title: Synergistic effects of diet and exercise on hippocampal function in chronically stressed mice.
abstract: Severe chronic stress can have a profoundly negative impact on the brain, affecting plasticity, neurogenesis, memory and mood. On the other hand, there are factors that upregulate neurogenesis, which include dietary antioxidants and physical activity. These factors are associated with biochemical processes that are also altered in age-related cognitive decline and dementia, such as neurotrophin expression, oxidative stress and inflammation. We exposed mice to an unpredictable series of stressors or left them undisturbed (controls). Subsets of stressed and control mice were concurrently given (1) no additional treatment, (2) a complex dietary supplement (CDS) designed to ameliorate inflammation, oxidative stress, mitochondrial dysfunction, insulin resistance and membrane integrity, (3) a running wheel in each of their home cages that permitted them to exercise, or (4) both the CDS and the running wheel for exercise. Four weeks of unpredictable stress reduced the animals' preference for saccharin, increased their adrenal weights and abolished the exercise-induced upregulation of neurogenesis that was observed in non-stressed animals. Unexpectedly, stress did not reduce hippocampal size, brain-derived neurotrophic factor (BDNF), or neurogenesis. The combination of dietary supplementation and exercise had multiple beneficial effects, as reflected in the number of doublecortin (DCX)-positive immature neurons in the dentate gyrus (DG), the sectional area of the DG and hippocampal CA1, as well as increased hippocampal BDNF messenger ribonucleic acid (mRNA) and serum vascular endothelial growth factor (VEGF) levels. In contrast, these benefits were not observed in chronically stressed animals exposed to either dietary supplementation or exercise alone. These findings could have important clinical implications for those suffering from chronic stress-related disorders such as major depression.
authors.affiliation: Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: C P
authors.initials: CP
authors.lastname: Hutton
authors.affiliation: Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Déry
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Rosa
authors.affiliation: Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Lemon
authors.affiliation: Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: C D
authors.initials: CD
authors.lastname: Rollo
authors.affiliation: Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: D R
authors.initials: DR
authors.lastname: Boreham
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Fahnestock
authors.affiliation: Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: D
authors.initials: D
authors.lastname: deCatanzaro
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Wojtowicz
authors.affiliation: Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON L8S 4K1, Canada. Electronic address: becker@mcmaster.ca.
authors.forename: S
authors.initials: S
authors.lastname: Becker
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002908:Chronic Disease; D003866:Depressive Disorder / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology; D009929:Organ Size; D010805:Physical Conditioning, Animal / Q000502:physiology; D012420:Running / Q000502:physiology*; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D016896:Treatment Outcome; D035501:Uncertainty; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D042461:Vascular Endothelial Growth Factor A; C519530:insulin-like growth factor-1, mouse; C467480:vascular endothelial growth factor A, mouse; D007334:Insulin-Like Growth Factor I
keywords: dietary supplements; exercise; hippocampus; neurogenesis; psychological depression; stress