Biomedical subjects

S Vaynman

Publications and source records attributed to S Vaynman.

6 recordsLinked to original sources

PubMed2006

The select action of hippocampal calcium calmodulin protein kinase II in mediating exercise-enhanced cognitive function.

We found that a single week of exercise enhanced cognitive function on the Morris water maze (MWM), such that exercise animals were significantly better than sedentary controls at learning and recalling the location of the platform. In order to elucidate the role that calcium calmodulin protein kinase II (CAMKII) holds in mediating the exercise-induced enhancement in learning and memory, a specific antagonist of CAMKII, KN-62, was used to block CAMKII in the rat hippocampus during a 1-week voluntary exercise period. Following, a two-trial-per-day MWM was performed for five consecutive days, succeeded by a probe trial 2 days later. Inhibiting CAMKII action during exercise blocked the ability of exercise to enhance memory retention on the MWM; the recall abilities of exercise animals receiving the CAMKII blocker were significantly worse than those of both sedentary and exercise controls. Conversely, CAMKII may not play a significant role in mediating the effects of exercise on learning acquisition as inhibiting CAMKII failed to block the exercise-induced enhancement in learning acquisition. Our results also show that CAMKII activation early during MWM learning may be counterproductive to learning acquisition, as exercising animals given the CAMKII inhibitor performed significantly (P<0.001) better than exercising control animals and sedentary controls only on day 2 of the MWM. Inhibiting CAMKII also blocked the exercise-induced upregulation of molecules critical for learning and memory, brain-derived neurotrophic factor (BDNF) and the transcription activator cAMP response-element-binding protein, which is regulated by and downstream to BDNF action. These findings indicate that hippocampal CAMKII may have a refined role in mediating the effects of exercise on cognition, selectively functioning to regulate memory retention.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2006

Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function.

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.

Animals↗

PubMed2006

Coupling energy metabolism with a mechanism to support brain-derived neurotrophic factor-mediated synaptic plasticity.

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.

Analysis of Variance↗

PubMed2005

A "deficient environment" in prenatal life may compromise systems important for cognitive function by affecting BDNF in the hippocampus.

The intrauterine environment has the capacity to mold the prenatal nervous system. Particularly, recent findings show that an adverse prenatal environment produces structural defects of the hippocampus, a critical area sub-serving learning and memory functions. These structural changes are accompanied by a disruption in the normal expression pattern of brain-derived neurotrophic factor (BDNF) and its cognate tyrosine kinase B (TrkB) receptor. The important role that the BDNF system plays in neural modeling and learning and memory processes suggests that fetal exposure to unfavorable intrauterine conditions may compromise proper cognitive function in adult life. These findings have implications for disorders that involve a dysfunction in the BDNF system and are accompanied by cognitive deficits.

Animals↗

PubMed2004

Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor.

A diet high in total fat (HF) reduces hippocampal levels of brain-derived neurotrophic factor (BDNF), a crucial modulator of synaptic plasticity, and a predictor of learning efficacy. We have evaluated the capacity of voluntary exercise to interact with the effects of diet at the molecular level. Animal groups were exposed to the HF diet for 2 months with and without access to voluntary wheel running. Exercise reversed the decrease in BDNF and its downstream effectors on plasticity such as synapsin I, a molecule with a key role in the modulation of neurotransmitter release by BDNF, and the transcription factor cyclic AMP response element binding protein (CREB), important for learning and memory. Furthermore, we found that exercise influenced the activational state of synapsin as well as of CREB, by increasing the phosphorylation of these molecules. In addition, exercise prevented the deficit in spatial learning induced by the diet, tested in the Morris water maze. Furthermore, levels of reactive oxygen species increased by the effects of the diet were decreased by exercise. Results indicate that exercise interacts with the same molecular systems disrupted by the HF diet, reversing their effects on neural function. Reactive oxygen species, and BDNF in conjunction with its downstream effectors on synaptic and neuronal plasticity, are common molecular targets for the action of the diet and exercise. Results unveil a possible molecular mechanism by which lifestyle factors can interact at a molecular level, and provide information for potential therapeutic applications to decrease the risk imposed by certain lifestyles.

Animals↗

PubMed2003

Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity.

This study was designed to identify molecular mechanisms by which exercise affects synaptic-plasticity in the hippocampus, a brain area whose function, learning and memory, depends on this capability. We have focused on the central role that brain-derived neurotrophic factor (BDNF) may play in mediating the effects of exercise on synaptic-plasticity. In fact, this impact of exercise is exemplified by our finding that BDNF regulates the mRNA levels of two end products important for neural function, i.e. cAMP-response-element binding (CREB) protein and synapsin I. CREB and synapsin I have the ability to modify neuronal function by regulating gene-transcription and affecting synaptic transmission, respectively. Furthermore, we show that BDNF is capable of concurrently increasing the mRNA levels of both itself and its tyrosine kinaseB (TrkB) receptor, suggesting that exercise may employ a feedback loop to augment the effects of BDNF on synaptic-plasticity. The use of a novel microbead injection method in our blocking experiments and Taqman reverse transcription polymerase reaction (RT-PCR) for RNA quantification, have enabled us to evaluate the contribution of different pathways to the exercise-induced increases in the mRNA levels of BDNF, TrkB, CREB, and synapsin I. We found that although BDNF mediates exercise-induced hippocampal plasticity, additional molecules, i.e. the N-methyl-D-aspartate receptor, calcium/calmodulin protein kinase II and the mitogen-activated protein kinase cascade, modulate its effects. Since these molecules have a well-described association to BDNF action, our results illustrate a basic mechanism through which exercise may promote synaptic-plasticity in the adult brain.

Analysis of Variance↗