A unique combination of micronutrients rejuvenates cognitive performance in aged mice

Sam D Perez, Kristy Du, Catarina Rendeiro, Lin Wang, Qian Wu, Stanislav S Rubakhin, Rema Vazhappilly, Jeffrey H Baxter, Jonathan V Sweedler, Justin S Rhodes

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)97-112
Number of pages16
JournalBehavioural Brain Research
Early online date2 Dec 2016
Publication statusPublished - 1 Mar 2017


  • Age Factors
  • Aging
  • Animals
  • Avoidance Learning
  • Body Weight
  • Cognition
  • Cohort Studies
  • Cytokines
  • DNA Copy Number Variations
  • DNA, Mitochondrial
  • Eating
  • Female
  • Gene Expression Regulation
  • Hippocampus
  • Lipid Metabolism
  • Male
  • Metabolome
  • Mice
  • Mice, Inbred C57BL
  • Micronutrients
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Sex Factors
  • Journal Article


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