Abstract The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes-a type of glial cell-have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes. Copyright 2011 Elsevier Inc. All rights reserved.

Literature has shown that exercise is beneficial for cognitive function in older adults and that aerobic fitness is associated with increased hippocampal tissue and blood volumes. The current study used novel network science methods to shed light on the neurophysiological implications of exercise-induced changes in the hippocampus of older adults. Participants represented a volunteer subgroup of older adults that were part of either the exercise training (ET) or healthy aging educational control (HAC) treatment arms from the Seniors Health and Activity Research Program Pilot (SHARP-P) trial. Following the 4-month interventions, MRI measures of resting brain blood flow and connectivity were performed. The ET group's hippocampal cerebral blood flow (CBF) exhibited statistically significant increases compared to the HAC group. Novel whole-brain network connectivity analyses showed greater connectivity in the hippocampi of the ET participants compared to HAC. Furthermore, the hippocampus was consistently shown to be within the same network neighborhood (module) as the anterior cingulate cortex only within the ET group. Thus, within the ET group, the hippocampus and anterior cingulate were highly interconnected and localized to the same network neighborhood. This project shows the power of network science to investigate potential mechanisms for exercise-induced benefits to the brain in older adults. We show a link between neurological network features and CBF, and it is possible that this alteration of functional brain networks may lead to the known improvement in cognitive function among older adults following exercise.

Elimination of early-formed redundant synapses during postnatal development is essential for functional neural circuit formation. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs). A single CF is strengthened whereas the other CFs are eliminated in each PC dependent on postsynaptic activity in PC, but the underlying mechanisms are largely unknown. Here, we report that brain-derived neurotrophic factor (BDNF) from PC facilitates CF synapse elimination. By PC-specific deletion of BDNF combined with knockdown of BDNF receptors in CF, we show that BDNF acts retrogradely on TrkB in CFs, and facilitates elimination of CF synapses from PC somata during the third postnatal week. We also show that BDNF shares signaling pathway with metabotropic glutamate receptor 1, a key molecule that triggers a canonical pathway for CF synapse elimination. These results indicate that unlike other synapses, BDNF mediates punishment signal for synapse elimination in the developing cerebellum. During development, synapses are selectively strengthened or eliminated by activity-dependent competition. Here, the authors show that BDNF-TrkB retrograde signaling is a unishment signal that leads to elimination of climbing fiber-onto-Purkinje cell synapses in the developing cerebellum.

Exercise that engages the cardiovascular system has a myriad of effects on the body; however, we usually do not give much consideration to the benefits it may have for our minds. An increasing body of evidence suggests that exercise can have some remarkable effects on the brain. In this article, we will introduce how exercise can impact the capacity for neurons in the brain to communicate with one another. To properly convey this information, we will first briefly introduce the field of synaptic plasticity and then examine how the introduction of exercise to the experimental setting can actually alter the basic properties of synaptic plasticity in the brain. Next, we will examine some of the candidate physiological processes that might underlay these alterations. Finally, we will close by noting that, taken together, this data points toward our brains being dynamic systems that are in a continual state of flux and that physical exercise may help us to maximize the performance of both our body and our minds.

BACKGROUND: The present study examined whether aerobic fitness training of older humans can increase brain volume in regions associated with age-related decline in both brain structure and cognition. METHODS: Fifty-nine healthy but sedentary community-dwelling volunteers, aged 60-79 years, participated in the 6-month randomized clinical trial. Half of the older adults served in the aerobic training group, the other half of the older adults participated in the toning and stretching control group. Twenty young adults served as controls for the magnetic resonance imaging (MRI), and did not participate in the exercise intervention. High spatial resolution estimates of gray and white matter volume, derived from 3D spoiled gradient recalled acquisition MRI images, were collected before and after the 6-month fitness intervention. Estimates of maximal oxygen uptake (VO2) were also obtained. RESULTS: Significant increases in brain volume, in both gray and white matter regions, were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning (nonaerobic) control group. As predicted, no significant changes in either gray or white matter volume were detected for our younger participants. CONCLUSIONS: These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans. Furthermore, these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults.

Abstract Cardiovascular fitness is thought to offset declines in cognitive performance, but little is known about the cortical mechanisms that underlie these changes in humans. Research using animal models shows that aerobic training increases cortical capillary supplies, the number of synaptic connections, and the development of new neurons. The end result is a brain that is more efficient, plastic, and adaptive, which translates into better performance in aging animals. Here, in two separate experiments, we demonstrate for the first time to our knowledge, in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task. Specifically, highly fit (Study 1) or aerobically trained (Study 2) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning, when compared with low-fit (Study 1) or nonaerobic control (Study 2) participants. Additionally, in both studies there exist groupwise differences in activation of the anterior cingulate cortex, which is thought to monitor for conflict in the attentional system, and signal the need for adaptation in the attentional network. These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain, and may serve to reduce both biological and cognitive senescence in humans.

react-text: 411 To study the association between performance on psychological tests of executive function and performance on lower extremity tasks with different attentional demands in a large sample of nondemented, older adults. Cross-sectional study. Community-based. Nine hundred twenty-six persons aged 65 and older, without dementia, stroke, parkinsonism, visual impairment, or current treatment with... /react-text react-text: 412 /react-text [Show full abstract]

In this brief review we summarize the promising effects of physical activity and fitness on brain and cognition in children and older adults. Research in children finds that higher fit and more active preadolescent children show greater hippocampal and basal ganglia volume, greater white matter integrity, elevated and more efficient patterns of brain activity, and superior cognitive performance and scholastic achievement. Higher fit and more physically active older adults show greater hippocampal, prefrontal cortex, and basal ganglia volume, greater functional brain connectivity, greater white matter integrity, more efficient brain activity, and superior executive and memory function. Despite these promising results, more randomized trials are needed to understand heterogeneity in response to physical activity, mechanisms, and translation to public policy.

Title: Exercise training increases size of hippocampus and improves memory The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.

ABSTRACT Nearly 200 studies have examined the impact that either acute or long-term exercise has upon cognition. Subsets of these studies have been reviewed using the traditional narrative method, and the common conclusion has been that the results are mixed. Therefore, a more comprehensive review is needed that includes all available studies and that provides a more objective and reproducible review process. Thus, a meta-analytic review was conducted that included all relevant studies with sufficient information for the calculation of effect size (W = 134). The overall effect size was 0.25, suggesting that exercise has a small positive effect on cognition. Examination of the moderator variables indicated that characteristics related to the exercise paradigm, the participants, the cognitive tests, and the quality of the study influence effect size. However, the most important finding was that as experimental rigor decreased, effect size increased. Therefore, more studies need to be conducted that emphasize experimental rigor.

Abstract Declining learning and memory function is associated with the attenuation of adult hippocampal neurogenesis. As in humans, chronic stress or depression in animals is accompanied by hippocampal dysfunction, and neurogenesis is correspondingly down regulated, in part, by the activity of the hypothalamic–pituitary–adrenal axis as well as glutamatergic and serotonergic networks. Antidepressants can reverse this effect over time but one of the most clinically effective moderators of stress or depression and robust stimulators of neurogenesis is simple voluntary physical exercise such as running. Curiously, running also elevates circulating stress hormone levels yet neurogenesis is doubled in running animals. In evaluating the signalling that running provides to the central nervous system in mice, we have found that peripheral vascular endothelial growth factor (VEGF) is necessary for the effects of running on adult hippocampal neurogenesis. Peripheral blockade of VEGF abolished running-induced neurogenesis but had no detectable effect on baseline neurogenesis in non-running animals. These data suggest that VEGF is an important element of a ‘somatic regulator’ of adult neurogenesis and that these somatic signalling networks can function independently of the central regulatory networks that are typically considered in the context of hippocampal neurogenesis.

Abstract We measured the distribution of regional cerebral blood flow with positron emission tomography while three subjects moved their hand, shoulder, or leg. The images were coregistered with each individual's anatomic magnetic resonance scans. The data were analyzed for each individual to avoid intersubject averaging and so to preserve individual gyral anatomy. Instead of inspecting all pixels, we prospectively restricted the data analysis to particular areas of interest. These were defined on basis of the anatomic and physiological literature on nonhuman primates. By examining only a subset of areas, we strengthened the power of the statistical analysis and thereby increased the confidence in reporting single subject data. On the lateral convexity, motor related activity was found for all three subjects in the primary motor cortex, lateral premotor cortex, and an opercular area within the premotor cortex. In addition, there was activation of somatosensory cortex (SI), the supplementary somatosensory area (SII) in the Sylvian fissure, and parietal association areas (Brodmann areas 5 and 40). There was also activation in the insula. We suggest that the activation in the dorsal premotor cortex may correspond with dorsal premotor area (PMd) as described in the macaque brain. We propose three hypotheses as to the probable location of vental premotor area (PMv) in the human brain. On the medial surface, motor-related activity was found for all three subjects in the leg areas of the primary motor cortex and somatosensory cortex and also activity for the hand, shoulder, and leg in the supplementary motor area (SMA) on the dorsal medial convexity and in three areas in the cingulate sulcus. We suggest that the three cingulate areas may correspond with rostral cingulate premotor area, dorsal cingulate motor area (CMAd), and ventral cingulate motor area (CMAv) as identified in the macaque brain. Somatotopic mapping was demonstrated in the primary motor and primary somatosensory cortex. In all three subjects, the arm region lay anterior to the leg region in parietal area 5. Also in all three subjects, the arm region lay anterior to the leg region in the supplementary motor cortex.

Abstract The distributed brain systems associated with performance of a verbal fluency task were identified in a nondirected correlational analysis of neurophysiological data obtained with positron tomography. This analysis used a recursive principal-component analysis developed specifically for large data sets. This analysis is interpreted in terms of functional connectivity, defined as the temporal correlation of a neurophysiological index measured in different brain areas. The results suggest that the variance in neurophysiological measurements, introduced experimentally, was accounted for by two independent principal components. The first, and considerably larger, highlighted an intentional brain system seen in previous studies of verbal fluency. The second identified a distributed brain system including the anterior cingulate and Wernicke's area that reflected monotonic time effects. We propose that this system has an attentional bias.

Abstract Plasma levels of corticosterone (B) respond acutely to exercise in all mammals that have been studied, but the literature contains conflicting reports regarding how chronic activity alters this response. We measured acute and chronic effects of voluntary activity on B in a novel animal model, mice selectively bred for high voluntary wheel running. Female mice were housed with or without wheels for 8 wk beginning at 26 days of age. Wheel-access selection mice had significantly higher B at night 8, day 15, and night 29, compared with wheel-access controls. Elevation of B was an acute effect of voluntary exercise. When adjusted for running in the previous 20 min, no difference between wheel-access selection and control animals remained. No training effect on B response was observed. These results are among the strongest evidence that, in some animals, the acute B response is unaffected by chronic voluntary exercise. In mice without wheels, selection mice had significantly higher B than controls at day 15, night 29, and night 50, suggesting that selection resulted in a modulation of the hypothalamic-pituitary-adrenal axis. Growth over the first 4 wk of treatment was significantly and inversely related to average night B levels within each of the four treatment groups.

The presumption that physical activity, i.e. exercise, as an independent and separated factor influences different aspects of cognitive mechanisms is substantially supported by the literature. The investigations of the influence of physical activity on cognitive functioning have offered several mechanisms which could explain this relationship. Physiological mechanisms including increased cerebral blood flow, changes in neurotransmitter release, structural changes in central nervous system and altered arousal levels are based on physical changes that occur in the body as a consequence of the physical activity. There is evidence that physical training selectively increases angiogenesis, synaptogenesis and neurogenesis. The role of central (BDNF) and peripheral (estrogens, corticosteroids, growth hormone, IGF-1) factors in mediation of the effects of physical exercise on brain functions, has been promoted. Also, there is convergent data on molecular and cellular level, as well as on behavioral and systemic level which support the presumption that physical activity is beneficial to cognition. These data emphasizes the importance of promotion of physical activity during the life span for the prevention of contemporary (obesity, diabetes and cardiovascular) diseases and cognitive decline in humans.

Abstract Functional imaging studies have shown that certain brain regions, including posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC), consistently show greater activity during resting states than during cognitive tasks. This finding led to the hypothesis that these regions constitute a network supporting a default mode of brain function. In this study, we investigate three questions pertaining to this hypothesis: Does such a resting-state network exist in the human brain? Is it modulated during simple sensory processing? How is it modulated during cognitive processing? To address these questions, we defined PCC and vACC regions that showed decreased activity during a cognitive (working memory) task, then examined their functional connectivity during rest. PCC was strongly coupled with vACC and several other brain regions implicated in the default mode network. Next, we examined the functional connectivity of PCC and vACC during a visual processing task and show that the resultant connectivity maps are virtually identical to those obtained during rest. Last, we defined three lateral prefrontal regions showing increased activity during the cognitive task and examined their resting-state connectivity. We report significant inverse correlations among all three lateral prefrontal regions and PCC, suggesting a mechanism for attenuation of default mode network activity during cognitive processing. This study constitutes, to our knowledge, the first resting-state connectivity analysis of the default mode and provides the most compelling evidence to date for the existence of a cohesive default mode network. Our findings also provide insight into how this network is modulated by task demands and what functions it might subserve.

Abstract Accepted for publication on March 24, 2017 This study examined the combined effect of physical exercise and cognitive training on memory and neurotrophic factors in young adults. Ninety-five participants completed six weeks of exercise training, combined exercise and cognitive training, or no training (control). Both the exercise and combined training groups improved performance on a high-interference memory task, whereas the control group did not. In contrast, neither training group improved on general recognition performance, suggesting that exercise training selectively increases high-interference memory that may be linked to hippocampal function. Individuals that experienced greater fitness improvements from the exercise training (i.e., high responders to exercise) also had greater increases in the serum neurotrophic factors brain-derived neurotrophic factor (BDNF) and insulin like growth factor-1 (IGF-1). This was accompanied by better high-interference memory performance as a result of the combined exercise and cognitive training compared to exercise alone, suggesting that potential synergistic effects may depend on the availability of neurotrophic factors. These findings are especially important, as memory benefits accrued from a relatively short intervention in high functioning young adults.

Abstract Normal human aging is accompanied by progressive brain tissue loss and cognitive decline; however, several factors are thought to influence brain aging. We applied tensor-based morphometry to high-resolution brain MRI scans to determine whether educational level or physical activity was associated with brain tissue volumes in the elderly, particularly in regions susceptible to age-related atrophy. We mapped the 3D profile of brain volume differences in 226 healthy elderly subjects (130F/96M; 77.9 ± 3.6 SD years) from the Cardiovascular Health Study-Cognition Study. Statistical maps revealed the 3D profile of brain regions whose volumes were associated with educational level and physical activity (based on leisure-time energy expenditure). After controlling for age, sex, and physical activity, higher educational levels were associated with 652–3% greater tissue volumes, on average, in the temporal lobe gray matter. After controlling for age, sex, and education, greater physical activity was associated with 652–2.5% greater average tissue volumes in the white matter of the corona radiata extending into the parietal-occipital junction. Body mass index (BMI) was highly correlated with both education and physical activity, so we examined BMI as a contributing factor by including physical activity, education, and BMI in the same model; only BMI effects remained significant. This is one of the largest MRI studies of factors influencing structural brain aging, and BMI may be a key factor explaining the observed relationship between education, physical activity, and brain structure. Independent contributions to brain structure could not be teased apart as all these factors were highly correlated with one another. Hum Brain Mapp, 2010. 08 2010 Wiley-Liss, Inc.

Abstract The human brain adapts to changing demands by altering its functional and structural properties ("neuroplasticity") which results in learning and acquiring skills. Convergent evidence from both human and animal studies suggests that physical activity facilitates neuroplasticity of certain brain structures and as a result cognitive functions. Animal studies have identified an enhancement of neurogenesis, synaptogenesis, angiogenesis and the release of neurotrophins as neural mechanisms mediating beneficial cognitive effects of physical exercise. This review summarizes behavioral consequences and neural correlates at the system level following physical exercise interventions in humans of different ages. The results suggest that physical exercise may trigger processes facilitating neuroplasticity and, thereby, enhances an individual's capacity to respond to new demands with behavioral adaptations. Indeed, some recent studies have suggested that combining physical and cognitive training might result in a mutual enhancement of both interventions. Moreover, new data suggest that to maintain the neuro-cognitive benefits induced by physical exercise, an increase in the cardiovascular fitness level must be maintained. Copyright 2013 Elsevier Ltd. All rights reserved.

Aerobic exercise has beneficial effects on cognitive functioning in aging humans, especially on executive functions associated with frontal brain regions. In rodents, exercise has been shown to induce structural and neurophysiological changes especially in the hippocampus and to improve spatial learning. The present study investigated the relationship between cardiovascular fitness, spatial learning and associated patterns of brain activation cross-sectionally and longitudinally in a sample of middle-aged men and women (40 55 years) that took part in a six-month exercise intervention and an additional spatial training. Spatial learning capacities before and after the interventions were measured with a virtual maze task. During this task, participants were repeatedly moved through a virtual town and were instructed to infer the spatial layout of the environment. Brain activations during encoding of the virtual town were assessed with functional magnetic resonance imaging ( f MRI). The f MRI data revealed that brain activations during successful spatial learning were modulated by the individual fitness level in a neural network, comprising the hippocampus, retrosplenial cortex, cuneus, precuneus, parahippocampal gyrus, caudate nucleus, insula, putamen, and further frontal, temporal, occipital and cingulate regions. Moreover, physical exercising induced changes in cardiovascular fitness that correlated positively with changes in brain activations in the medial frontal gyrus and the cuneus. However, overall spatial learning performance did not vary with cardiovascular fitness. These data suggest that cardiovascular fitness has an impact on brain regions associated with spatial learning in humans and hence, could be a potent intervention to prevent age-related cognitive decline.

Abstract Brain-derived neurotrophic factor (BDNF), present in minute amounts in the adult central nervous system, is a member of the nerve growth factor (NGF) family, which includes neurotrophin-3 (NT-3). NGF, BDNF and NT-3 all support survival of subpopulations of neural crest-derived sensory neurons; most sympathetic neurons are responsive to NGF, but not to BDNF; NT-3 and BDNF, but not NGF, promote survival of sensory neurons of the nodose ganglion. BDNF, but not NGF, supports the survival of cultured retinal ganglion cells but both NGF and BDNF promote the survival of septal cholinergic neurons in vitro. However, knowledge of their precise physiological role in development and maintenance of the nervous system neurons is still limited. The BDNF gene is expressed in many regions of the adult CNS, including the striatum. A protein partially purified from bovine striatum, a target of nigral dopaminergic neurons, with characteristics apparently similar to those of BDNF, can enhance the survival of dopaminergic neurons in mesencephalic cultures. BDNF seems to be a trophic factor for mesencephalic dopaminergic neurons, increasing their survival, including that of neuronal cells which degenerate in Parkinson's disease. Here we report the effects of BDNF on the survival of dopaminergic neurons of the developing substantia nigra.

Adult hippocampal neurogenesis is an unusual case of brain plasticity, since new neurons (and not just neurites and synapses) are added to the network in an activity-dependent way. At the behavioral level the plasticity-inducing stimuli include both physical and cognitive activity. In reductionistic animal studies these types of activity can be studied separately in paradigms like voluntary wheel running and environmental enrichment. In both of these, adult neurogenesis is increased but the net effect is primarily due to different mechanisms at the cellular level. Locomotion appears to stimulate the precursor cells, from which adult neurogenesis originates, to increased proliferation and maintenance over time, whereas environmental enrichment, as well as learning, predominantly promotes survival of immature neurons, that is the progeny of the proliferating precursor cells. Surprisingly, these effects are additive: boosting the potential for adult neurogenesis by physical activity increases the recruitment of cells following cognitive stimulation in an enriched environment. Why is that? We argue that locomotion actually serves as an intrinsic feedback mechanism, signaling to the brain, including its neural precursor cells, increasing the likelihood of cognitive challenges. In the wild (other than in front of a TV), no separation of physical and cognitive activity occurs. Physical activity might thus be much more than a generally healthy garnish to leading “an active life” but an evolutionarily fundamental aspect of “activity,” which is needed to provide the brain and its systems of plastic adaptation with the appropriate regulatory input and feedback.

This research is aimed to prove if harmful effects of smoking, as the main reason for recently elevated blood vessel disease, could be reduced by aerobic exercise, and identify the positive effects of the aerobic exercise on smokers` blood vessel health(blood pressure, pulse pressure, and blood vessel elasticity. Experiments were performed on 40 male smokers aged between 40 and 55, which was equally divided into two groups of Aerobic Exercise Group (AEG) and Non Exercise Group (NEG). After measuring each group`s blood pressure, pulse pressure, and blood vessel elasticity, AEG practiced aerobic exercise program for 50 minutes for each trial, three times a week, sustaining 12 weeks while NEG continued daily-life patterns without any special treatment. In 12 weeks, blood pressure, pulse pressure, and blood vessel elasticity of both groups were measured as the same way. As a result, the difference of systolic blood pressure between the two groups was not significant, while that of diastolic blood pressure was meaningful. The difference of pulse pressure between the two groups was meaningful, and that of blood vessel elasticity was also meaningful in all measuring points including left hand, right hand, left foot and right foot. As a consequent, it was found that aerobic exercise had positive effects on middle aged male smokers` blood vessel health.

Voluntary wheel running has long been known to induce precursor in adult hippocampal in . However, mechanisms that couple activity with the promitotic effect are not yet fully understood. Using tryptophan hydroxylase () 2 deficient (-deficient) that lack brain , we explored the relationship between signaling and exercise-induced . Surprisingly, -deficient exhibit normal baseline hippocampal but impaired activity-induced proliferation. Our data demonstrate that the proproliferative effect of running requires the release of central in young-adult and aged . Lack of brain further results in alterations at the stage of -positive precursor cells, suggesting physiological adaptations to changes in supply to maintain in the neurogenic niche. We conclude that plays a direct and acute regulatory role in activity-dependent hippocampal . The understanding of exercise-induced might offer preventive but also therapeutic opportunities in and .

Abstract PURPOSE: To assess the efficacy of neck cooling on cognitive performance following exertional hyperthermia. METHODS: Twelve healthy men completed two experimental trials [control (CON) and neck cooling collar (NCC)] in a counter-balanced design. They ran on a treadmill at 70% VO2peak under warm and humid conditions (dry bulb temperature: 30.2 ± 0.3 °C, relative humidity: 71 ± 2 %) for 75 min or until volitional exhaustion. Gastrointestinal, neck and skin temperatures, heart rate and subjective ratings were assessed. Serum brain-derived neurotrophic factor (BDNF) levels were measured before and after each run. Cognitive performance comprising symbol digit matching, search and memory, digit span, choice reaction time and psychomotor vigilance test (PVT) were assessed before and after exercise. RESULTS: Mean gastrointestinal temperature was similar after exercise between trials (CON: 39.5 ± 0.4 °C vs. NCC: 39.6 ± 0.3 °C; p = 0.15). Mean neck temperature was lowered in NCC compared to CON after the run (36.4 ± 1.6 °C vs. NCC: 26.0 ± 0.3 °C; p < 0.001). Exercise-induced hyperthermia improved mean reaction time in the symbol digit matching test (-134 ± 154 ms; p < 0.05) and the PVT (-18 ± 30 ms; p < 0.05). Maximum span was increased in the digit span test (1 ± 2; p < 0.05). Application of NCC reduced the number of search errors made in level 3 of the search and memory test (p < 0.05). Mean serum BDNF levels were increased following exercise-induced hyperthermia in both trials (p < 0.05). CONCLUSION: Exercise-induced hyperthermia improves working memory and alertness. Neck cooling may only enhance performance in tasks of higher complexity.

Executive function declines with age, but engaging in aerobic exercise may attenuate decline. One mechanism by which aerobic exercise may preserve executive function is through the up-regulation of brain-derived neurotropic factor (BDNF), which also declines with age. The present study examined BDNF as a mediator of the effects of a 1-year walking intervention on executive function in 90 older adults (mean age = 66.82). Participants were randomized to a stretching and toning control group or a moderate intensity walking intervention group. BDNF serum levels and performance on a task-switching paradigm were collected at baseline and follow-up. We found that age moderated the effect of intervention group on changes in BDNF levels, with those in the highest age quartile showing the greatest increase in BDNF after 1-year of moderate intensity walking exercise (p= 0.036). The mediation analyses revealed that BDNF mediated the effect of the intervention on task-switch accuracy, but did so as a function of age, such that exercise-induced changes in BDNF mediated the effect of exercise on task-switch performance only for individuals over the age of 71. These results demonstrate that both age and BDNF serum levels are important factors to consider when investigating the mechanisms by which exercise interventions influence cognitive outcomes, particularly in elderly populations.

Abstract BACKGROUND: Persistent inflammation is involved in the pathogenesis of chronic diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). AIMS: The aim of this review was to provide the reader with an update of the mechanisms whereby exercise-induced cytokines may impact cardiometabolic diseases. RESULTS: Evidence exists that interleukin (IL)-10205 is involved in pancreatic 0205-cell damage, whereas TNF-02± is a key molecule in peripheral insulin resistance. In addition, TNF-02± appears to be involved in the pathogenesis of atherosclerosis and heart failure. A marked increase in IL-6 and IL-10 is provoked by exercise and exerts direct anti-inflammatory effects by an inhibition of TNF-02± and by stimulating IL-1ra, thereby limiting IL-10205 signalling. Moreover, muscle-derived IL-6 appears to have direct anti-inflammatory effects and serves as a mechanism to improve glucose tolerance. In addition, indirect anti-inflammatory effects of long-term exercise are mediated via improvements in body composition. CONCLUSION: Physical activity represents a natural, strong anti-inflammatory strategy with minor side effects and should be integrated in the management of patients with cardiometabolic diseases. 0008 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Abstract PURPOSE: To assess intrinsic properties of water diffusion in normal human brain by using quantitative parameters derived from the diffusion tensor, D, which are insensitive to patient orientation. MATERIALS AND METHODS: Maps of the principal diffusivities of D, of Trace(D), and of diffusion anisotropy indices were calculated in eight healthy adults from 31 multisection, interleaved echo-planar diffusion-weighted images acquired in about 25 minutes. RESULTS: No statistically significant differences in Trace(D) (approximately 2,100 x 10(-6) mm2/sec) were found within normal brain parenchyma, except in the cortex, where Trace(D) was higher. Diffusion anisotropy varied widely among different white matter regions, reflecting differences in fiber-tract architecture. In the corpus callosum and pyramidal tracts, the ratio of parallel to perpendicular diffusivities was approximately threefold higher than previously reported, and diffusion appeared cylindrically symmetric. However, in other white matter regions, particularly in the centrum semiovale, diffusion anisotropy was low, and cylindrical symmetry was not observed. Maps of parameters derived from D were also used to segment tissues based on their diffusion properties. CONCLUSION: A quantitative characterization of water diffusion in anisotropic, heterogeneously oriented tissues is clinically feasible. This should improve the neuroradiologic assessment of a variety of gray and white matter disorders.

We examine evidence supporting the associations among physical activity (PA), cognitive vitality, neural functioning, and the moderation of these associations by genetic factors. Prospective epidemiological studies provide evidence for PA to be associated with a modest reduction in relative risk of cognitive decline. An evaluation of the PA-cognition link across the life span provides modest support for the effect of PA on preserving and even enhancing cognitive vitality and the associated neural circuitry in older adults, with the majority of benefits seen for tasks that are supported by the prefrontal cortex and the hippocampus. The literature on children and young adults, however, is in need of well-powered randomized controlled trials. Future directions include a more sophisticated understanding of the dose-response relationship, the integration of genetic and epigenetic approaches, inclusion of multimodal imaging of brain-behavior changes, and finally the design of multimodal interventions that may yield broader improvements in cognitive function.

Abstract This study examined whether regular exercise training, at a level that would be recommended for middle-aged people interested in improving fitness could lead to improved cognitive performance and increased blood flow to the brain in another primate species. Adult female cynomolgus monkeys were trained to run on treadmills for 1 h a day, 5 days a week, for a 5 month period (n=16; 1.9+/-0.4 miles/day). A sedentary control group sat daily on immobile treadmills (n=8). Half of the runners had an additional sedentary period for 3 months at the end of the exercise period (n=8). In all groups, half of the monkeys were middle-aged (10-12 years old) and half were more mature (15-17 years old). Starting the fifth week of exercise training, monkeys underwent cognitive testing using the Wisconsin General Testing Apparatus (WGTA). Regardless of age, the exercising group learned to use the WGTA significantly faster (4.6+/-3.4 days) compared to controls (8.3+/-4.8 days; P=0.05). At the end of 5 months of running monkeys showed increased fitness, and the vascular volume fraction in the motor cortex in mature adult running monkeys was increased significantly compared to controls (P=0.029). However, increased vascular volume did not remain apparent after a 3-month sedentary period. These findings indicate that the level of exercise associated with improved fitness in middle-aged humans is sufficient to increase both the rate of learning and blood flow to the cerebral cortex, at least during the period of regular exercise. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Long-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or 伪CamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.

Abstract We have recently shown that a single bout of acute cardiovascular exercise improves motor skill learning through an optimization of long-term motor memory. Here we expand this previous finding, to explore potential exercise-related biomarkers and their association with measures of motor memory and skill acquisition. Thirty-two healthy young male subjects were randomly allocated into either an exercise or control group. Following either an intense bout of cycling or rest subjects practiced a visuomotor tracking task. Motor skill acquisition was assessed during practice and retention 1 h, 24 h and 7 days after practice. Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), epinephrine, norepinephrine, dopamine and lactate were analyzed at baseline, immediately after exercise or rest and during motor practice. The exercise group showed significantly better skill retention 24h and 7 days after acquisition. The concentration of all blood compounds increased significantly immediately after exercise and remained significantly elevated for 15 min following exercise except for BDNF and VEGF. Higher concentrations of norepinephrine and lactate immediately after exercise were associated with better acquisition. Higher concentrations of BDNF correlated with better retention 1 h and 7 days after practice. Similarly, higher concentrations of norepinephrine were associated with better retention 7 days after practice whereas lactate correlated with better retention 1h as well as 24 h and 7 days after practice. Thus, improvements in motor skill acquisition and retention induced by acute cardiovascular exercise are associated with increased concentrations of biomarkers involved in memory and learning processes. More mechanistic studies are required to elucidate the specific role of each biomarker in the formation of motor memory. Copyright 2014 Elsevier Inc. All rights reserved.

Successful ageing is determined in part by genetic background, but also by experiential factors associated with lifestyle and culture. Dietary, behavioural and pharmacological interventions have been identified as potential means to slow brain ageing and forestall neurodegenerative disease. Many of these interventions recruit adaptive cellular stress responses to strengthen neuronal networks and enhance plasticity. In this Science and Society article, we describe several determinants of healthy and pathological brain ageing, with insights into how these processes are accelerated or prevented. We also describe the mechanisms underlying the neuroprotective actions of exercise and nutritional interventions, with the goal of recruiting these molecular targets for the treatment and prevention of neurodegenerative disease.

The primary objective of this first chapter is to provide a brief overview and synthesis of the subsequent chapters in this book and to elaborate on some favorite subjects, such as the role of microglia in the normal brain and their role in Alzheimer disease. Other pathological conditions where microglia are thought to play important roles, such as autoimmune CNS inflammatory disease, experimental allergic encephalomyelitis and multiple sclerosis, or infectious diseases such as HIV, will not be covered specifically in this book, but there are excellent reviews available on these topics (Gonzalez-Scarano and Baltuch (1999); Benveniste et al. (1997)).

Exercise seems a simple and widely practised behaviour that activates molecular and cellular signalling cascades involved in various central nervous system processes. Despite impressive results obtained in animal studies, fitness interventions have produced less reliable effects in humans, particularly in young adults. In the present study we tested the hypothesis that an individually adapted exercise training consisting of three running sessions of 30 minutes per week for 6 weeks, has the potential to improve visuospatial and verbal memory, concentration performance, and affect in young and healthy adults. Twenty-eight students participated and underwent a graded fitness test to assess individual fitness. The experimental group took part in an aerobic running programme, whereas the control group were asked not to vary their everyday activities. We found a significant increase in visuospatial memory performance and a significant increase in positive affect on a .05 alpha level of significance. However, we observed no effects of running training on concentration performance and verbal memory. We conclude that physical activity can possibly serve as a means to improve positively valenced aspects of affect and benefit visuospatial but not verbal memory in young adults.

Abstract Aerobic activity is a powerful stimulus for improving mental health and for generating structural changes in the brain. We review the literature documenting these structural changes and explore exactly where in the brain these changes occur as well as the underlying substrates of the changes including neural, glial, and vasculature components. Aerobic activity has been shown to produce different types of changes in the brain. The presence of novel experiences or learning is an especially important component in how these changes are manifest. We also discuss the distinct time courses of structural brain changes with both aerobic activity and learning as well as how these effects might differ in diseased and elderly groups.

Significant progress has been made in understanding the neurobiological mechanisms through which exercise protects and restores the brain. In this feature review, we integrate animal and human research, examining physical activity effects across multiple levels of description (neurons up to inter-regional pathways). We evaluate the influence of exercise on hippocampal structure and function, addressing common themes such as spatial memory and pattern separation, brain structure and plasticity, neurotrophic factors, and vasculature. Areas of research focused more within species, such as hippocampal neurogenesis in rodents, also provide crucial insight into the protective role of physical activity. Overall, converging evidence suggests exercise benefits brain function and cognition across the mammalian lifespan, which may translate into reduced risk for Alzheimer's disease (AD) in humans.

react-text: 105 Rural health is an important priority in many jurisdictions as an example of social accountability. The choice to practice in a rural community can be influenced by personal factors, educational factors, and systemic factors. Medical education makes significant contribution to rural health by proactively and positively modifying the educational factors. The experience of the Faculty of... /react-text react-text: 106 /react-text [Show full abstract]

61Exercise induces FNDC5 in the hippocampus61PGC-1α regulates neuronal Fndc5 gene expression in02vitro and in02vivo61FNDC5 positively regulates the expression of the important neurotrophin BDNF61Peripheral delivery of FNDC5 via adenoviral vectors induces Bdnf in the hippocampus

The aim of this large-sample cross-sectional voxel-based morphometry (VBM) study of anatomical brain data was to investigate linear and nonlinear age-related trajectories of grey matter volume in the human brain during the adult lifespan. To date, there are only a few structural brain studies investigating local nonlinear aspects at the voxel level, i.e., without using anatomical ROIs as a priori hypothesis. Therefore, we analyzed 547 T1-weighted MR images of healthy adult brains with an age range of 19 to 86 years, including 161 scans of subjects with ages 60 and older. We found that the gray matter volume in some regions did not linearly decrease over time, but rather exhibited a delayed decline. Nonlinear age trajectories were observed in the medial temporal lobe regions, the basal ganglia, and parts of the cerebellum. Their trajectories indicated a preservation of grey matter volume during the early adult lifespan. Interestingly, we found nonlinear grey matter structural dynamics specifically in parts of the brain that have been extensively discussed in the context of learning and memory. We propose a hypothesis in relation to the functional role of these brain regions that may explain these results. Hum Brain Mapp 33:2377 2389, 2012. 2011 Wiley Periodicals, Inc.