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Polyphenol-rich extract from grape and blueberry attenuates cognitive decline and improves neuronal function in aged mice

  • Julien Bensalem (a1) (a2) (a3), Stéphanie Dudonné (a4) (a5), David Gaudout (a3), Laure Servant (a1) (a2), Frédéric Calon (a4) (a5) (a6), Yves Desjardins (a4) (a5), Sophie Layé (a1) (a2) (a5), Pauline Lafenetre (a1) (a2) (a5) (a7) and Véronique Pallet (a1) (a2) (a5) (a7)...
Abstract

Ageing is characterised by memory deficits, associated with brain plasticity impairment. Polyphenols from berries, such as flavan-3-ols, anthocyanins, and resveratrol, have been suggested to modulate synaptic plasticity and cognitive processes. In the present study we assessed the preventive effect of a polyphenol-rich extract from grape and blueberry (PEGB), with high concentrations of flavonoids, on age-related cognitive decline in mice. Adult and aged (6 weeks and 16 months) mice were fed a PEGB-enriched diet for 14 weeks. Learning and memory were assessed using the novel object recognition and Morris water maze tasks. Brain polyphenol content was evaluated with ultra-high-performance LC-MS/MS. Hippocampal neurotrophin expression was measured using quantitative real-time PCR. Finally, the effect of PEGB on adult hippocampal neurogenesis was assessed by immunochemistry, counting the number of cells expressing doublecortin and the proportion of cells with dendritic prolongations. The combination of grape and blueberry polyphenols prevented age-induced learning and memory deficits. Moreover, it increased hippocampal nerve growth factor (Ngf) mRNA expression. Aged supplemented mice displayed a greater proportion of newly generated neurons with prolongations than control age-matched mice. Some of the polyphenols included in the extract were detected in the brain in the native form or as metabolites. Aged supplemented mice also displayed a better survival rate. These data suggest that PEGB may prevent age-induced cognitive decline. Possible mechanisms of action include a modulation of brain plasticity. Post-treatment detection of phenolic compounds in the brain suggests that polyphenols may act directly at the central level, while they can make an impact on mouse survival through a potential systemic effect.

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Copyright
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
*Corresponding author: Professor Véronique Pallet, fax +33 5 57 57 12 27, email veronique.pallet@enscbp.fr
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These authors contributed equally to this work.

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References
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1.Yurko-Mauro, K, McCarthy, D, Rom, D, et al. (2010) Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement 6, 456464.
2.Nooyens, AC, Milder, IE, van Gelder, BM, et al. (2015) Diet and cognitive decline at middle age: the role of antioxidants. Br J Nutr 113, 14101417.
3.Joseph, JA, Shukitt-Hale, B & Casadesus, G (2005) Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr 81, 313S316S.
4.Queen, BL & Tollefsbol, TO (2010) Polyphenols and aging. Curr Aging Sci 3, 3442.
5.Manach, C, Scalbert, A, Morand, C, et al. (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79, 727747.
6.Krikorian, R, Nash, TA, Shidler, MD, et al. (2010) Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr 103, 730734.
7.Krikorian, R, Shidler, MD, Nash, TA, et al. (2010) Blueberry supplementation improves memory in older adults. J Agric Food Chem 58, 39964000.
8.Bensalem, J, Servant, L, Alfos, S, et al. (2016) Dietary polyphenol supplementation prevents alterations of spatial navigation in middle-aged mice. Front Behav Neurosci 10, 9.
9.Dudonné, S, Dal-Pan, A, Dubé, P, et al. (2016) Potentiation of the bioavailability of blueberry phenolic compounds by co-ingested grape phenolic compounds in mice, revealed by targeted metabolomic profiling in plasma and feces. Food Funct 7, 34213430.
10.Spencer, JP (2007) The interactions of flavonoids within neuronal signalling pathways. Genes Nutr 2, 257273.
11.An, L, Zhang, YZ, Yu, NJ, et al. (2008) The total flavonoids extracted from Xiaobuxin-Tang up-regulate the decreased hippocampal neurogenesis and neurotrophic molecules expression in chronically stressed rats. Prog Neuropsychopharmacol Biol Psychiatry 32, 14841490.
12.Dias, GP, Cavegn, N, Nix, A, et al. (2012) The role of dietary polyphenols on adult hippocampal neurogenesis: molecular mechanisms and behavioural effects on depression and anxiety. Oxid Med Cell Longev 2012, 541971.
13.Efferth, T & Koch, E (2011) Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy. Curr Drug Targets 12, 122132.
14.Dal-Pan, A, Dudonné, S, Bourassa, P, et al. (2017) Cognitive-enhancing effects of a polyphenols-rich extract from fruits without changes in neuropathology in an animal model of Alzheimer's disease. J Alzheimers Dis 55, 115135.
15.Gasperotti, M, Passamonti, S, Tramer, F, et al. (2015) Fate of microbial metabolites of dietary polyphenols in rats: is the brain their target destination? ACS Chem Neurosci 6, 13411352.
16.Touyarot, K, Bonhomme, D, Roux, P, et al. (2013) A mid-life vitamin A supplementation prevents age-related spatial memory deficits and hippocampal neurogenesis alterations through CRABP-I. PLOS ONE 8, e72101.
17.Lemaire, V, Lamarque, S, Le Moal, M, et al. (2006) Postnatal stimulation of the pups counteracts prenatal stress-induced deficits in hippocampal neurogenesis. Biol Psychiatry 59, 786792.
18.Bensalem, J, Dal-Pan, A, Gillard, E, et al. (2016) Protective effects of berry polyphenols against age-related cognitive impairment. Nutr Aging 3, 89106.
19.Han, YS, Bastianetto, S, Dumont, Y, et al. (2006) Specific plasma membrane binding sites for polyphenols, including resveratrol, in the rat brain. J Pharmacol Exp Ther 318, 238245.
20.Agarwal, B & Baur, JA (2011) Resveratrol and life extension. Ann N Y Acad Sci 1215, 138143.
21.Baur, JA & Sinclair, DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5, 493506.
22.Sadowska-Bartosz, I & Bartosz, G (2014) Effect of antioxidants supplementation on aging and longevity. Biomed Res Int 2014, 404680.
23.Del Rio, D, Rodriguez-Mateos, A, Spencer, JPE, et al. (2013) Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal 18, 18181892.
24.Carey, AN, Gomes, SM & Shukitt-Hale, B (2014) Blueberry supplementation improves memory in middle-aged mice fed a high-fat diet. J Agric Food Chem 62, 39723978.
25.Yokozawa, T, Lee, YA, Cho, EJ, et al. (2011) Anti-aging effects of oligomeric proanthocyanidins isolated from persimmon fruits. Drug Discov Ther 5, 109118.
26.Buffalo, EA, Bellgowan, PS & Martin, A (2006) Distinct roles for medial temporal lobe structures in memory for objects and their locations. Learn Mem 13, 638643.
27.Mumby, DG (2001) Perspectives on object-recognition memory following hippocampal damage: lessons from studies in rats. Behav Brain Res 127, 159181.
28.Squire, LR, Wixted, JT & Clark, RE (2007) Recognition memory and the medial temporal lobe: a new perspective. Nat Rev Neurosci 8, 872883.
29.Morris, RG, Garrud, P, Rawlins, JN, et al. (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297, 681683.
30.Frick, KM, Baxter, MG, Markowska, AL, et al. (1995) Age-related spatial reference and working memory deficits assessed in the water maze. Neurobiol Aging 16, 149160.
31.De Nicolo, S, Tarani, L, Ceccanti, M, et al. (2013) Effects of olive polyphenols administration on nerve growth factor and brain-derived neurotrophic factor in the mouse brain. Nutrition 29, 681687.
32.Schinder, AF & Poo, M (2000) The neurotrophin hypothesis for synaptic plasticity. Trends Neurosci 23, 639645.
33.Poo, MM (2001) Neurotrophins as synaptic modulators. Nat Rev Neurosci 2, 2432.
34.Fischer, W, Bjorklund, A, Chen, K, et al. (1991) NGF improves spatial memory in aged rodents as a function of age. J Neurosci 11, 18891906.
35.Woolf, NJ, Milov, AM, Schweitzer, ES, et al. (2001) Elevation of nerve growth factor and antisense knockdown of TrkA receptor during contextual memory consolidation. J Neurosci 21, 10471055.
36.Katoh-Semba, R, Semba, R, Takeuchi, IK, et al. (1998) Age-related changes in levels of brain-derived neurotrophic factor in selected brain regions of rats, normal mice and senescence-accelerated mice: a comparison to those of nerve growth factor and neurotrophin-3. Neurosci Res 31, 227234.
37.Gomez-Pinilla, F & Hillman, C (2013) The influence of exercise on cognitive abilities. Compr Physiol 3, 403428.
38.Calabrese, F, Guidotti, G, Racagni, G, et al. (2013) Reduced neuroplasticity in aged rats: a role for the neurotrophin brain-derived neurotrophic factor. Neurobiol Aging 34, 27682776.
39.Rendeiro, C, Vauzour, D, Rattray, M, et al. (2013) Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor. PLOS ONE 8, e63535.
40.Nyffeler, M, Yee, BK, Feldon, J, et al. (2010) Abnormal differentiation of newborn granule cells in age-related working memory impairments. Neurobiol Aging 31, 19561974.
41.Drapeau, E & Nora Abrous, D (2008) Stem cell review series: role of neurogenesis in age-related memory disorders. Aging Cell 7, 569589.
42.Deng, W, Aimone, JB & Gage, FH (2010) New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11, 339350.
43.Harada, N, Zhao, J, Kurihara, H, et al. (2011) Resveratrol improves cognitive function in mice by increasing production of insulin-like growth factor-I in the hippocampus. J Nutr Biochem 22, 11501159.
44.Shukitt-Hale, B, Bielinski, DF, Lau, FC, et al. (2015) The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing. Br J Nutr 114, 15421549.
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Journal of Nutritional Science
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