title: A unique combination of micronutrients rejuvenates cognitive performance in aged mice.
abstract: It is widely believed that diet can influence the onset and severity of cognitive aging, but the optimal combination of micronutrients and molecular and cellular mechanisms remain elusive. The purpose of this study was to compare the effects of eight distinct diets, consisting of various concentrations of selected micronutrients, on learning and memory as well as markers of neuronal plasticity, and metabolic and neuro-immune status of the aged hippocampus. Eighteen-month-old male and female C57BL/6J mice were fed the diets for 16 weeks, followed by learning and memory trials on the active avoidance task. Number of immature neurons were measured by immunohistochemical detection of doublecortin (DCX+) in the granule layer of the dentate gyrus. Amount of mitochondrial DNA (mtDNA) and gene expression of molecular markers of mitochondrial biogenesis (Ppargc1α, Sirt1, Tfam), and neuroinflammation (IL-10, Alox15, Ptgs2, IL-1β, IL-6 and Tnf) were assessed by quantitative real time polymerase chain reaction (qRT-PCR) of hippocampal samples. Tissue levels of selected micronutrients and a number of metabolites were measured by liquid chromatography-mass spectrometry. The diet supplemented with RRR d-alpha tocopheryl acetate, citicholine, 5-methyltetrahydrofolic acid, quercetin and the n-3 fatty acid phosphatidylserine-docosahexaenoic acid, improved performance on the active avoidance learning and memory task compared to all the other less-complex diets. This diet also increased IL-10 expression and attenuated the age-related change in mtDNA content in the hippocampus without affecting metabolite levels. Results suggest cognitive benefits of wholesome diets are partially mediated through combined antioxidant and anti-inflammatory activities of optimized mixtures of micronutrients.
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA; Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign, USA.
authors.forename: Sam D
authors.initials: SD
authors.lastname: Perez
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, USA; Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign, USA.
authors.forename: Kristy
authors.initials: K
authors.lastname: Du
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA; Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign, USA.
authors.forename: Catarina
authors.initials: C
authors.lastname: Rendeiro
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA; Department of Chemistry, University of Illinois at Urbana-Champaign, USA; Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA; Department of Chemistry, University of Illinois at Urbana-Champaign, USA; Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA; Department of Chemistry, University of Illinois at Urbana-Champaign, USA; Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign, USA.
authors.forename: Stanislav S
authors.initials: SS
authors.lastname: Rubakhin
authors.affiliation: Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign, USA; Abbott Nutrition, Singapore.
authors.forename: Rema
authors.initials: R
authors.lastname: Vazhappilly
authors.affiliation: Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign, USA; Abbott Nutrition, Columbus OH, 43219, USA.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Baxter
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA; Department of Chemistry, University of Illinois at Urbana-Champaign, USA; Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign, USA.
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Sweedler
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, USA; Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign, USA. Electronic address: jrhodes@illinois.edu.
authors.forename: Justin S
authors.initials: JS
authors.lastname: Rhodes
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D056915:DNA Copy Number Variations / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004435:Eating / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D055442:Metabolome / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018977:Micronutrients / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D012737:Sex Factors
chemical_list: D016207:Cytokines; D004272:DNA, Mitochondrial; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018977:Micronutrients; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
keywords: Active avoidance; Aging; Diet; Hippocampus; Learning; Memory