The Experts below are selected from a list of 48711 Experts worldwide ranked by ideXlab platform
Anthony J. Hannan - One of the best experts on this subject based on the ideXlab platform.
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Differential effects of voluntary physical exercise on behavioral and Brain-Derived Neurotrophic Factor expression deficits in huntington’s disease transgenic mice
Neuroscience, 2006Co-Authors: Terence Y. Pang, Nathan C. Stam, Jess Nithianantharajah, Monique L. Howard, Anthony J. HannanAbstract:Huntington's disease is a fatal neurodegenerative disorder caused by a mutation of the huntingtin gene and involves progressive motor abnormalities (including chorea), cognitive deficits (dementia) as well as psychiatric symptoms. We have previously demonstrated that environmental enrichment slows the onset and progression of Huntington's disease in transgenic mice. Here, we investigated the effects of enhanced physical exercise on disease progression and Brain-Derived Neurotrophic Factor expression. Standard-housed Huntington's disease mice developed phenotypic rear-paw clasping by 16 weeks of age, displayed abnormal rearing behavior, deficits in motor co-ordination and of spatial working memory. Huntington's disease mice with access to running wheels exhibited delayed onset of rear-paw clasping, normalized levels of rearing behavior and amelioration of the cognitive deficits. However, in contrast to our previous environmental enrichment studies, there was no rescue of motor coordination deficits in wheel-running Huntington's disease mice. An abnormal accumulation of Brain-Derived Neurotrophic Factor protein in the frontal cortex of Huntington's disease mice was unaffected by running. Striatal and hippocampal Brain-Derived Neurotrophic Factor protein levels were unchanged. Brain-Derived Neurotrophic Factor mRNA levels were reduced in the anterior cortex, striatum and hippocampus of Huntington's disease mice, and only striatal deficits were ameliorated by running. Overall, we show that voluntary physical exercise delays the onset of Huntington's disease and the decline in cognitive ability. In addition, our results reveal that some aspects of hippocampal dependent memory are not entirely reliant on sustained hippocampal Brain-Derived Neurotrophic Factor expression.
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differential effects of voluntary physical exercise on behavioral and brain derived Neurotrophic Factor expression deficits in huntington s disease transgenic mice
Neuroscience, 2006Co-Authors: Terence Y. Pang, Nathan C. Stam, Jess Nithianantharajah, Monique L. Howard, Anthony J. HannanAbstract:Huntington's disease is a fatal neurodegenerative disorder caused by a mutation of the huntingtin gene and involves progressive motor abnormalities (including chorea), cognitive deficits (dementia) as well as psychiatric symptoms. We have previously demonstrated that environmental enrichment slows the onset and progression of Huntington's disease in transgenic mice. Here, we investigated the effects of enhanced physical exercise on disease progression and Brain-Derived Neurotrophic Factor expression. Standard-housed Huntington's disease mice developed phenotypic rear-paw clasping by 16 weeks of age, displayed abnormal rearing behavior, deficits in motor co-ordination and of spatial working memory. Huntington's disease mice with access to running wheels exhibited delayed onset of rear-paw clasping, normalized levels of rearing behavior and amelioration of the cognitive deficits. However, in contrast to our previous environmental enrichment studies, there was no rescue of motor coordination deficits in wheel-running Huntington's disease mice. An abnormal accumulation of Brain-Derived Neurotrophic Factor protein in the frontal cortex of Huntington's disease mice was unaffected by running. Striatal and hippocampal Brain-Derived Neurotrophic Factor protein levels were unchanged. Brain-Derived Neurotrophic Factor mRNA levels were reduced in the anterior cortex, striatum and hippocampus of Huntington's disease mice, and only striatal deficits were ameliorated by running. Overall, we show that voluntary physical exercise delays the onset of Huntington's disease and the decline in cognitive ability. In addition, our results reveal that some aspects of hippocampal dependent memory are not entirely reliant on sustained hippocampal Brain-Derived Neurotrophic Factor expression.
Helen E Scharfman - One of the best experts on this subject based on the ideXlab platform.
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brain derived Neurotrophic Factor transgenic mice exhibit passive avoidance deficits increased seizure severity and in vitro hyperexcitability in the hippocampus and entorhinal cortex
Neuroscience, 1999Co-Authors: Susan D Croll, John S. Rudge, Ronald M. Lindsay, George D. Yancopoulos, Chitra Suri, Debra L Compton, Mary V Simmons, Stanley J Wiegand, Helen E ScharfmanAbstract:Transgenic mice overexpressing Brain-Derived Neurotrophic Factor from the β-actin promoter were tested for behavioral, gross anatomical and physiological abnormalities. Brain-Derived Neurotrophic Factor messenger RNA overexpression was widespread throughout brain. Overexpression declined with age, such that levels of overexpression decreased sharply by nine months. Brain-Derived Neurotrophic Factor transgenic mice had no gross deformities or behavioral abnormalities. However, they showed a significant passive avoidance deficit. This deficit was dependent on continued overexpression, and resolved with age as Brain-Derived Neurotrophic Factor transcripts decreased. In addition, the Brain-Derived Neurotrophic Factor transgenic mice showed increased seizure severity in response to kainic acid. Hippocampal slices from Brain-Derived Neurotrophic Factor transgenic mice showed hyperexcitability in area CA3 and entorhinal cortex, but not in dentate gyrus. Finally, area CA1 long-term potentiation was disrupted, indicating abnormal plasticity. Our data suggest that overexpression of Brain-Derived Neurotrophic Factor in the brain can interfere with normal brain function by causing learning impairments and increased excitability. The results also support the hypothesis that excess Brain-Derived Neurotrophic Factor could be pro-convulsant in the limbic system.
Fernando Gomezpinilla - One of the best experts on this subject based on the ideXlab platform.
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coupling energy metabolism with a mechanism to support brain derived Neurotrophic Factor mediated synaptic plasticity
Neuroscience, 2006Co-Authors: Shoshanna Vaynman, Zhe Ying, Fernando GomezpinillaAbstract:Synaptic plasticity and behaviors are likely dependent on the capacity of neurons to meet the energy demands imposed by neuronal activity. We used physical activity, a paradigm intrinsically associated with energy consumption/expenditure and cognitive enhancement, to study how energy metabolism interacts with the substrates for neuroplasticity. We found that in an area critical for learning and memory, the hippocampus, exercise modified aspects of energy metabolism by decreasing oxidative stress and increasing the levels of cytochrome c oxidase-II, a specific component of mitochondrial machinery. We infused 1,25-dihydroxyvitamin D3, a modulator of energy metabolism, directly into the hippocampus during 3 days of voluntary wheel running and measured its effects on Brain-Derived Neurotrophic Factor-mediated synaptic plasticity. Brain-Derived Neurotrophic Factor is a central player for the effects of exercise on synaptic and cognitive plasticity. We found that 25-dihydroxyvitamin D3 decreased exercise-induced Brain-Derived Neurotrophic Factor but had no significant effect on neurotrophin-3 levels, thereby suggesting a level of specificity for Brain-Derived Neurotrophic Factor in the hippocampus. 25-Dihydroxyvitamin D3 injection also abolished the effects of exercise on the consummate end-products of Brain-Derived Neurotrophic Factor action, i.e. cyclic AMP response element-binding protein and synapsin I, and modulated phosphorylated calmodulin protein kinase II, a signal transduction cascade downstream to Brain-Derived Neurotrophic Factor action that is important for learning and memory. We also found that exercise significantly increased the expression of the mitochondrial uncoupling protein 2, an energy-balancing Factor concerned with ATP production and free radical management. Our results reveal a fundamental mechanism by which key elements of energy metabolism may modulate the substrates of hippocampal synaptic plasticity.
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insulin like growth Factor i interfaces with brain derived Neurotrophic Factor mediated synaptic plasticity to modulate aspects of exercise induced cognitive function
Neuroscience, 2006Co-Authors: Qinxue Ding, Shoshanna Vaynman, Zhe Ying, Maziar Mohammad Akhavan, Fernando GomezpinillaAbstract:The ability of exercise to benefit neuronal and cognitive plasticity is well recognized. This study reveals that the effects of exercise on brain neuronal and cognitive plasticity are in part modulated by a central source of insulin-like growth Factor-I. Exercise selectively increased insulin-like growth Factor-I expression without affecting insulin-like growth Factor-II expression in the rat hippocampus. To determine the role that insulin-like growth Factor-I holds in mediating exercise-induced neuronal and cognitive enhancement, a specific antibody against the insulin-like growth Factor-I receptor was used to block the action of insulin-like growth Factor-I in the hippocampus during a 5-day voluntary exercise period. A two-trial-per-day Morris water maze was performed for five consecutive days, succeeded by a probe trial 2 days later. Blocking hippocampal insulin-like growth Factor-I receptors did not significantly attenuate the ability of exercise to enhance learning acquisition, but abolished the effect of exercise on augmenting recall. Blocking the insulin-like growth Factor-I receptor significantly reversed the exercise-induced increase in the levels of Brain-Derived Neurotrophic Factor mRNA and protein and pro-Brain-Derived Neurotrophic Factor protein, suggesting that the effects of insulin-like growth Factor-I may be partially accomplished by modulating the precursor to the mature Brain-Derived Neurotrophic Factor. A molecular analysis revealed that exercise significantly elevated proteins downstream to Brain-Derived Neurotrophic Factor activation important for synaptic function, i.e. synapsin I, and signal transduction cascades associated with memory processes, i.e. phosphorylated calcium/calmodulin protein kinase II and phosphorylated mitogen-activated protein kinase II. Blocking the insulin-like growth Factor-I receptor abolished these exercise-induced increases. Our results illustrate a possible mechanism by which insulin-like growth Factor-I interfaces with the Brain-Derived Neurotrophic Factor system to mediate exercise-induced synaptic and cognitive plasticity.
Terence Y. Pang - One of the best experts on this subject based on the ideXlab platform.
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Differential effects of voluntary physical exercise on behavioral and Brain-Derived Neurotrophic Factor expression deficits in huntington’s disease transgenic mice
Neuroscience, 2006Co-Authors: Terence Y. Pang, Nathan C. Stam, Jess Nithianantharajah, Monique L. Howard, Anthony J. HannanAbstract:Huntington's disease is a fatal neurodegenerative disorder caused by a mutation of the huntingtin gene and involves progressive motor abnormalities (including chorea), cognitive deficits (dementia) as well as psychiatric symptoms. We have previously demonstrated that environmental enrichment slows the onset and progression of Huntington's disease in transgenic mice. Here, we investigated the effects of enhanced physical exercise on disease progression and Brain-Derived Neurotrophic Factor expression. Standard-housed Huntington's disease mice developed phenotypic rear-paw clasping by 16 weeks of age, displayed abnormal rearing behavior, deficits in motor co-ordination and of spatial working memory. Huntington's disease mice with access to running wheels exhibited delayed onset of rear-paw clasping, normalized levels of rearing behavior and amelioration of the cognitive deficits. However, in contrast to our previous environmental enrichment studies, there was no rescue of motor coordination deficits in wheel-running Huntington's disease mice. An abnormal accumulation of Brain-Derived Neurotrophic Factor protein in the frontal cortex of Huntington's disease mice was unaffected by running. Striatal and hippocampal Brain-Derived Neurotrophic Factor protein levels were unchanged. Brain-Derived Neurotrophic Factor mRNA levels were reduced in the anterior cortex, striatum and hippocampus of Huntington's disease mice, and only striatal deficits were ameliorated by running. Overall, we show that voluntary physical exercise delays the onset of Huntington's disease and the decline in cognitive ability. In addition, our results reveal that some aspects of hippocampal dependent memory are not entirely reliant on sustained hippocampal Brain-Derived Neurotrophic Factor expression.
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differential effects of voluntary physical exercise on behavioral and brain derived Neurotrophic Factor expression deficits in huntington s disease transgenic mice
Neuroscience, 2006Co-Authors: Terence Y. Pang, Nathan C. Stam, Jess Nithianantharajah, Monique L. Howard, Anthony J. HannanAbstract:Huntington's disease is a fatal neurodegenerative disorder caused by a mutation of the huntingtin gene and involves progressive motor abnormalities (including chorea), cognitive deficits (dementia) as well as psychiatric symptoms. We have previously demonstrated that environmental enrichment slows the onset and progression of Huntington's disease in transgenic mice. Here, we investigated the effects of enhanced physical exercise on disease progression and Brain-Derived Neurotrophic Factor expression. Standard-housed Huntington's disease mice developed phenotypic rear-paw clasping by 16 weeks of age, displayed abnormal rearing behavior, deficits in motor co-ordination and of spatial working memory. Huntington's disease mice with access to running wheels exhibited delayed onset of rear-paw clasping, normalized levels of rearing behavior and amelioration of the cognitive deficits. However, in contrast to our previous environmental enrichment studies, there was no rescue of motor coordination deficits in wheel-running Huntington's disease mice. An abnormal accumulation of Brain-Derived Neurotrophic Factor protein in the frontal cortex of Huntington's disease mice was unaffected by running. Striatal and hippocampal Brain-Derived Neurotrophic Factor protein levels were unchanged. Brain-Derived Neurotrophic Factor mRNA levels were reduced in the anterior cortex, striatum and hippocampus of Huntington's disease mice, and only striatal deficits were ameliorated by running. Overall, we show that voluntary physical exercise delays the onset of Huntington's disease and the decline in cognitive ability. In addition, our results reveal that some aspects of hippocampal dependent memory are not entirely reliant on sustained hippocampal Brain-Derived Neurotrophic Factor expression.
Mark R. Plummer - One of the best experts on this subject based on the ideXlab platform.
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Brain-Derived Neurotrophic Factor modulates hippocampal synaptic transmission by increasing N-methyl-d-aspartic acid receptor activity
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Eric S. Levine, Robert A. Crozier, Ira B. Black, Mark R. PlummerAbstract:Neurotrophins (NTs) have recently been found to regulate synaptic transmission in the hippocampus. Whole-cell and single-channel recordings from cultured hippocampal neurons revealed a mechanism responsible for enhanced synaptic strength. Specifically, Brain-Derived Neurotrophic Factor augmented glutamate-evoked, but not acetylcholine-evoked, currents 3-fold and increased N-methyl-d-aspartic acid (NMDA) receptor open probability. Activation of trkB NT receptors was critical, as glutamate currents were not affected by nerve growth Factor or NT-3, and increased open probability was prevented by the tyrosine kinase inhibitor K-252a. In addition, the NMDA receptor antagonist MK-801 blocked Brain-Derived Neurotrophic Factor enhancement of synaptic transmission, further suggesting that NTs modulate synaptic efficacy via changes in NMDA receptor function.