Antioxidants and cognitive training interact to affect oxidative stress and memory in APP/PSEN1 mice

Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-0475, USA.
Nutritional Neuroscience (Impact Factor: 2.27). 10/2009; 12(5):203-18. DOI: 10.1179/147683009X423364
Source: PubMed


The present study investigated the relationships among oxidative stress, beta-amyloid and cognitive abilities in the APP/PSEN1 double-transgenic mouse model of Alzheimer's disease. In two experiments, long-term dietary supplements were given to aged APP/PSEN1 mice containing vitamin C alone (1 g/kg diet; Experiment 1) or in combination with a high (750 IU/kg diet, Experiments 1 and 2) or lower (400 IU/kg diet, Experiment 2) dose of vitamin E. Oxidative stress, measured by F(4)-neuroprostanes or malondialdehyde, was elevated in cortex of control-fed APP/PSEN1 mice and reduced to wild-type levels by vitamin supplementation. High-dose vitamin E with C was less effective at reducing oxidative stress than vitamin C alone or the low vitamin E+C diet combination. The high-dose combination also impaired water maze performance in mice of both genotypes. In Experiment 2, the lower vitamin E+C treatment attenuated spatial memory deficits in APP/PSEN1 mice and improved performance in wild-type mice in the water maze. Amyloid deposition was not reduced by antioxidant supplementation in either experiment.

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Available from: Michael P McDonald, Apr 01, 2015
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    • "zone surrounding the former platform location was used as a measure of memory during the probe trial. This zone score was used as a more accurate measure of memory, compared to quadrant time (Bernardo et al., 2007; Dhanushkodi and McDonald, 2011; Flanigan et al., 2014; Harrison et al., 2009a). Because of the shape of the pool quadrants, some locations within the target quadrant are farther away from the platform location than other locations in neighboring quadrants. "
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    ABSTRACT: Physical exercise may provide protection against the cognitive decline and neuropathology associated with Alzheimer's disease, although the mechanisms are not clear. In the present study, APP/PSEN1 double-transgenic and wild-type mice were allowed unlimited voluntary exercise for 7 months. Consistent with previous reports, wheel-running improved cognition in the double-transgenic mice. Interestingly, the average daily distance run was strongly correlated with spatial memory in the water maze in wild-type mice (r 2 = .959), but uncorrelated in transgenics (r 2 = .013). Proteomics analysis showed that sedentary transgenic mice differed significantly from sedentary wild-types with respect to proteins involved in synaptic transmission, cytoskeletal regulation, and neurogenesis. When given an opportunity to exercise, the transgenics' deficiencies in cytoskeletal regulation and neurogenesis largely normalized, but abnormal synaptic proteins did not change. In contrast, exercise enhanced proteins associated with cytoskeletal regulation, oxidative phosphorylation, and synaptic transmission in wild-type mice. Soluble and insoluble Aβ40 and Aβ42 levels were significantly decreased in both cortex and hippocampus of active transgenics, suggesting that this may have played a role in the cognitive improvement in APP/PSEN1 mice. β-secretase was significantly reduced in active APP/PSEN1 mice compared to sedentary controls, suggesting a mechanism for reduced Aβ. Taken together, these data illustrate that exercise improves memory in wild-type and APP-overexpressing mice in fundamentally different ways.
    Neurobiology of Disease 03/2015; 78:45-55. · 5.08 Impact Factor
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    • ", 2010 ; Ma et al . , 2009 ) seemed to elicit greater benefits than either alone on behavior and Ab deposition in the Tg2576 mouse . However , not all dietary combinations have proven beneficial . Coadministration of vitamins E and C to APP / PS1 mice resulted in spatial memory impairments that were not seen when vitamin C was administered alone ( Harrison et al . , 2009 ) . In a similar mouse model , combining DHA with phospholipid precursors exacerbated Ab deposition compared with either separately whereas coadministering both these com - pounds with additional micronutrients produced an anti - amyloidogenic effect ( Broersen et al . , 2013 ) . Combining DHA with a high saturated fat mixture appeared "
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    ABSTRACT: Food combinations have been associated with lower incidence of Alzheimer’s disease (AD). We hypothesized that a combination whole-food diet (WFD) containing freeze-dried fish, vegetables and fruits would improve cognitive function in TgCRND8 mice by modulating brain insulin-signaling and neuroinflammation. Cognitive function was assessed by a comprehensive battery of tasks adapted to the Morris water maze. Unexpectedly, a ‘Diet x Transgene’ interaction was observed in which transgenic animals fed the WFD exhibited even worse cognitive function than their transgenic counterparts fed the control diet on tests of spatial memory (P<0.01) and strategic rule learning (P=0.034). These behavioural deficits coincided with higher hippocampal gene expression of tumor necrosis factor-α (P=0.013). There were no differences in cortical amyloid-β peptide species according to diet. These results indicate that a dietary profile identified from epidemiological studies exacerbated cognitive dysfunction and neuroinflammation in a mouse model of familial AD. We suggest that normally adaptive cellular responses to dietary phytochemicals were impaired by amyloid-beta deposition leading to increased oxidative stress, neuroinflammation, and behavioural deficits.
    Neurobiology of Aging 08/2014; 36(1). DOI:10.1016/j.neurobiolaging.2014.08.013 · 5.01 Impact Factor
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    • "An animal model has shown that extracts of Ocimum basilicum extract can improve memory and also have antioxidant effects [39]. Other constituents of SuperUlam with known antioxidant potential include Polygonum minus (kesum) [40], Cosmos caudatus (ulam raja), traditionally used to improve blood circulation, [11] and vitamins C and E [23, 25, 26, 41]. "
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    ABSTRACT: Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35-65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P < 0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P < 0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood.
    Evidence-based Complementary and Alternative Medicine 11/2013; 2013(2):238454. DOI:10.1155/2013/238454 · 1.88 Impact Factor
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