The Experts below are selected from a list of 4728 Experts worldwide ranked by ideXlab platform
Elizabeth Head - One of the best experts on this subject based on the ideXlab platform.
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synergistic effects of long term antioxidant diet and Behavioral Enrichment on β amyloid load and non amyloidogenic processing in aged canines
The Journal of Neuroscience, 2010Co-Authors: Viorela Pop, Elizabeth Head, B.a. Muggenburg, Norton W Milgram, Paul M Murphy, Maryann Hill, Daniel L Gillen, Nicole C Berchtold, Carl W. CotmanAbstract: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 β-amyloid (Aβ) neuropathology, as one mechanism mediating observed functional improvements. Measures assessed were Aβ neuropathology in plaques, biochemically extractable Aβ 40 and Aβ 42 species, soluble oligomeric forms of Aβ, and various proteins in the β-amyloid precursor protein (APP) processing pathway. The strongest and most consistent effects on Aβ pathology were observed in animals receiving the combined antioxidant and Enrichment treatment. Specifically, Aβ plaque load was significantly decreased in several brain regions, soluble Aβ 42 was decreased selectively in the frontal cortex, and a trend for lower Aβ oligomer levels was found in the parietal cortex. Reductions in Aβ may be related to shifted APP processing toward the non-amyloidogenic pathway, because α-secretase enzymatic activity was increased in the absence of changes in β-secretase activity. Although Enrichment alone had no significant effects on Aβ, reduced Aβ load and plaque maturation occurred in animals receiving antioxidants as a component of treatment. Aβ measures did not correlate with cognitive performance on any of the six tasks assessed, suggesting that modulation of Aβ 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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bdnf increases with Behavioral Enrichment and an antioxidant diet in the aged dog
Journal of Veterinary Behavior-clinical Applications and Research, 2010Co-Authors: Margaret Fahnestock, William N Milgram, Elizabeth Head, Viorela Pop, Monica Marchese, Bernadeta Michalski, Carl W. CotmanAbstract:The aged canine (dog) is an excellent model for investigating the neurobiological changes that underlie cognitive impairment and neurodegeneration in humans, as canines and humans undergo similar pathological and Behavioral changes with aging. Recent evidence indicates that a combination of environmental Enrichment and antioxidant-fortified diet can be used to reduce the rate of age-dependent neuropathology and cognitive decline in aged dogs, although the mechanisms underlying these changes have not been established. We examined the hypothesis that an increase in levels of brain-derived neurotrophic factor (BDNF) is one of the factors underlying improvements in learning and memory. Old, cognitively impaired animals that did not receive any treatment showed a significant decrease in BDNF mRNA in the temporal cortex when compared with the young group. Animals receiving either an antioxidant diet or environmental Enrichment displayed intermediate levels of BDNF mRNA. However, dogs receiving both an antioxidant diet and environmental Enrichment showed increased levels of BDNF mRNA when compared with untreated aged dogs, approaching levels measured in young animals. BDNF receptor TrkB mRNA levels did not differ between groups. BDNF mRNA levels were positively correlated with improved cognitive performance and inversely correlated with cortical Aβ((1-42)) and Aβ((1-40)) levels. These findings suggest that environmental Enrichment and antioxidant diet interact to maintain brain levels of BDNF, which may lead to improved cognitive performance. This is the first demonstration in a higher animal that nonpharmacological changes in lifestyle in advanced age can upregulate BDNF to levels approaching those in the young brain.
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antioxidants combined with Behavioral Enrichment can slow brain aging
2010Co-Authors: Elizabeth HeadAbstract: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.
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effects of age dietary and Behavioral Enrichment on brain mitochondria in a canine model of human aging
Experimental Neurology, 2009Co-Authors: Elizabeth Head, Carl W. Cotman, B.a. Muggenburg, Vidya N Nukala, K A Fenoglio, Patrick G SullivanAbstract:Dogs develop cognitive decline and a progressive accumulation of oxidative damage. In a previous longitudinal study, we demonstrated that aged dogs treated with either an antioxidant diet or with Behavioral Enrichment show cognitive improvement. The antioxidant diet included cellular antioxidants (vitamins E and C, fruits and vegetables) and mitochondrial cofactors (lipoic acid and carnitine). Behavioral Enrichment consisted of physical exercise, social Enrichment, and cognitive training. We hypothesized that the antioxidant treatment improved neuronal function through increased mitochondrial function. Thus, we measured reactive oxygen species (ROS) production and bioenergetics in mitochondria isolated from young, aged, and treated aged animals. Aged canine brain mitochondria show significant increases in ROS production and a reduction in NADH-linked respiration. Mitochondrial function (ROS and NADH-linked respiration) was improved selectively in aged dogs treated with an antioxidant diet. In contrast, Behavioral Enrichment had no effect on any mitochondrial parameters. These results suggest that an antioxidant diet improves cognition by maintaining mitochondrial homeostasis, which may be an independent molecular pathway not engaged by Behavioral Enrichment.
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Strategies for improving cognition with aging: insights from a longitudinal study of antioxidant and Behavioral Enrichment in canines
AGE, 2009Co-Authors: Lori-ann Christie, Wycliffe O Opii, Elizabeth HeadAbstract:Studies in humans suggest that lifestyle factors can have a beneficial impact on the risk for developing cognitive decline and dementia with age. There is growing evidence that maintaining a physically and intellectually active lifestyle can positively impact cognitive ability in older individuals. Dietary factors, such as the intake of antioxidants, may also prevent age-related cognitive decline. However, studies in humans are challenging; many variables cannot be controlled, making it difficult for researchers to determine the exact types and quantities of Enrichment and dietary factors necessary for positive effects on cognition. Studies in animal models of human aging allow researchers to precisely control such variables, and can be used to assess the mechanisms and molecular pathways underlying any positive effects. Here we review the results of an intervention study using a canine model of human aging. The study was unique in that it compared the effects of dietary antioxidant supplementation alone and in combination with Behavioral Enrichment. We found that both interventions lead to improvements in cognitive ability in aged dogs; however, combining the treatments preserved cognition to a greater extent than either treatment alone. Overall, the results suggest that antioxidant supplementation and Behavioral Enrichment target separate yet complementary molecular pathways to improve cognition, and support the idea that combinations of treatments to improve cognition and slow brain aging will produce greater benefits than single interventions.
Carl W. Cotman - One of the best experts on this subject based on the ideXlab platform.
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effects of diet and Behavioral Enrichment on free fatty acids in the aged canine brain
Neuroscience, 2012Co-Authors: Shikha Snigdha, Giuseppe Astarita, Daniele Piomelli, Carl W. CotmanAbstract:Despite several recent studies suggesting that dysregulation of brain lipid metabolism might contribute to the mechanisms of aging and Alzheimer's disease (AD), lipid metabolism has not been evaluated extensively in the aging brain. Here, we use a lipidomic approach to demonstrate that antioxidants plus mitochondrial cofactors treatment, either alone or in combination with Behavioral Enrichment, attenuates lipid abnormalities in the frontal cortices of aged canine in a manner correlated with cognitive scores. Our analyses revealed that the levels of free palmitoleic acid and nervonic acid were decreased in frontal cortices of aged dogs (n=5-6/group) treated with antioxidant compared with the control group. The monounsaturated/saturated fatty acid ratio, also known as "desaturation index"-an ex-vivo indicator of stearoyl-CoA desaturase activity, was also reduced in the frontal cortex of dogs treated with antioxidants compared with control groups. Increased palmitoleic acid levels and desaturation index were positively correlated with increased reversal learning errors and decreased cognitive performance. In conclusion, our study indicates that the addition of antioxidants and mitochondrial cofactors to the regular diet alters the composition of free fatty acids in the aged brain. Together with data showing increased palmitoleic acid levels in AD patients, our data suggest that reducing palmitoleic acid levels and desaturation index in the brain may be associated with improved cognitive performance.
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synergistic effects of long term antioxidant diet and Behavioral Enrichment on β amyloid load and non amyloidogenic processing in aged canines
The Journal of Neuroscience, 2010Co-Authors: Viorela Pop, Elizabeth Head, B.a. Muggenburg, Norton W Milgram, Paul M Murphy, Maryann Hill, Daniel L Gillen, Nicole C Berchtold, Carl W. CotmanAbstract: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 β-amyloid (Aβ) neuropathology, as one mechanism mediating observed functional improvements. Measures assessed were Aβ neuropathology in plaques, biochemically extractable Aβ 40 and Aβ 42 species, soluble oligomeric forms of Aβ, and various proteins in the β-amyloid precursor protein (APP) processing pathway. The strongest and most consistent effects on Aβ pathology were observed in animals receiving the combined antioxidant and Enrichment treatment. Specifically, Aβ plaque load was significantly decreased in several brain regions, soluble Aβ 42 was decreased selectively in the frontal cortex, and a trend for lower Aβ oligomer levels was found in the parietal cortex. Reductions in Aβ may be related to shifted APP processing toward the non-amyloidogenic pathway, because α-secretase enzymatic activity was increased in the absence of changes in β-secretase activity. Although Enrichment alone had no significant effects on Aβ, reduced Aβ load and plaque maturation occurred in animals receiving antioxidants as a component of treatment. Aβ measures did not correlate with cognitive performance on any of the six tasks assessed, suggesting that modulation of Aβ 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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bdnf increases with Behavioral Enrichment and an antioxidant diet in the aged dog
Journal of Veterinary Behavior-clinical Applications and Research, 2010Co-Authors: Margaret Fahnestock, William N Milgram, Elizabeth Head, Viorela Pop, Monica Marchese, Bernadeta Michalski, Carl W. CotmanAbstract:The aged canine (dog) is an excellent model for investigating the neurobiological changes that underlie cognitive impairment and neurodegeneration in humans, as canines and humans undergo similar pathological and Behavioral changes with aging. Recent evidence indicates that a combination of environmental Enrichment and antioxidant-fortified diet can be used to reduce the rate of age-dependent neuropathology and cognitive decline in aged dogs, although the mechanisms underlying these changes have not been established. We examined the hypothesis that an increase in levels of brain-derived neurotrophic factor (BDNF) is one of the factors underlying improvements in learning and memory. Old, cognitively impaired animals that did not receive any treatment showed a significant decrease in BDNF mRNA in the temporal cortex when compared with the young group. Animals receiving either an antioxidant diet or environmental Enrichment displayed intermediate levels of BDNF mRNA. However, dogs receiving both an antioxidant diet and environmental Enrichment showed increased levels of BDNF mRNA when compared with untreated aged dogs, approaching levels measured in young animals. BDNF receptor TrkB mRNA levels did not differ between groups. BDNF mRNA levels were positively correlated with improved cognitive performance and inversely correlated with cortical Aβ((1-42)) and Aβ((1-40)) levels. These findings suggest that environmental Enrichment and antioxidant diet interact to maintain brain levels of BDNF, which may lead to improved cognitive performance. This is the first demonstration in a higher animal that nonpharmacological changes in lifestyle in advanced age can upregulate BDNF to levels approaching those in the young brain.
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effects of age dietary and Behavioral Enrichment on brain mitochondria in a canine model of human aging
Experimental Neurology, 2009Co-Authors: Elizabeth Head, Carl W. Cotman, B.a. Muggenburg, Vidya N Nukala, K A Fenoglio, Patrick G SullivanAbstract:Dogs develop cognitive decline and a progressive accumulation of oxidative damage. In a previous longitudinal study, we demonstrated that aged dogs treated with either an antioxidant diet or with Behavioral Enrichment show cognitive improvement. The antioxidant diet included cellular antioxidants (vitamins E and C, fruits and vegetables) and mitochondrial cofactors (lipoic acid and carnitine). Behavioral Enrichment consisted of physical exercise, social Enrichment, and cognitive training. We hypothesized that the antioxidant treatment improved neuronal function through increased mitochondrial function. Thus, we measured reactive oxygen species (ROS) production and bioenergetics in mitochondria isolated from young, aged, and treated aged animals. Aged canine brain mitochondria show significant increases in ROS production and a reduction in NADH-linked respiration. Mitochondrial function (ROS and NADH-linked respiration) was improved selectively in aged dogs treated with an antioxidant diet. In contrast, Behavioral Enrichment had no effect on any mitochondrial parameters. These results suggest that an antioxidant diet improves cognition by maintaining mitochondrial homeostasis, which may be an independent molecular pathway not engaged by Behavioral Enrichment.
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proteomic identification of brain proteins in the canine model of human aging following a long term treatment with antioxidants and a program of Behavioral Enrichment relevance to alzheimer s disease
Neurobiology of Aging, 2008Co-Authors: Wycliffe O Opii, Gururaj Joshi, William N Milgram, William M Pierce, Elizabeth Head, Carl W. Cotman, B.a. Muggenburg, Jon B Klein, Allan D ButterfieldAbstract:Aging and age-related disorders such as Alzheimer’s disease (AD) are usually accompanied by oxidative stress as one of the main mechanisms contributing to neurodegeneration and cognitive decline. Aging canines develop cognitive dysfunction and neuropathology similar to those seen in humans, and the use of antioxidants results in reductions in oxidative damage and in improvement in cognitive function in this canine model of human aging. In the present study, the effect of a long-term treatment with an antioxidant fortified diet and a program of Behavioral Enrichment on oxidative damage was studied in aged canines. To identify the neurobiological mechanisms underlying these treatment effects, the parietal cortex from 23 beagle dogs (8.1-12.4 years) were treated for 2.8 years in one of four treatment groups: i.e., control food- control Behavioral Enrichment (CC); control food - Behavioral Enrichment (CE); antioxidant food-control Behavioral Enrichment (CA); and enriched environment - antioxidant fortified food (EA). We analyzed the levels of the oxidative stress biomarkers, i.e., protein carbonyls, 3-nitrotyroine (3NT), and the lipid peroxidation product, 4-hydroxynonenal (HNE), and observed a decrease in their levels on all treatments when compared to control, with the most significant effects found in the combined treatment, EA. Since EA treatment was most effective, we also carried out a comparative proteomics study to identify specific brain proteins that were differentially expressed and used a parallel redox proteomics approach to identify specific brain proteins that were less oxidized following EA. The specific protein carbonyl levels of glutamate dehydrogenase [NAD (P)], glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α-enolase, neurofilament triplet L protein, glutathione S-transferase (GST) and fascin actin bundling protein were significantly reduced in brain of EA-treated dogs compared to control. We also observed significant increases in expression of Cu/Zn superoxide dismutase, fructose-bisphosphate aldolase C, creatine kinase, glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The increased expression of these proteins and in particular Cu/Zn SOD correlated with improved cognitive function. In addition, there was a significant increase in the enzymatic activities of glutathione-S-transferase (GST) and total superoxide dismutase (SOD), and significant increase in the protein levels of heme oxygenase (HO-1) in EA treated dogs compared to control. These findings suggest that the combined treatment reduces the levels of oxidative damage and improves the antioxidant reserve systems in the aging canine brain, and may contribute to improvements in learning and memory. These observations provide insights into a possible neurobiological mechanism underlying the effects of the combined treatment. These results support the combination treatments as a possible therapeutic approach that could be translated to the aging human population who are at risk for age-related neurodegenerative disorders, including Alzheimer’s disease.
B.a. Muggenburg - One of the best experts on this subject based on the ideXlab platform.
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synergistic effects of long term antioxidant diet and Behavioral Enrichment on β amyloid load and non amyloidogenic processing in aged canines
The Journal of Neuroscience, 2010Co-Authors: Viorela Pop, Elizabeth Head, B.a. Muggenburg, Norton W Milgram, Paul M Murphy, Maryann Hill, Daniel L Gillen, Nicole C Berchtold, Carl W. CotmanAbstract: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 β-amyloid (Aβ) neuropathology, as one mechanism mediating observed functional improvements. Measures assessed were Aβ neuropathology in plaques, biochemically extractable Aβ 40 and Aβ 42 species, soluble oligomeric forms of Aβ, and various proteins in the β-amyloid precursor protein (APP) processing pathway. The strongest and most consistent effects on Aβ pathology were observed in animals receiving the combined antioxidant and Enrichment treatment. Specifically, Aβ plaque load was significantly decreased in several brain regions, soluble Aβ 42 was decreased selectively in the frontal cortex, and a trend for lower Aβ oligomer levels was found in the parietal cortex. Reductions in Aβ may be related to shifted APP processing toward the non-amyloidogenic pathway, because α-secretase enzymatic activity was increased in the absence of changes in β-secretase activity. Although Enrichment alone had no significant effects on Aβ, reduced Aβ load and plaque maturation occurred in animals receiving antioxidants as a component of treatment. Aβ measures did not correlate with cognitive performance on any of the six tasks assessed, suggesting that modulation of Aβ 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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effects of age dietary and Behavioral Enrichment on brain mitochondria in a canine model of human aging
Experimental Neurology, 2009Co-Authors: Elizabeth Head, Carl W. Cotman, B.a. Muggenburg, Vidya N Nukala, K A Fenoglio, Patrick G SullivanAbstract:Dogs develop cognitive decline and a progressive accumulation of oxidative damage. In a previous longitudinal study, we demonstrated that aged dogs treated with either an antioxidant diet or with Behavioral Enrichment show cognitive improvement. The antioxidant diet included cellular antioxidants (vitamins E and C, fruits and vegetables) and mitochondrial cofactors (lipoic acid and carnitine). Behavioral Enrichment consisted of physical exercise, social Enrichment, and cognitive training. We hypothesized that the antioxidant treatment improved neuronal function through increased mitochondrial function. Thus, we measured reactive oxygen species (ROS) production and bioenergetics in mitochondria isolated from young, aged, and treated aged animals. Aged canine brain mitochondria show significant increases in ROS production and a reduction in NADH-linked respiration. Mitochondrial function (ROS and NADH-linked respiration) was improved selectively in aged dogs treated with an antioxidant diet. In contrast, Behavioral Enrichment had no effect on any mitochondrial parameters. These results suggest that an antioxidant diet improves cognition by maintaining mitochondrial homeostasis, which may be an independent molecular pathway not engaged by Behavioral Enrichment.
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proteomic identification of brain proteins in the canine model of human aging following a long term treatment with antioxidants and a program of Behavioral Enrichment relevance to alzheimer s disease
Neurobiology of Aging, 2008Co-Authors: Wycliffe O Opii, Gururaj Joshi, William N Milgram, William M Pierce, Elizabeth Head, Carl W. Cotman, B.a. Muggenburg, Jon B Klein, Allan D ButterfieldAbstract:Aging and age-related disorders such as Alzheimer’s disease (AD) are usually accompanied by oxidative stress as one of the main mechanisms contributing to neurodegeneration and cognitive decline. Aging canines develop cognitive dysfunction and neuropathology similar to those seen in humans, and the use of antioxidants results in reductions in oxidative damage and in improvement in cognitive function in this canine model of human aging. In the present study, the effect of a long-term treatment with an antioxidant fortified diet and a program of Behavioral Enrichment on oxidative damage was studied in aged canines. To identify the neurobiological mechanisms underlying these treatment effects, the parietal cortex from 23 beagle dogs (8.1-12.4 years) were treated for 2.8 years in one of four treatment groups: i.e., control food- control Behavioral Enrichment (CC); control food - Behavioral Enrichment (CE); antioxidant food-control Behavioral Enrichment (CA); and enriched environment - antioxidant fortified food (EA). We analyzed the levels of the oxidative stress biomarkers, i.e., protein carbonyls, 3-nitrotyroine (3NT), and the lipid peroxidation product, 4-hydroxynonenal (HNE), and observed a decrease in their levels on all treatments when compared to control, with the most significant effects found in the combined treatment, EA. Since EA treatment was most effective, we also carried out a comparative proteomics study to identify specific brain proteins that were differentially expressed and used a parallel redox proteomics approach to identify specific brain proteins that were less oxidized following EA. The specific protein carbonyl levels of glutamate dehydrogenase [NAD (P)], glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α-enolase, neurofilament triplet L protein, glutathione S-transferase (GST) and fascin actin bundling protein were significantly reduced in brain of EA-treated dogs compared to control. We also observed significant increases in expression of Cu/Zn superoxide dismutase, fructose-bisphosphate aldolase C, creatine kinase, glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The increased expression of these proteins and in particular Cu/Zn SOD correlated with improved cognitive function. In addition, there was a significant increase in the enzymatic activities of glutathione-S-transferase (GST) and total superoxide dismutase (SOD), and significant increase in the protein levels of heme oxygenase (HO-1) in EA treated dogs compared to control. These findings suggest that the combined treatment reduces the levels of oxidative damage and improves the antioxidant reserve systems in the aging canine brain, and may contribute to improvements in learning and memory. These observations provide insights into a possible neurobiological mechanism underlying the effects of the combined treatment. These results support the combination treatments as a possible therapeutic approach that could be translated to the aging human population who are at risk for age-related neurodegenerative disorders, including Alzheimer’s disease.
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learning ability in aged beagle dogs is preserved by Behavioral Enrichment and dietary fortification a two year longitudinal study
Neurobiology of Aging, 2004Co-Authors: Norton W Milgram, Elizabeth Head, B.a. Muggenburg, Candace J Ikedadouglas, Steven C Zicker, Heather Murphey, Christina T Siwak, Dwight Tapp, Carl W. CotmanAbstract:The effectiveness of two interventions, dietary fortification with antioxidants and a program of Behavioral Enrichment, was assessed in a longitudinal study of cognitive aging in beagle dogs. A baseline protocol of cognitive testing was used to select four cognitively equivalent groups: control food-control experience (C-C), control food-enriched experience (C-E), antioxidant fortified food-control experience (A-C), and antioxidant fortified food-enriched experience(A-E). We also included two groups of young Behaviorally enriched dogs, one receiving the control food and the other the fortified food. Discrimination learning and reversal was assessed after one year of treatment with a size discrimination task, and again after two years with a black/white discrimination task. The four aged groups were comparable at baseline. At one and two years, the aged combined treatment group showed more accurate learning than the other aged groups. Discrimination learning was significantly improved by Behavioral Enrichment. Reversal learning was improved by both Behavioral Enrichment and dietary fortification. By contrast, the fortified food had no effect on the young dogs. These results suggest that Behavioral Enrichment or dietary fortification with antioxidants over a long-duration can slow age-dependent cognitive decline, and that the two treatments together are more effective than either alone in older dogs.
Wycliffe O Opii - One of the best experts on this subject based on the ideXlab platform.
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Strategies for improving cognition with aging: insights from a longitudinal study of antioxidant and Behavioral Enrichment in canines
AGE, 2009Co-Authors: Lori-ann Christie, Wycliffe O Opii, Elizabeth HeadAbstract:Studies in humans suggest that lifestyle factors can have a beneficial impact on the risk for developing cognitive decline and dementia with age. There is growing evidence that maintaining a physically and intellectually active lifestyle can positively impact cognitive ability in older individuals. Dietary factors, such as the intake of antioxidants, may also prevent age-related cognitive decline. However, studies in humans are challenging; many variables cannot be controlled, making it difficult for researchers to determine the exact types and quantities of Enrichment and dietary factors necessary for positive effects on cognition. Studies in animal models of human aging allow researchers to precisely control such variables, and can be used to assess the mechanisms and molecular pathways underlying any positive effects. Here we review the results of an intervention study using a canine model of human aging. The study was unique in that it compared the effects of dietary antioxidant supplementation alone and in combination with Behavioral Enrichment. We found that both interventions lead to improvements in cognitive ability in aged dogs; however, combining the treatments preserved cognition to a greater extent than either treatment alone. Overall, the results suggest that antioxidant supplementation and Behavioral Enrichment target separate yet complementary molecular pathways to improve cognition, and support the idea that combinations of treatments to improve cognition and slow brain aging will produce greater benefits than single interventions.
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proteomic identification of brain proteins in the canine model of human aging following a long term treatment with antioxidants and a program of Behavioral Enrichment relevance to alzheimer s disease
Neurobiology of Aging, 2008Co-Authors: Wycliffe O Opii, Gururaj Joshi, William N Milgram, William M Pierce, Elizabeth Head, Carl W. Cotman, B.a. Muggenburg, Jon B Klein, Allan D ButterfieldAbstract:Aging and age-related disorders such as Alzheimer’s disease (AD) are usually accompanied by oxidative stress as one of the main mechanisms contributing to neurodegeneration and cognitive decline. Aging canines develop cognitive dysfunction and neuropathology similar to those seen in humans, and the use of antioxidants results in reductions in oxidative damage and in improvement in cognitive function in this canine model of human aging. In the present study, the effect of a long-term treatment with an antioxidant fortified diet and a program of Behavioral Enrichment on oxidative damage was studied in aged canines. To identify the neurobiological mechanisms underlying these treatment effects, the parietal cortex from 23 beagle dogs (8.1-12.4 years) were treated for 2.8 years in one of four treatment groups: i.e., control food- control Behavioral Enrichment (CC); control food - Behavioral Enrichment (CE); antioxidant food-control Behavioral Enrichment (CA); and enriched environment - antioxidant fortified food (EA). We analyzed the levels of the oxidative stress biomarkers, i.e., protein carbonyls, 3-nitrotyroine (3NT), and the lipid peroxidation product, 4-hydroxynonenal (HNE), and observed a decrease in their levels on all treatments when compared to control, with the most significant effects found in the combined treatment, EA. Since EA treatment was most effective, we also carried out a comparative proteomics study to identify specific brain proteins that were differentially expressed and used a parallel redox proteomics approach to identify specific brain proteins that were less oxidized following EA. The specific protein carbonyl levels of glutamate dehydrogenase [NAD (P)], glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α-enolase, neurofilament triplet L protein, glutathione S-transferase (GST) and fascin actin bundling protein were significantly reduced in brain of EA-treated dogs compared to control. We also observed significant increases in expression of Cu/Zn superoxide dismutase, fructose-bisphosphate aldolase C, creatine kinase, glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The increased expression of these proteins and in particular Cu/Zn SOD correlated with improved cognitive function. In addition, there was a significant increase in the enzymatic activities of glutathione-S-transferase (GST) and total superoxide dismutase (SOD), and significant increase in the protein levels of heme oxygenase (HO-1) in EA treated dogs compared to control. These findings suggest that the combined treatment reduces the levels of oxidative damage and improves the antioxidant reserve systems in the aging canine brain, and may contribute to improvements in learning and memory. These observations provide insights into a possible neurobiological mechanism underlying the effects of the combined treatment. These results support the combination treatments as a possible therapeutic approach that could be translated to the aging human population who are at risk for age-related neurodegenerative disorders, including Alzheimer’s disease.
Norton W Milgram - One of the best experts on this subject based on the ideXlab platform.
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synergistic effects of long term antioxidant diet and Behavioral Enrichment on β amyloid load and non amyloidogenic processing in aged canines
The Journal of Neuroscience, 2010Co-Authors: Viorela Pop, Elizabeth Head, B.a. Muggenburg, Norton W Milgram, Paul M Murphy, Maryann Hill, Daniel L Gillen, Nicole C Berchtold, Carl W. CotmanAbstract: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 β-amyloid (Aβ) neuropathology, as one mechanism mediating observed functional improvements. Measures assessed were Aβ neuropathology in plaques, biochemically extractable Aβ 40 and Aβ 42 species, soluble oligomeric forms of Aβ, and various proteins in the β-amyloid precursor protein (APP) processing pathway. The strongest and most consistent effects on Aβ pathology were observed in animals receiving the combined antioxidant and Enrichment treatment. Specifically, Aβ plaque load was significantly decreased in several brain regions, soluble Aβ 42 was decreased selectively in the frontal cortex, and a trend for lower Aβ oligomer levels was found in the parietal cortex. Reductions in Aβ may be related to shifted APP processing toward the non-amyloidogenic pathway, because α-secretase enzymatic activity was increased in the absence of changes in β-secretase activity. Although Enrichment alone had no significant effects on Aβ, reduced Aβ load and plaque maturation occurred in animals receiving antioxidants as a component of treatment. Aβ measures did not correlate with cognitive performance on any of the six tasks assessed, suggesting that modulation of Aβ 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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learning ability in aged beagle dogs is preserved by Behavioral Enrichment and dietary fortification a two year longitudinal study
Neurobiology of Aging, 2004Co-Authors: Norton W Milgram, Elizabeth Head, B.a. Muggenburg, Candace J Ikedadouglas, Steven C Zicker, Heather Murphey, Christina T Siwak, Dwight Tapp, Carl W. CotmanAbstract:The effectiveness of two interventions, dietary fortification with antioxidants and a program of Behavioral Enrichment, was assessed in a longitudinal study of cognitive aging in beagle dogs. A baseline protocol of cognitive testing was used to select four cognitively equivalent groups: control food-control experience (C-C), control food-enriched experience (C-E), antioxidant fortified food-control experience (A-C), and antioxidant fortified food-enriched experience(A-E). We also included two groups of young Behaviorally enriched dogs, one receiving the control food and the other the fortified food. Discrimination learning and reversal was assessed after one year of treatment with a size discrimination task, and again after two years with a black/white discrimination task. The four aged groups were comparable at baseline. At one and two years, the aged combined treatment group showed more accurate learning than the other aged groups. Discrimination learning was significantly improved by Behavioral Enrichment. Reversal learning was improved by both Behavioral Enrichment and dietary fortification. By contrast, the fortified food had no effect on the young dogs. These results suggest that Behavioral Enrichment or dietary fortification with antioxidants over a long-duration can slow age-dependent cognitive decline, and that the two treatments together are more effective than either alone in older dogs.
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long term treatment with antioxidants and a program of Behavioral Enrichment reduces age dependent impairment in discrimination and reversal learning in beagle dogs
Experimental Gerontology, 2004Co-Authors: Norton W Milgram, Elizabeth Head, Candace J Ikedadouglas, Steven C Zicker, Heather Murphey, Christina T Siwak, Bruce A Muggenberg, Dwight P Tapp, Stephen R Lowry, Carl W. CotmanAbstract:Abstract The effects of long-term treatment with both antioxidants and a program of Behavioral Enrichment were studied as part of a longitudinal investigation of cognitive aging in beagle dogs. Baseline performance on a battery of cognitive tests was used to assign 48 aged dogs (9–12 years) into four cognitively equivalent groups, of 12 animals per group: Group CC (control food–control environment), group CE (control food–enriched environment); Group AC (antioxidant fortified food–control environment); Group AE (fortified food–enriched environment). We also tested a group of young dogs fed the control food and a second group fed the fortified food. Both groups of young dogs received a program of Behavioral Enrichment. To evaluate the effects of the interventions on cognition after 1 year, the dogs were tested on a size discrimination learning task and subsequently on a size discrimination reversal learning task. Both tasks showed age-sensitivity, with old dogs performing more poorly than young dogs. Both tasks were also improved by both the fortified food and the Behavioral Enrichment. However, in both instances the treatment effects largely reflected improved performance in the combined treatment group. These results suggest that the effectiveness of antioxidants in attenuating age-dependent cognitive decline is dependent on Behavioral and environmental experience.