A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer’s transgenic mice

Arendash, Gary W.; Jensen, Maren; Salem, Norman; Hussein, Nahed; Cracchiolo, Jennifer R.; Dickson, Alexander; Leighty, Ralph E.; Potter, Huntington

doi:10.1016/j.neuroscience.2007.08.018

Cited by 92 publications

(75 citation statements)

References 51 publications

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“…Recently, 2 interventional studies reported a significant cognitive improvement in patients suffering from mild cognitive impairment (MCI) after intake of omega-3 polyUFA supplements vs. placebo (28,29). However, inconclusive or negative findings from animal and observational studies have also been reported for CR (e.g., 30,31,32) and UFAs (33,34).…”

mentioning

confidence: 99%

Caloric restriction improves memory in elderly humans

Witte¹,

Fobker²,

Gellner³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

497

378

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Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m2) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchanged total fat), and (iii) control. Before and after 3 months of intervention, memory performance was assessed under standardized conditions. We found a significant increase in verbal memory scores after caloric restriction (mean increase 20%; P < 0.001), which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein, most pronounced in subjects with best adherence to the diet (all r values < −0.8; all P values <0.05). Levels of brain-derived neurotrophic factor remained unchanged. No significant memory changes were observed in the other 2 groups. This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects. Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity. Our study may help to generate novel prevention strategies to maintain cognitive functions into old age

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mentioning

confidence: 99%

Caloric restriction improves memory in elderly humans

Witte¹,

Fobker²,

Gellner³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

497

378

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“…A donut-shaped 0.5 mm-thick silicone splint was concentric with a wound and fi xed to the skin surrounding the wound with an immediate-bonding adhesive (Krazy Glue ® ) and 6-0 nylon sutures; and then a transparent sterile occlusive dressing then was placed over the wound and the splint ( 20 ). Mice were fed with a standard chow diet Teklad 2018 containing 0% DHA and 2.76% 3 ␣ -linolenic acid of total fatty acids ( 21 ). ␣ -linolenic acid can be converted to DHA in rodents ( 22 ).…”

Section: Murine Splinted Excisional Wound Healing Modelmentioning

confidence: 99%

Novel 14,21-dihydroxy-docosahexaenoic acids: structures, formation pathways, and enhancement of wound healing

Lü

Tian

Hong

2010

Journal of Lipid Research

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“…Some studies have shown that spatial learning capacity is altered in x3-deficient old rodents (Yamamoto et al, 1991;Umezawa et al, 1995;Carrie et al, 2002), while x3 LC-PUFA supplementation (fish oil) improves learning in old rats (Gamoh et al, 2001;Kelly et al, 2010) and in rodent models of Alzheimer's disease (Calon et al, 2004;Hashimoto et al, 2011), with some contradictory results (Barcelo-Coblijn et al, 2003;Arendash et al, 2007;Moranis et al, 2011). The beneficial effect of acute fish oil supplementation seems to be partly attributable to the anti-oxidative and anti-inflammatory actions of x3 LC-PUFA (review Boudrault et al, 2009), but little is known about the physiological mechanism linking cognitive decline and chronic x3 deficiency.…”

Section: Introductionmentioning

confidence: 99%

Omega‐3 fatty acids deficiency aggravates glutamatergic synapse and astroglial aging in the rat hippocampal CA1

Latour¹,

Grintal²,

Champeil‐Potokar³

et al. 2012

Aging Cell

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SummaryEpidemiological data suggest that a poor x3 status favoured by the low x3/x6 polyunsaturated fatty acids ratio in western diets contributes to cognitive decline in the elderly, but mechanistic evidence is lacking. We therefore explored the impact of x3 deficiency on the evolution of glutamatergic transmission in the CA1 of the hippocampus during aging by comparing 4 groups of rats aged 6-22 months fed x3-deficient or x3/x6-balanced diets from conception to sacrifice: Young x3 Balanced (YB) or Deficient (YD), Old x3 Balanced (OB) or Deficient (OD) rats. x3 Deficiency induced a 65% decrease in the amount of docosahexaenoic acid (DHA, the main x3 in cell membranes) in brain phospholipids, but had no impact on glutamatergic transmission and astroglial function in young rats. Aging induced a 10% decrease in brain DHA, a 35% reduction of synaptic efficacy (fEPSP/PFV) due to decreased presynaptic glutamate release and a 30% decrease in the astroglial glutamate uptake associated with a marked astrogliosis (+100% GFAP). The x3 deficiency further decreased these hallmarks of aging (OD vs. OB rats: À35% fEPSP/PFV P < 0.05, À15% astroglial glutamate uptake P < 0.001, +30% GFAP P < 0.01). This cannot be attributed to aggravation of the brain DHA deficit because the brains of OD rats had more DHA than those of YD rats. Thus, x3 deficiency worsens the age-induced degradation of glutamatergic transmission and its associated astroglial regulation in the hippocampus.

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A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer’s transgenic mice

Cited by 92 publications

References 51 publications

Caloric restriction improves memory in elderly humans

Caloric restriction improves memory in elderly humans

Novel 14,21-dihydroxy-docosahexaenoic acids: structures, formation pathways, and enhancement of wound healing

Omega‐3 fatty acids deficiency aggravates glutamatergic synapse and astroglial aging in the rat hippocampal CA1

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