, Neurocognitive Biology, Berlin, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Winter
authors.affiliation: Charité - University Medicine, Department of Neurology, Berlin, Germany. Electronic address: barbara.steiner@charite.de.
authors.forename: B
authors.initials: B
authors.lastname: Steiner
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D018782:Maze Learning / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013997:Time Factors
keywords: Adult neurogenesis; Hippocampus; Learning and memory; Obesity; Physical exercise