title: Voluntary wheel running, but not a diet containing (-)-epigallocatechin-3-gallate and β-alanine, improves learning, memory and hippocampal neurogenesis in aged mice.
abstract: Aging is associated with impaired learning and memory accompanied by reductions in adult hippocampal neurogenesis and brain expression of neurotrophic factors among other processes. Epigallocatechin-3-gallate (EGCG, a green tea catechin), β-alanine (β-ala, the precursor of carnosine), and exercise have independently been shown to be neuroprotective and to reduce inflammation and oxidative stress in the central nervous system. We hypothesized that EGCG, β-ala supplementation or exercise alone would improve learning and memory and increase neurogenesis in aged mice, and the combined intervention would be better than either treatment alone. Male Balb/cByJ mice (19 months) were given AIN-93M diet with or without EGCG (182mg/kg/d) and β-ala (417mg/kg/d). Half of the mice were given access to a running wheel (VWR). The first 10 days, animals received 50mg/kg bromodeoxyuridine (BrdU) daily. After 28 days, learning and memory was assessed by Morris water maze (MWM) and contextual fear conditioning (CFC). Brains were collected for immunohistochemical detection of BrdU and quantitative mRNA expression in the hippocampus. VWR increased the number of BrdU cells in the dentate gyrus, increased expression of brain-derived neurotrophic factor, decreased expression of the inflammatory cytokine interleukin-1β, and improved performance in the MWM and CFC tests. The dietary intervention reduced brain oxidative stress as measured by 4-hydroxynonenal in the cerebellum, but had no effect on BrdU labeling or behavioral performance. These results suggest that exercise, but not a diet containing EGCG and β-ala, exhibit pro-cognitive effects in aged mice when given at these doses in this relatively short time frame.
authors.affiliation: Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Integrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Trisha E
authors.initials: TE
authors.lastname: Gibbons
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Integrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Brandt D
authors.initials: BD
authors.lastname: Pence
authors.affiliation: Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Integrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Petr
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Ossyra
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Houston C
authors.initials: HC
authors.lastname: Mach
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Tushar K
authors.initials: TK
authors.lastname: Bhattacharya
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Perez
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Integrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Martin
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Integrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: McCusker
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Integrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Kelley
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Integrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Justin S
authors.initials: JS
authors.lastname: Rhodes
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Integrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Johnson
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Integrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: woods1@illinois.edu.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Woods
mesh_terms: D000375:Aging / Q000502:physiology* / Q000523:psychology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003213:Conditioning, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D012420:Running / Q000502:physiology; D014836:Volition; D015091:beta-Alanine / Q000008:administration & dosage*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015091:beta-Alanine; D002392:Catechin; C045651:epigallocatechin gallate
keywords: Aging; Cognition; Diet; Exercise; Learning; Mice