Abstract
Dietary supplementation with fruit or vegetable extracts can ameliorate age-related declines in measures of learning, memory, motor performance, and neuronal signal transduction in a rat model. To date, blueberries have proved most effective at improving measures of motor performance, spatial learning and memory, and neuronal functioning in old rats. In an effort to further characterize the bioactive properties of fruits rich in color and correspondingly high in anthocyanins and other polyphenolics, 19-month-old male Fischer rats were fed a well-balanced control diet, or the diet supplemented with 2% extract from either blueberry, cranberry, blackcurrant, or Boysenberry fruit for eight weeks before testing began. The blackcurrant and cranberry diets enhanced neuronal signal transduction as measured by striatal dopamine release, while the blueberry and cranberry diets were effective in ameliorating deficits in motor performance and hippocampal HSP70 neuroprotection; these changes in HSP70 were positively correlated with performance on the inclined screen. It appears that the polyphenols in blueberries and cranberries have the ability to improve muscle tone, strength and balance in aging rats, whereas polyphenols in blueberries, cranberries and blackcurrants have the ability to enhance neuronal functioning and restore the brain’s ability to generate a neuroprotective response to stress.
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Andres-Lacueva C, Shukitt-Hale B, Galli RL, Jauregui O, Lamuela-Raventos RM and Joseph JA (in press) Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci
Bickford PC, Gould T, Briederick L, Chadman K, Pollock A, Young D, Shukitt-Hale B and Joseph JA (2000) Antioxidant-rich diets improve cerebellar physiology and motor learning in aged rats. Brain Res 866: 211–217
Brandeis R, Brandys Y and Yehuda S (1989) The use of the Morris Water Maze in the study of memory and learning. Int J Neurosci 48: 29–69
Cantuti-Castelvetri I, Shukitt-Hale B and Joseph JA (2000) Neurobehavioral aspects of antioxidants in aging. Int J Dev Neurosci 18: 367–381
Cantuti-Castelvetri I, Shukitt-Hale B and Joseph JA (2003) Dopamine neurotoxicity: age-dependent behavioral and histological effects. Neurobiol Aging 24: 697–706
Carney JM, Smith CD, Carney AM and Butterfield DA (1994) Aging- and oxygen-induced modifications in brain biochemistry and behavior. Ann NY Acad Sci 738: 44–53
Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P and Dartigues JF (2000) Intake of flavonoids and risk of dementia. Eur J Epidemiol 16: 357–363
Connor AM, McGhie TK, Stephens JM, Hall HK and Alspach PA (in press) Variation and heritability estimates of anthocyanins and their relationship to antioxidant activity in a red raspberry factorial mating design. J Am Soc Hortic Sci
Denisova NA, Erat SA, Kelly JF and Roth GS (1998) Differential effect of aging on cholesterol modulation of carbachol stimulated low-Km GTPase in striatal synaptosomes. Exp Gerontol 33: 249–265
Deschamps V, Barberger-Gateau P, Peuchant E and Orgogozo JM (2001) Nutritional factors in cerebral aging and dementia: epidemiological arguments for a role of oxidative stress. Neuroepidemiology 20: 7–15
Floyd RA (1999) Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 222: 236–245
Galli RL, Bielinski DF, Szprengiel A, Shukitt-Hale B and Joseph JA (in press) Blueberry supplemented diet reverses age-related decline in hippocampal HSP 70 neuroprotection. Neurobiol Aging
Gilissen EP, Jacobs RE and Allman JM (1999) Magnetic resonance microscopy of iron in the basal forebrain cholinergic structures of the aged mouse lemur. J Neurol Sci 168: 21–27
Gordon SA, Hoffman RA, Simmons RL and Ford HR (1997) Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis. Arch Surg 132(12): 1277–1282
Guo ZH and Mattson MP (2000) In vivo 2-deoxyglucose administration preserves glucose and glutamate transport and mitochondrial function in cortical synaptic terminals after exposure to amyloid B-peptide and iron. Exp Neurol 166: 173–179
Ingram DK, Jucker M and Spangler E (1994) Behavioral manifestations of aging. In: Mohr U, Cungworth DL and Capen CC (eds) Pathobiology of the Aging Rat, pp 149–170, Vol 2. ILSI Press, Washington, DC
Joseph JA, Bartus RT, Clody DE, Morgan D, Finch C, Beer B and Sesack S (1983) Psychomotor performance in the senescent rodent: reduction of deficits via striatal dopamine receptor up-regulation. Neurobiol Aging 4: 313–319
Joseph JA, Dalton TK and Hunt WA (1998a) Age-related decrements in the muscarinic enhancement of K+-evoked release of endogenous striatal dopamine: an indicator of altered cholinergic–dopaminergic reciprocal inhibitory control in senescence. Brain Res 454: 140–148
Joseph JA, Dalton TK, Roth GS and Hunt WA (1988b) Alterations in muscarinic control of striatal dopamine autoreceptors in senescence: a deficit at the ligand–muscarinic receptor interface? Brain Res 454: 149–155
Joseph JA, Kowatch MA, Maki T and Roth GS (1990) Selective cross activation/inhibition of second messenger systems and the reduction of age-related deficits in the muscarinic control of dopamine release from perifused rat striata. Brain Res 537: 40–48
Joseph JA, Villalobos-Molina R, Denisova N, Erat S, Cutler R and Strain JG (1996) Age differences in sensitivity to H2O2- or NO-induced reductions in K+-evoked dopamine release from superfused striatal slices: reversals by PBN or Trolox. Free Radic Biol Med 20: 821–830
Joseph JA, Denisova N, Fisher D, Bickford P, Prior R and Cao G (1998a) Age-related neuro-degeneration and oxidative stress: putative nutritional intervention. Neurol Clin 16: 747–755
Joseph JA, Denisova NA, Fisher D, Shukitt-Hale B, Bickford P, Prior R and Cao G (1998b) Membrane and receptor modifications of oxidative stress vulnerability in aging: nutritional considerations. Ann NY Acad Sci 854: 268–276
Joseph JA, Shukitt-Hale B, Denisova NA, Prior RL, Cao G, Martin A, Taglialatela G and Bickford PC (1998c) Long term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age related neuronal signal-transduction and cognitive behavioral deficits. J Neurosci 18: 8047–8055
Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ and Bickford PC (1999) Reversals of age-related declines in neuronal signal transduction cognitive and motor behavioral deficits with blueberry spinach or strawberry dietary supplementation. J Neurosci 19: 8114–8121
Joseph JA, Fisher DR and Carey AN (2004) Fruit extracts antagonize AB- or DA-induced deficits in Ca2+ flux in M1-transfected COS-7 cells. J Alzheimer’s Dis 6: 403–411
Kalt W, Forney CF, Martin A and Prior RL (1999) Antioxidant capacity, vitamin C, phenolics, and anthocyanins after fresh storage of small fruits. J Agric Food Chem 47: 4638–4644
Lowenstein DH, Chan PH and Miles MF (1991) The stress protein response in cultured neurons: characterization and evidence for a protective role in excitotoxity. Neuron 7: 1053–1060
Lowry OH, Rosebrough NJ, Farr AL and Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 256–275
Mendelson KG, Contois L-R, Tevosian GG, Davis RJ and Paulson KE (1996) Independent regulation of JNK/p38 mitogen-activated protein kinases by metabolic oxidative stress in the liver. Proc Natl Acad Sci USA 93: 12908–1213
Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11: 47–60
Olanow CW (1992) An introduction to the free radical hypothesis in Parkinson’s disease. Ann Neurol 32: S2–S9
Sadoul R (1998) Bcl-2 family members in the development and degenerative pathologies of the nervous system. Cell Death Differ 5: 805–815
Savory J, Rao JK, Huang Y, Letada PR and Herman MM (1999) Age-related hippocampal changes in Bcl-2:Bax ratio, oxidative stress, redox-active iron and apoptosis associated with aluminum-induced neurodegeneration: increased susceptibility with aging. Neurotoxicology 20: 805–817
Seeram NP, Bourquin LD and Nair MG (2001a) Degradation products of cyanidin glycosides from tart cherries and their bioactivities. J Agric Food Chem 491: 4924–4929
Seeram NP, Momin RA, Bourquin LD and Nair MG (2001b) Cyclooxygenase inhibitory and antioxidant cyanidin glycosides in cherries and berries. Phytomedicine 8: 362–369
Seeram NP, Schutzki R, Chandra A and Nair MG (2002) Characterization, quantification, and bioactivities of anthocyanins in Cornus species. J Agric Food Chem 50: 2519–2523
Seeram NP, Cichewicz RH, Chandra A and Nair MG (2003) Cyclooxygenase inhibitory and antioxidant compounds from crabapple fruits. J Agric Food Chem 51: 1948–1951
Sharp FR, Massa SM and Swanson RA (1999) Heat shock protein protection. Trends Neurosci 22: 97–99
Shukitt-Hale B, Mouzakis G and Joseph JA (1998) Psychomotor and spatial memory performance in aging male Fischer 344 rats. Exp Gerontol 33: 615–624
Wang H, Nair MG, Strasburg GM, Chang Y, Booren AM, Gray JI and DeWitt DL (1999) Antioxidant and anti-inflammatory activities of anthocyanins and their aglycon, cyanidin, from tart cherries. J Nat Prod 62: 294–296
Youdim KA and Joseph JA (2001) A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radic Biol Med 30: 583–594
Youdim KA, Shukitt-Hale B, Martin A, Wang H, Denisova N, Bickford PC and Joseph JA (2000) Short term dietary supplementation of blueberry polyphenolics: beneficial effects on aging brain performance and peripheral tissue function. Nutr Neurosci 3: 383–397
Yu BP (1994) Cellular defenses against damage from reactive oxygen species. Physiol Rev 76: 139–162
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Shukitt-Hale, B., Galli, R.L., Meterko, V. et al. Dietary supplementation with fruit polyphenolics ameliorates age-related deficits in behavior and neuronal markers of inflammation and oxidative stress. AGE 27, 49–57 (2005). https://doi.org/10.1007/s11357-005-4004-9
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DOI: https://doi.org/10.1007/s11357-005-4004-9