Intake of Wild Blueberry Powder Improves Episodic-Like and Working Memory during Normal Aging in Mice

Abstract

The number of Americans older than 65 years old is projected to more than double in the next 40 years. Cognitive changes associated to aging can affect an adultʼs day-to-day functioning. Among these cognitive changes, reasoning, episodic memory, working memory, and processing speed decline gradually over time. Early memory changes include a decline in both working and episodic memory. The aim of the present study was to determine whether chronic (up to 75 days) daily administration of wild blueberry extract or a wild blueberry full spectrum powder would help prevent memory failure associated with aging in tasks involving various forms of memory. Both blueberry ingredients were used in a study comparing young mice (6 months old) to aged mice (18 months old). At this age, mice exhibit memory decline due to aging, which is exacerbated first by a loss in working and contextual (episodic-like) memory. Contextual memory (episodic-like memory) was evaluated using the contextual serial discrimination test. Working and spatial memory were evaluated using the Morris-Water maze test and the sequential alternation test. Statistical analysis was performed using an ANOVA with the Bonferroni post-hoc test. Supplementation with wild blueberry full spectrum powder and wild blueberry extract resulted in significant improvement of contextual memory, while untreated aged mice experienced a decline in such memory. Only the wild blueberry full spectrum powder significantly contributed to an improvement of spatial and working memory versus untreated aged mice. These improvements of cognitive performance may be related to brain oxidative status, acetylcholinesterase activity, neuroprotection, or attenuation of immunoreactivity.

Key words

wild blueberry - episodic memory - working memory - aging - serial contextual discrimination - alternation

• References

• 1 Harada CN, Natelson Love MC, Triebel KL. Normal cognitive aging. Clin Geriatr Med 2013; 29: 737-752
• 2 Pause BM, Zlomuzica A, Kinugawa K, Mariani J, Pietrowsky R, Dere E. Perspectives on episodic-like and episodic memory. Front Behav Neurosci 2013; 7: 33
• 3 de Jager CA, Dye L, de Bruin EA, Butler L, Fletcher J, Lamport DJ, Latulippe ME, Spencer JP, Wesnes K. Criteria for validation and selection of cognitive tests for investigating the effects of foods and nutrients. Nutr Rev 2014; 72: 162-179
• 4 Flak MM, Hernes SS, Skranes J, Løhaugen GC. The Memory Aid study: protocol for a randomized controlled clinical trial evaluating the effect of computer-based working memory training in elderly patients with mild cognitive impairment (MCI). Trials 2014; 15: 156
• 5 Summers WK, Martin RL, Cunningham M, DeBoynton VL, Marsh GM. Complex antioxidant blend improves memory in community-dwelling seniors. J Alzheimers Dis 2010; 19: 429-439
• 6 Sweeney MI, Kalt W, MacKinnon SL, Ashby J, Gottschall-Pass KT. Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage. Nutr Neurosci 2002; 5: 427-431
• 7 Willis LM, Small BJ, Bickford PC, Umphlet CD, Moore AB, Granholm AC. Dietary blueberry supplementation affects growth but not vascularization of neural transplants. J Cereb Blood Flow Metab 2008; 28: 1150-1164
• 8 Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, Joseph JA. Blueberry supplementation improves memory in older adults. J Agric Food Chem 2010; 58: 3996-4000
• 9 Andres-Lacueva C, Shukitt-Hale B, Galli RL, Jauregui O, Lamuela-Raventos RM, Joseph JA. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci 2005; 8: 111-120
• 10 Goyarzu P, Malin DH, Lau FC, Taglialatela G, Moon WD, Jennings R, Moy E, Moy D, Lippold S, Shukitt-Hale B, Joseph JA. Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Nutr Neurosci 2004; 7: 75-83
• 11 Rendeiro C, Vauzour D, Kean RJ, Butler LT, Rattray M, Spencer JP, Williams CM. Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats. Psychopharmacology (Berl) 2012; 223: 319-330
• 12 Shukitt-Hale B, Lau FC, Carey AN, Galli RL, Spangler EL, Ingram DK, Joseph JA. Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. Nutr Neurosci 2008; 11: 172-182
• 13 Tronche C, Lestage P, Louis C, Carrie I, Béracochéa D. Pharmacological modulation of contextual “episodic-like” memory in aged mice. Behav Brain Res 2010; 215: 255-260
• 14 Célérier A, Piérard C, Rachbauer D, Sarrieau A, Béracochéa D. Contextual and serial discriminations: a new learning paradigm to assess simultaneously the effects of acute stress on retrieval of flexible or stable information in mice. Learn Mem 2004; 11: 196-204
• 15 Vandesquille M. Implication du systeme cholinergique dans lʼalteration de la memoire de travail au cours du viellissement chez la souris [dissertation]. Bordeaux: Universite de Bordeaux; 2011
• 16 Rendeiro C, Vauzour D, Rattray M, Waffo-Téguo P, Mérillon JM, Butler LT, Williams CM, Spencer JP. Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor. PLoS One 2013; 8: e63535
• 17 Kalt W, Liu Y, McDonald JE, Vinqvist-Tymchuk MR, Fillmore SA. Anthocyanin metabolites are abundant and persistent in human urine. J Agric Food Chem 2014; 62: 3926-3934
• 18 Shukitt-Hale B. Blueberries and neuronal aging. Gerontology 2012; 58: 518-523
• 19 Ribnicky DM, Roopchand DE, Oren A, Grace M, Poulev A, Lila MA, Havenaar R, Raskin I. Effects of a high fat meal matrix and protein complexation on the bioaccessibility of blueberry anthocyanins using the TNO gastrointestinal model (TIM-1). Food Chem 2014; 142: 349-357
• 20 Harada N, Zhao J, Kurihara H, Nakagata N, Okajima K. Resveratrol improves cognitive function in mice by increasing production of insulin-like growth factor-I in the hippocampus. J Nutr Biochem 2011; 22: 1150-1159
• 21 Fang J. Bioavailability of anthocyanins. Drug Metab Rev 2014; 46: 508-520
• 22 Spencer JP. Flavonoids and brain health: multiple effects underpinned by common mechanisms. Genes Nutr 2009; 4: 243-250
• 23 Casadesus G, Shukitt-Hale B, Stellwagen HM, Zhu X, Lee HG, Smith MA, Josphe JA. Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci 2004; 7: 309-316
• 24 Murphy T, Dias GP, Thuret S. Effects of diet on brain plasticity in animal and human studies: mind the gap. Neural Plast 2014; 2014: 563160
• 25 Williams CM, El Mohsen MA, Vauzour D, Rendeiro C, Butler LT, Ellis JA, Whiteman M, Spencer JP. Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels. Free Radic Biol Med 2008; 45: 295-305
• 26 Béracochéa DJ, Jaffard R. Impairment of spontaneous alternation behavior in sequential test procedures following mammillary body lesions in mice: evidence for time-dependent interference-related memory deficits. Behav Neurosci 1987; 101: 187-197
• 27 Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984; 11: 47-60