Elsa Heyman

Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects.

Exercise is known to induce a cascade of molecular and cellular processes that support brain plasticity. Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin that is also intimately connected with central and peripheral molecular processes of energy metabolism and homeostasis, and could play a crucial role in these induced mechanisms.This review provides an overview of the current knowledge on the effects of acute exercise and/or training on BDNF in healthy subjects and in persons with a chronic disease or disability. A systematic and critical literature search was conducted. Articles were considered for inclusion in the review if they were human studies, assessed peripheral (serum and/or plasma) BDNF and evaluated an acute exercise or training intervention. Nine RCTs, one randomized trial, five non-randomized controlled trials, five non-randomized non-controlled trials and four retrospective observational studies were analysed. Sixty-nine percent of the studies in healthy subjects and 86%of the studies in persons with a chronic disease or disability, showed a ‘mostly transient’ increase in serum or plasma BDNF concentration following an acute aerobic exercise. The two studies regarding a single acute strength exercise session could not show a significant influence on basal BDNF concentration. In studies regarding the effects of strength or aerobic training on BDNF, a difference should be made between effects on basal BDNF concentration and training-induced effects on the BDNF response following an acute exercise. Only three out of ten studies on aerobic or strength training (i.e. 30%) found a training-induced increase in basal BDNF concentration. Two out of six studies (i.e. 33%) reported a significantly higher BDNF response to acute exercise following an aerobic or strength training programme (i.e. compared with the BDNF response to an acute exercise at baseline). A few studies of low quality (i.e. retrospective observational studies) show that untrained or moderately trained healthy subjects have higher basal BDNF concentrations than highly trained subjects. Yet, strong evidence still has to come from good methodological studies.Available results suggest that acute aerobic, but not strength exercise increases basal peripheral BDNF concentrations, although the effect is transient. From a few studies we learn that circulating BDNF originates both from central and peripheral sources. We can only speculate which central regions and peripheral sources in particular circulating BDNF originates from, where it is transported to and to what purpose it is used and/or stored at its final destination. No study could show a long-lasting BDNF response to acute exercise or training (i.e. permanently increased basal peripheral BDNF concentration) in healthy subjects or persons with a chronic disease or disability. It seems that exercise and/or training temporarily elevate basal BDNF and possibly upregulate cellular processing of BDNF (i.e. synthesis, release, absorption and degradation). From that point of view, exercise and/or training would result in a higher BDNF synthesis following an acute exercise bout (i.e. compared with untrained subjects). Subsequently, more BDNF could be released into the blood circulation which may, in turn, be absorbed more efficiently by central and/or peripheral tissues where it could induce a cascade of neurotrophic and neuroprotective effects.

Intense exercise increases circulating endocannabinoid and BDNF levels in humans—Possible implications for reward and depression

The endocannabinoid system is known to have positive effects on depression partly through its actions on neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF). As BDNF is also considered the major candidate molecule for exercise-induced brain plasticity, we hypothesized that the endocannabinoid system represents a crucial signaling system mediating the beneficial antidepressant effects of exercise. Here we investigated, in 11 healthy trained male cyclists, the effects of an intense exercise (60 min at 55% followed by 30 min at 75% W(max)) on plasma levels of endocannabinoids (anandamide, AEA and 2-arachidonoylglycerol, 2-AG) and their possible link with serum BDNF. AEA levels increased during exercise and the 15 min recovery (P<0.001), whereas 2-AG concentrations remained stable. BDNF levels increased significantly during exercise and then decreased during the 15 min of recovery (P<0.01). Noteworthy, AEA and BDNF concentrations were positively correlated at the end of exercise and after the 15 min recovery (r>0.66, P<0.05), suggesting that AEA increment during exercise might be one of the factors involved in exercise-induced increase in peripheral BDNF levels and that AEA high levels during recovery might delay the return of BDNF to basal levels. AEA production during exercise might be triggered by cortisol since we found positive correlations between these two compounds and because corticosteroids are known to stimulate endocannabinoid biosynthesis. These findings provide evidence in humans that acute exercise represents a physiological stressor able to increase peripheral levels of AEA and that BDNF might be a mechanism by which AEA influences the neuroplastic and antidepressant effects of exercise.

Acute norepinephrine reuptake inhibition decreases performance in normal and high ambient temperature

Combined inhibition of dopamine (DA)/norepinephrine (NE) reuptake improves exercise performance and increases core temperature in the heat. A recent study demonstrated that this effect may primarily be related to increased DA activity. NE reuptake inhibition (NERI), however, has received little attention in humans, certainly in the heat, where central fatigue appears to be a main factor influencing performance. Therefore the present study examines the effect of NERI (reboxetine) on exercise capacity, thermoregulation, and hormonal response in normal and high temperature. Nine healthy well-trained male cyclists participated in this study. Subjects ingested either placebo (Pla; 2 x 8 mg) or reboxetine (Rebox; 2 x 8 mg). Subjects exercised in temperate (18 degrees C) or warm (30 degrees C) conditions and cycled for 60 min at 55% W(max) immediately followed by a time trial (TT; Pla18/Rebox18; Pla30/Rebox30) to measure exercise performance. Acute NERI decreased power output and consequently exercise performance in temperate (P = 0.018) and warm (P = 0.007) conditions. Resting heart rate was significantly elevated by NERI (18 degrees C: P = 0.02; 30 degrees C: P = 0.018). In Rebox18, heart rate was significantly higher than in the Pla18, while in the heat no effect of the drug treatment was reported during exercise. In Rebox30, all hormone concentrations increased during exercise, except for growth hormone (GH), which was significantly lower during exercise. In Rebox18, prolactin (PRL) concentrations were significantly elevated; GH was significantly higher at rest, but significantly lower during exercise. In conclusion, manipulation of the NE system decreases performance and modifies hormone concentrations, thereby indicating a central NE effect of the drug. These findings confirm results from previous studies that predominantly increased DA activity is important in improving performance.

Effects of different types of acute and chronic (training) exercise on glycaemic control in type 1 diabetes mellitus: a meta-analysis

OBJECTIVE Exercise has been accepted and generally recommended for the management of type 1 diabetes mellitus (T1D) and for improving the overall quality of life in affected individuals. This meta-analysis was conducted to determine the overall effects of exercise (acute bouts of exercise and chronic exercise [or training]) on acute and chronic glycaemic control in patients with T1D, the effects of different types of exercise on glycaemic control and which conditions are required to obtain these positive effects. METHODS PubMed, ISI Web of Knowledge and SPORTDiscus™ were consulted to identify studies on T1D and exercise. Cohens d statistics were used for calculating mean effect sizes (ES) as follows: small d = 0.3, medium d = 0.5 and large d = 0.8. Ninety-five percent confidence intervals (95% CIs) were used to establish the significance of our findings. RESULTS From a total of 937 studies, 33 that met the inclusion criteria were selected. Nine studies were used to calculate the ES of a single bout of aerobic exercise; 13 studies to calculate the ES of aerobic training; 2 studies to calculate the ES of strength training; 4 studies to calculate the ES of combined (aerobic and strength) training and 6 studies to calculate the ES of high-intensity exercise (HIE) and training. ES for exercise on acute glycaemic control were large, while they were small for chronic glycaemic control. Aerobic exercise, resistance exercise, mixed exercise (aerobic combined with resistance training) and HIE acutely decreased blood glucose levels. To prevent late-onset hypoglycaemic episodes, the use of single bouts of sprints into an aerobic exercise can be recommended. This meta-analysis also showed that a regular exercise training programme has a significant effect on acute and chronic glycaemic control, although not all exercise forms showed significant results. Specifically, aerobic training is a favourable tool for decreasing chronic glycaemic control, while resistance training, mixed and HIE did not significantly improve chronic glycaemic control. Although, this meta-analysis showed there was a tendency for improvement in glycaemic control due to resistance training or resistance training combined with endurance training, there were not enough studies and/or subjects to confirm this statistically. CONCLUSIONS Based on this meta-analysis, we can conclude that the addition of brief bouts of high-intensity, sprint-type exercise to aerobic exercise can minimize the risk of sustaining a hypoglycaemic episode. We can also conclude that only regular aerobic training will improve the glycated haemoglobin level of a patient with T1D.

Effects of Different Types of Acute and Chronic (Training) Exercise on Glycaemic Control in Type 1 Diabetes Mellitus

ObjectiveExercise has been accepted and generally recommended for the management of type 1 diabetes mellitus (T1D) and for improving the overall quality of life in affected individuals. This meta-analysis was conducted to determine the overall effects of exercise (acute bouts of exercise and chronic exercise [or training]) on acute and chronic glycaemic control in patients with T1D, the effects of different types of exercise on glycaemic control and which conditions are required to obtain these positive effects.MethodsPubMed, ISI Web of Knowledge and SPORTDiscus™ were consulted to identify studies on T1D and exercise. Cohen’s d statistics were used for calculating mean effect sizes (ES) as follows: small d = 0.3, medium d = 0.5 and large d = 0.8. Ninety-five percent confidence intervals (95% CIs) were used to establish the significance of our findings.ResultsFrom a total of 937 studies, 33 that met the inclusion criteria were selected. Nine studies were used to calculate the ES of a single bout of aerobic exercise; 13 studies to calculate the ES of aerobic training; 2 studies to calculate the ES of strength training; 4 studies to calculate the ES of combined (aerobic and strength) training and 6 studies to calculate the ES of high-intensity exercise (HIE) and training. ES for exercise on acute glycaemic control were large, while they were small for chronic glycaemic control. Aerobic exercise, resistance exercise, mixed exercise (aerobic combined with resistance training) and HIE acutely decreased blood glucose levels. To prevent late-onset hypoglycaemic episodes, the use of single bouts of sprints into an aerobic exercise can be recommended. This meta-analysis also showed that a regular exercise training programme has a significant effect on acute and chronic glycaemic control, although not all exercise forms showed significant results. Specifically, aerobic training is a favourable tool for decreasing chronic glycaemic control, while resistance training, mixed and HIE did not significantly improve chronic glycaemic control. Although, this meta-analysis showed there was a tendency for improvement in glycaemic control due to resistance training or resistance training combined with endurance training, there were not enough studies and/or subjects to confirm this statistically.ConclusionsBased on this meta-analysis, we can conclude that the addition of brief bouts of high-intensity, sprint-type exercise to aerobic exercise can minimize the risk of sustaining a hypoglycaemic episode. We can also conclude that only regular aerobic training will improve the glycated haemoglobin level of a patient with T1D.

No influence of noradrenaline manipulation on acute exercise-induced increase of brain-derived neurotrophic factor.

PURPOSE To examine the influence of a selective noradrenaline reuptake inhibitor (SNRI) on the exercise-induced increase in circulating brain-derived neurotrophic factor (BDNF). METHODS In a double-blind, placebo-controlled, crossover design, 11 young, healthy male subjects were treated with either placebo or reboxetine. On each occasion, they performed a 60-min cycling exercise at 55% of their maximal power output (Wmax) followed by a time trial (TT) at 75% of Wmax. HR and ratings of perceived exertion were measured. Blood samples were taken at four time points. RESULTS An increase in serum BDNF was found after exercise without any influence of drug administration on BDNF levels. Serum BDNF returned to resting levels after 15 min of recovery. Time trial (TT) performance was significantly worse after reboxetine intake. Serum cortisol increased in both trials during and after exercise and was significantly higher in the reboxetine trial. Also, HR was increased with reboxetine intake, probably because of the sympathomimetic effect of SNRI. Midterm memory was significantly impaired after the exercise protocol without difference between reboxetine and placebo trial. CONCLUSIONS The administration of an SNRI has no effect on the exercise-induced increase in BDNF. However, effects were seen on serum cortisol, HR, and memory. Future research should focus on the effect of regular exercise training in combination with several reuptake inhibitors in both healthy and depressed subjects on BDNF and memory.

Type 1 diabetes-associated cognitive decline: A meta-analysis and update of the current literature

Type 1 diabetes (T1D) can have a significant impact on brain structure and function, which is referred to as T1D‐associated cognitive decline (T1DACD). Diabetes duration, early onset disease, and diabetes‐associated complications are all proposed as factors contributing to T1DACD. However, there have been no comparisons in T1DACD between children and adults with T1D. To obtain a better insight into the occurrence and effects of T1DACD in T1D, the aim of the present meta‐analysis was to investigate differences between children and adults and to analyse factors contributing T1DACD.

Influence of citalopram and environmental temperature on exercise-induced changes in BDNF

PURPOSE Serum brain-derived neurotrophic factor (BDNF) is known to increase with exercise. This increase is believed to originate from the brain and it is suggested that monoamines are involved in BDNF regulation. Heat exposure could influence the supposed BDNF output from the brain. Therefore, we hypothesized that administration of a selective serotonin reuptake inhibitor could influence the exercise-induced increase in BDNF, and that peripheral BDNF will be higher when exercise is performed in the heat. METHODS Eleven well-trained males performed 4 experimental trials on a cycle ergometer with citalopram or placebo treatment (20 mg in 12 h) in an environmental temperature of 18°C or 30°C. Blood samples (BDNF and cortisol) were taken at 4 time points: at rest, after 60 min at 55% W(max), after a time trial of 30 min at 75% W(max) and following 15 min of recovery. Heart rate and core temperature were measured. RESULTS Performance on the time trial was 20% worse in 30°C compared to 18°C (p<0.01), without influence of citalopram. Serum BDNF was found to be lower under citalopram treatment, while basal cortisol levels were increased (p<0.05). Exercise triggered an increase in both BDNF and cortisol (p<0.001). BDNF followed the same pattern as core temperature during exercise, with higher levels of both variables in 30°C. Cortisol was also increased in 30°C compared to temperate conditions (p<0.01). CONCLUSION Exercise caused a rise in serum BDNF and cortisol. This increase was enhanced with exercise in the heat. Since permeability of the blood-brain barrier increases with exercise in the heat, the hypothesis was raised that this causes a higher cerebral output of BDNF. Serotonergic stimulation did not increase peripheral BDNF, which was even lower with citalopram administration. Future research should focus on mechanisms behind BDNF increase with exercise.

Acute running stimulates hippocampal dopaminergic neurotransmission in rats, but has no influence on brain-derived neurotrophic factor

Hippocampal brain-derived neurotrophic factor (BDNF) protein is increased with exercise in rats. Monoamines seem to play a role in the regulation of BDNF, and monoamine neurotransmission is known to increase with exercise. The purpose of this study was to examine the influence of acute exercise on monoaminergic neurotransmission and BDNF protein concentrations. Hippocampal microdialysis was performed in rats that were subjected to 60 min of treadmill running at 20 m/min or rest. Two hours postexercise, the rats were killed, and the hippocampus was dissected. In experiments without microdialysis, hippocampus and serum samples were collected immediately after exercise. Exercise induced a twofold increase in hippocampal dopamine release. Noradrenaline and serotonin release were not affected. Hippocampal BDNF levels were not influenced, whether they were measured immediately or 2 h after the exercise protocol. Serum BDNF levels did not change either, but serum BDNF was negatively correlated to peripheral corticosterone concentrations, indicating a possible inhibitory reaction to the stress of running. Sixty minutes of exercise enhances dopamine release in the hippocampus of the rat in vivo. However, this increase is not associated with changes in BDNF protein levels immediately nor 2 h after the acute exercise bout. An increased corticosterone level might be the contributing factor for the absence of changes in BDNF.

Type 1 diabetes-associated cognitive decline: A meta-analysis and update of the current literature 1型糖尿病相关的认知能力下降：一项对最新文献的meta分析

Type 1 diabetes (T1D) can have a significant impact on brain structure and function, which is referred to as T1D‐associated cognitive decline (T1DACD). Diabetes duration, early onset disease, and diabetes‐associated complications are all proposed as factors contributing to T1DACD. However, there have been no comparisons in T1DACD between children and adults with T1D. To obtain a better insight into the occurrence and effects of T1DACD in T1D, the aim of the present meta‐analysis was to investigate differences between children and adults and to analyse factors contributing T1DACD.