Synergistic Effects of Long-Term Antioxidant Diet and Behavioral Enrichment on beta-Amyloid Load and Non-Amyloidogenic Processing in Aged Canines
ABSTRACT A long-term intervention (2.69 years) with an antioxidant diet, behavioral enrichment, or the combined treatment preserved and improved cognitive function in aged canines. Although each intervention alone provided cognitive benefits, the combination treatment was additive. We evaluate the hypothesis that antioxidants, enrichment, or the combination intervention reduces age-related beta-amyloid (Abeta) neuropathology, as one mechanism mediating observed functional improvements. Measures assessed were Abeta neuropathology in plaques, biochemically extractable Abeta(40) and Abeta(42) species, soluble oligomeric forms of Abeta, and various proteins in the beta-amyloid precursor protein (APP) processing pathway. The strongest and most consistent effects on Abeta pathology were observed in animals receiving the combined antioxidant and enrichment treatment. Specifically, Abeta plaque load was significantly decreased in several brain regions, soluble Abeta(42) was decreased selectively in the frontal cortex, and a trend for lower Abeta oligomer levels was found in the parietal cortex. Reductions in Abeta may be related to shifted APP processing toward the non-amyloidogenic pathway, because alpha-secretase enzymatic activity was increased in the absence of changes in beta-secretase activity. Although enrichment alone had no significant effects on Abeta, reduced Abeta load and plaque maturation occurred in animals receiving antioxidants as a component of treatment. Abeta measures did not correlate with cognitive performance on any of the six tasks assessed, suggesting that modulation of Abeta alone may be a relatively minor mechanism mediating cognitive benefits of the interventions. Overall, the data indicate that multidomain treatments may be a valuable intervention strategy to reduce neuropathology and improve cognitive function in humans.
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- "For example, small bouts of environmental enrichment have important genetic effects on developing mice (Arai & Feig 2010). In addition, behavioral enrichment decreases β-amyloid load in several brain regions of aging laboratory beagle dogs and protects against cognitive decline associated with aging (Christie et al. 2009; Cotman & Head 2008; Pop et al. 2010). In considering the possible implications of these results for the human case, however, it is not clear to what extent these findings may be a product of the deprived conditions offered by the laboratory. "
ABSTRACT: We review a range of studies on the genetic contribution to behavior in canid species. We begin by identifying factors that make canids a promising model in behavioral genetics and proceed to review research over the last decade that has used canids to identify genetic contributions to behavior. We first review studies that have selectively bred dogs to identify genetic contributions to behavior and then review studies that estimate heritability from populations of non-laboratory bred dogs. We subsequently review studies that used molecular genetics to identify gene-behavior associations and note associations that have been uncovered. We then note challenges in canid behavioral genetics research that require further consideration. We finish by suggesting alternative phenotyping methods and identify areas in which canids may have as yet unexploited advantages, such as in gene-environment interaction studies where genetic factors are found to moderate the effects of environmental variables.Genes Brain and Behavior 09/2012; 11(8). DOI:10.1111/j.1601-183X.2012.00851.x · 3.51 Impact Factor
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ABSTRACT: Three approaches to the teaching of English for Academic Purposes (EAP) are identified, the Critical approach, the Pragmatic approach, and the Critical Pragmatic approach. Critical EAP is appealing pedagogically because of its restive questioning of discourse norms, although it can seem reactionary at times. By focusing on the acquisition of the same dominant norms, Pragmatic EAP has a clear goal, but it often fails to acknowledge difference in community practices. Critical Pragmatism fuses Critical EAP's focus on difference in the academy with Pragmatic EAP's focus on access to the academy. The Critical Pragmatic approach is illustrated by activities for postgraduate and research students which centre on the use of personal pronouns and possessive adjectives.English for Specific Purposes 01/2004; 23(4-23):355-377. DOI:10.1016/j.esp.2003.08.001 · 1.28 Impact Factor
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ABSTRACT: In the brain, oxidative damage, loss of synapses, and loss of growth factors such as brain-derived neurotrophic factor (BDNF) are linked to age-associated cognitive decline and Alzheimer’s disease (AD). Antioxidant treatments to reduce oxidative damage have provided only modest benefits in human clinical trials. Cognitive and physical training, which may promote synapse growth and maintenance and increase BDNF, has proved to be more promising in small clinical trials in normal aged individuals and AD patients. Using a canine model of human brain aging, which naturally accumulates oxidative damage and cognitive dysfunction, we tested the hypothesis that combining treatments that can reduce several age-associated neuropathologies will prove to be more efficacious than targeting a single pathologic cascade. Aged beagles were either fed an antioxidant/mitochondrial cofactor diet (vitamins E and C, fruits and vegetables, lipoic acid and carnitine) or provided with behavioral enrichment that can increase BDNF and synapse and neuron growth (environmental, social, and cognitive enrichment with physical exercise) or treated with a combination of both the diet and behavioral enrichment. Cognitive improvements were observed for each treatment alone, but the combination approach, in particular, led to larger improvements in learning scores, to maintenance of cognitive ability, and to recovery of impaired memory function. Notably, each treatment selectively reduced different types of neuropathology in the brain. The use of a combination of antioxidant supplement or diet and other lifestyle modifications (increased social activity, physical activity, and cognitive engagement) may work additively and be beneficial for healthy human brain aging. KeywordsAcetyl-l-carnitine-Alzheimer’s disease-Beagle-Beta-amyloid-Dog-Canine-Lipoic acid-Oxidative damage12/2009: pages 381-397;