Compelling evidence indicates that excess consumption of sugar-sweetened beverages plays an important role in the epidemic of obesity, a major risk factor for type 2 diabetes mellitus. Type 2 diabetes mellitus has been associated with a higher incidence of Alzheimer disease (AD). High fat diets promote AD-like pathology in mice. It is not known whether consumption of excess sugar as in calorically sweetened beverages with an otherwise normal diet affects the development of AD. In the present study, we provided 10% sucrose-sweetened water to a transgenic mouse model of AD with a normal rodent diet. Compared with the control mice with no sucrose added in the water, the sucrose group gained more body weight and developed glucose intolerance, hyperinsulinemia, and hypercholesterolemia. These metabolic changes were associated with the exacerbation of memory impairment and a 2-3-fold increase in insoluble amyloid-beta protein levels and deposition in the brain. We further showed that the levels of expression and secretase-cleaved products of amyloid-beta precursor protein were not affected by sucrose intake. The steady-state levels of insulin-degrading enzyme did not change significantly, whereas there was a 2.5-fold increase in brain apoE levels. Therefore, we concluded that the up-regulation of apoE accelerated the aggregation of Abeta, resulting in the exacerbation of cerebral amyloidosis in sucrose-treated mice. These data underscore the potential role of dietary sugar in the pathogenesis of AD and suggest that controlling the consumption of sugar-sweetened beverages may be an effective way to curtail the risk of developing AD.
"ch can further hinder cerebral MRglu and cognitive function . The MWM is a classic task for assessing hippocampal - dependent spatial memory ( Bromley - Brits et al . , 2011 ) . Longer escape times during the training phase of the MWM in HFD - treated Tg 2576 mice and sucrose - treated APP / PS1 AD mice are associated with an increased Ab burden ( Cao et al . , 2007 ) . We found no difference in the escape latencies between NCD AD and HFSTZ AD mice during the training phase of the MWM , suggesting that this task is not sufficiently sensitive to detect an impact of HFSTZ treatment on the hippocampus - dependent learning and memory during the early stage of APP / PS1 mice ( Chen et al . , 2012 ) ."
"We did not conduct a cued-platform control task for several reasons. First, we and others have already shown that the APP/PSEN1 mice have robust spatial learning impairments in the water maze but are unimpaired on the non-spatial cued control task (Bernardo et al., 2007; Cao et al., 2007; Cohen et al., 2009; Harrison et al., 2009b; Harrison et al., 2010; Lewis et al., 2010). Second, the transgenics also exhibit deficits in cognitive flexibility (Arrazola et al., 2009; Reiserer et al., 2007; Toledo and Inestrosa, 2010), a putatively frontally-mediated cognitive process involved in, e.g., switching learning modalities from cued to spatial. "
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] ABSTRACT: The pronounced global rise in sugar consumption in recent years has been driven largely by increased consumption of sugar-sweetened beverages. Although high sugar intakes are recognised as increasing the risk of obesity and related metabolic disturbances, less is known about how sugar might also impair cognition and learned behaviour. This review considers the effects of sugar in rodents on measures of learning and memory; reward processing, anxiety and mood. The parallels between sugar consumption and addictive behaviours are also discussed. The available evidence clearly indicates that sugar consumption can induce cognitive dysfunction. Deficits have been found most consistently on tasks measuring spatial learning and memory. Younger animals appear to be particularly sensitive to the effects of sugar on reward processing, yet results vary according to what reward-related behaviour is assessed. Sugar does not appear to produce long-term effects on anxiety or mood. Importantly, cognitive impairments have been found when intake approximates levels of sugar consumption in people and without changes to weight gain. There remain several caveats when extrapolating from animal models to putative effects of sugar on cognitive function in people. These issues are discussed in conjunction with potential underlying neural mechanisms and directions for future research.
M Nakata, S Yamamoto, T Okada, G Darambazar, H Okano, K Ozawa, T Yada
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