Brain-derived Neurotrophic Factor Response Research Articles

Serum levels of insulin-like growth factor-1 and brain-derived neurotrophic factor as potential recovery biomarkers in stroke

ABSTRACTObjectives: Our objectives were: 1) to determine whether maximal aerobic exercise increased serum neurotrophins in chronic stroke and 2) to determine the factors that predict resting and exercise-dependent levels.Methods: We investigated the potential predictors of resting and exercise-dependent serum insulin-like growth factor-1 and brain-derived neurotrophic factor among 35 chronic stroke patients. Predictors from three domains (demographic, disease burden, and cardiometabolic) were entered into 4 separate stepwise linear regression models with outcome variables: resting insulin-like growth factor, resting brain-derived neurotrophic factor, exercise-dependent change in insulin-like growth factor, and exercise-dependent change brain-derived neurotrophic factor.Results: Insulin-like growth factor decreased after exercise (p = 0.001) while brain-derived neurotrophic factor did not change (p = 0.38). Greater lower extremity impairment predicted higher resting brain-derived neurotrophic factor (p = 0.004, r2 = 0.23). Higher fluid intelligence predicted greater brain-derived neurotrophic factor response to exercise (p = 0.01, r2 = 0.18). There were no significant predictors of resting or percent change insulin-like growth factor-1.Discussion: Biomarkers have the potential to characterize an individual’s potential for recovery from stroke. Neurotrophins such as insulin-like growth factor-1 and brain-derived neurotrophic factor are thought to be important in neurorehabilitation; however, the factors that modulate these biomarkers are not well understood. Resting brain-derived neurotrophic factor and percent change in brain-derived neurotrophic factor were related to physical and cognitive recovery in chronic stroke, albeit weakly. Insulin-like growth factor-1 was not an informative biomarker among chronic stroke patients. The novel finding that fluid intelligence positively correlated with exercise-induced change in brain-derived neurotrophic factor warrants further research.

Salivary BDNF and Cortisol Responses During High-Intensity Exercise and Official Basketball Matches in Sedentary Individuals and Elite Players.

Salivary cortisol increases in response to stressors, including physical exertion and psychological stress associated with sports competition. In addition, stress may induce change in brain-derived neurotrophic factor (BDNF). However, there are still no data available to compare the salivary BDNF level in sedentary male individuals and elite team-sport male athletes, regularly involved in activities that require elevated attention and concentration. This information could contribute to the advance of understanding of the effect of regular exercise on the salivary level of BDNF, the pre-to-post change in salivary BDNF during exercise, and the association between salivary cortisol and salivary BDNF responses to physical exercise. Therefore, this study aimed to compare the concentration of salivary cortisol and BDNF, before and after exercise, in sedentary individuals and elite male basketball players. The sedentary group (23.0 ± 4.2 yrs) performed a high-intensity exercise protocol and the basketball players (18.6 ± 0.5 yrs) participated in three official basketball matches. Saliva samples were tested for cortisol and BDNF using ELISA. A significant increase in salivary cortisol from pre- to post-match was observed only for the basketball players (p < 0.05). Basketball players also presented a higher salivary BDNF concentration for both resting (pre) and post-physical exercise (p < 0.05); however, no change in pre- to post-exercise salivary BDNF was observed for either group (p > 0.05). Elevated BDNF in athletes may be associated to their repeated exposure to stressful competition situations. The current findings also suggest that different mechanisms might be involved in salivary cortisol and BDNF responses during physical exercise.

Exercise intensity affects acute neurotrophic and neurophysiological responses poststroke

Aerobic exercise may acutely prime the brain to be more responsive to rehabilitation, thus facilitating neurologic recovery from conditions like stroke. This aerobic priming effect could occur through multiple mechanisms, including upregulation of circulating brain-derived neurotrophic factor (BDNF), increased corticospinal excitability, and decreased intracortical inhibition. However, optimal exercise parameters for targeting these mechanisms are poorly understood. This study tested the effects of exercise intensity on acute BDNF and neurophysiological responses. Sixteen ambulatory persons >6 mo poststroke performed three different 20-min exercise protocols in random order, approximately 1 wk apart, including the following: 1) treadmill high-intensity interval training (HIT-treadmill); 2) seated-stepper HIT (HIT-stepper); and 3) treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum BDNF and transcranial magnetic stimulation measures of paretic lower limb excitability and inhibition were assessed at multiple time points during each session. Compared with MCT-treadmill, HIT-treadmill elicited significantly greater acute increases in circulating BDNF and corticospinal excitability. HIT-stepper initially showed BDNF responses similar to HIT-treadmill but was no longer significantly different from MCT-treadmill after decreasing the intensity in reaction to two hypotensive events. Additional regression analyses showed that an intensity sufficient to accumulate blood lactate appeared to be important for eliciting BDNF responses, that the interval training approach may have facilitated the corticospinal excitability increases, and that the circulating BDNF response was (negatively) related to intracortical inhibition. These findings further elucidate neurologic mechanisms of aerobic exercise and inform selection of optimal exercise-dosing parameters for enhancing acute neurologic effects. NEW & NOTEWORTHY Acute exercise-related increases in circulating BDNF and corticospinal excitability are thought to prime the brain for learning. Our data suggest that these responses can be obtained among persons with stroke using short-interval treadmill high-intensity interval training, that a vigorous aerobic intensity sufficient to generate lactate accumulation is needed to increase BDNF, that interval training facilitates increases in paretic quadriceps corticospinal excitability, and that greater BDNF response is associated with lesser intracortical inhibition response.

Maternal and post-natal obesity alters long-term memory and hippocampal molecular signaling of male rat

The aim of this study was to investigate whether maternal cafeteria ingestion interferes with long-term memory-related behaviors and hippocampal brain-derived neurotrophic factor (BDNF) signaling in the offspring, and if there is a cumulative effect with the exposure to cafeteria diet during the life-course of the pups. Female rats were fed a control (CON, n = 20) or cafeteria diet (CAF, n = 24) from their weaning to weaning of their offspring. After that, their male offspring were divided into 4 groups (CON-CON, n = 36; CON-CAF, n = 38, CAF-CON, n = 46 and CAF-CAF, n = 39) so that all litters ingested CON or CAF, irrespective of maternal diet. At 30 days of age, all groups exposed to cafeteria diet at some stage in life showed a decline in performance on one or both object recognition and inhibitory avoidance tasks. At 120 days, CON-CAF and CAF-CAF groups continued to show memory impairment. There were no significant differences between groups in the hippocampal concentrations of BDNF and cAMP Response Element Binding protein (CREB) in puberty or adulthood, but the concentration of hippocampal Ras–Raf–MEK–mitogen-activated protein kinase (MAPK) was higher in CAF-CAF pubescent offspring when compared to the CON-CON group. These data suggest that maternal diet affects the behavior and the molecular signaling related to long-term memory of the offspring, and that its effects are influenced by postnatal diet.

Brain-derived neurotrophic factor: Biopsychosocial correlates and exercise response in mild traumatic brain injury

Recovery from mild traumatic brain injury (mTBI) is a dynamic, complex process, and pre-clinical research highlights brain-derived neurotrophic factor (BDNF) as an important mediator in functional and pathophysiologic outcomes. Although BDNF appears to also be a significant factor in recovery in humans, its role is less understood. Our purpose was (1) to examine the association of serum and platelet-poor plasma concentrations of BDNF to relevant biopsychosocial outcomes of mTBI recovery (i.e., neurocognitive performance [attention, processing speed, memory, executive functioning], sleep, balance, mood, and self-reported symptoms) and (2) to assess BDNF response to a single-session of aerobic exercise (40 minutes of stationary cycling at 65%–75% maximum heart rate). There were 36 participants (ages 18–40; 19 male, 17 female) in 2 groups: (1) mTBI participants (n = 26) who were 14–25 days post-injury were randomized to either aerobic or non-aerobic exercise (low intensity stretching) and (2) demographically-matched, non-injured participants (n = 10) who participated in a single session of aerobic exercise. Results indicate that serum BDNF concentration has significant ( p = 0.05), inverse relationships with both sleep dysfunction and state levels of anxiety. No significant association between exercise type and serum BDNF was found, but there was a small to medium effect size (= 0.08) for increased plasma BDNF after aerobic exercise in mTBI vs non-injured participants. Overall, peripheral BDNF concentrations are poorly correlated, which suggests they reflect different tissue sources. Serum BDNF was more sensitive to select biopsychosocial outcomes, particularly sleep quality and anxiety, regardless of injury status. Additionally, aerobic exercise may play a role in enhancing platelet-poor plasma BDNF response in the post-acute period after mTBI.

Interleukin-10 and brain-derived neurotrophic factor responses to the Mat Pilates training in women with multiple sclerosis

AIMS: To determine the effect of Mat Pilates on serum levels of interleukin-10 and brain-derived neurotrophic factor in women with multiple sclerosis.METHODS: Thirty women with multiple sclerosis with mild to moderate disability were recruited and randomly divided into equal Pilates training and Control groups. Patients in the training group accomplished a Pilates program three times a week for eight weeks. The Control group maintained their routine lifestyle. The serum level of interleukin-10 and brain-derived neurotrophic factor were measured before and after the protocol. The differences between groups were assessed by using analysis of covariance test to compare post-tests by considering covariate pre-tests (assuming a p-value &lt;0.05 as significant).RESULTS: There were no significant changes in interleukin-10 (13.09±5.36 ng/ml in the Pilates training group compared to 13.21±4.76 ng/ml in the Control group, p= 0.81), whereas an increase in brain-derived neurotrophic factor was observed after eight-week Pilates training (11550.14±2619.60 ng/ml in the Pilates training group compared to 9664.35±3161.66 ng/ml in the Control group, p= 0.03).CONCLUSIONS: The results suggest that the intensity and duration of this protocol was not related to significant changes in interleukin-10, but was followed by an increase in brain-derived neurotrophic factor in these patients. Based on this finding, physical activity according to the individual’s ability is recommended for patients with multiple sclerosis, in parallel with drug therapy.

The Impact of High-Intensity Interval Training on Brain Derived Neurotrophic Factor in Brain: A Mini-Review.

The brain-derived neurotrophic factor (BDNF) is a protein mainly synthetized in the neurons. Early evidence showed that BDNF participates in cognitive processes as measured at the hippocampus. This neurotrophin is as a reliable marker of brain function; moreover, recent studies have demonstrated that BDNF participates in physiological processes such as glucose homeostasis and lipid metabolism. The BDNF has been also studied using the exercise paradigm to determine its response to different exercise modalities; therefore, BDNF is considered a new member of the exercise-related molecules. The high-intensity interval training (HIIT) is an exercise protocol characterized by low work volume performed at a high intensity [i.e., ≥80% of maximal heart rate (HRmax)]. Recent evidence supports the contention that HIIT elicits higher fat oxidation in skeletal muscle than other forms of exercise. Similarly, HIIT is a good stimulus to increase maximal oxygen uptake (VO2max). Few studies have investigated the impact of HIIT on the BDNF response. The present work summarizes the effects of acute and long-term HIIT on BDNF.

Fingolimod (FTY720) is not protective in the subacute MPTP mouse model of Parkinson's disease and does not lead to a sustainable increase of brain-derived neurotrophic factor.

Parkinson's disease (PD) is characterized by the loss of midbrain dopaminergic neurons and aggregates of α-synuclein termed Lewy bodies. Fingolimod (FTY720) is an agonist of sphingosine-1 phosphate receptors and an approved oral treatment for multiple sclerosis. Fingolimod elevates brain-derived neurotrophic factor (BDNF), an important neurotrophic factor for dopaminergic neurons. BDNF and fingolimod are beneficial in several animal models of PD. In order to validate the therapeutic potential of fingolimod for the treatment of PD, we tested its effect in the subacute MPTP mouse model of PD. MPTP or vehicle was applied i.p. in doses of 30mg/kg MPTP on five consecutive days. In order to recapitulate the combination of dopamine loss and α-synuclein aggregates found in PD, MPTP was first administered in Thy1-A30P-α-synuclein transgenic mice. Fingolimod was administered i.p. at a dose of 0.1mg/kg every second day. Nigrostriatal degeneration was assayed by stereologically counting the number of dopaminergic neurons in the substantia nigra pars compacta, by analysing the concentration of catecholamines and the density of dopaminergic fibres in the striatum. MPTP administration produced a robust nigrostriatal degeneration, comparable to previous studies. Unexpectedly, we found no difference between mice with and without fingolimod treatment, neither at baseline, nor at 14 or 90days after MPTP. Also, we found no effect of fingolimod in the subacute MPTP mouse model when we used wildtype mice instead of α-synuclein transgenic mice, and no effect with an increased dose of 1mg/kg fingolimod administered every day. In order to explain these findings, we analysed BDNF regulation by fingolimod. We did find an increase of BDNF protein after a single injection of fingolimod 0.1 or 1.0mg/kg, but not after multiple injections, indicating that the BDNF response to fingolimod is unsustainable over time. Taken together we did not observe a neuroprotective effect of fingolimod in the subacute MPTP mouse model of PD. We discuss possible explanations for this discrepancy with previous findings and conclude fingolimod might be beneficial for the nonmotor symptoms of PD. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* and *Open Data* because it provided all relevant information to reproduce the study in the manuscript and because it made the data publicly available. The data can be accessed at https://osf.io/6xgfn/. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

The effect of energy-matched exercise intensity on brain-derived neurotrophic factor and motor learning.

Pairing a bout of high-intensity exercise with motor task practice can enhance motor learning beyond task practice alone, which is thought, in part, to be facilitated by an exercise-related increase in brain-derived neurotrophic factor (BDNF). The purpose of the current study was to examine the effect of different exercise intensities on BDNF levels and motor learning while controlling for exercise-related energy expenditure. Forty-eight young, healthy participants were assigned to one of three groups: high-intensity exercise [High], low-intensity exercise [Low], or quiet rest [Rest]. The duration of the exercise bouts were individually adjusted so that each participant expended 200 kcals regardless of exercise intensity. BDNF was measured before and after exercise or rest. After exercise or rest, all participants practiced a 3-dimensional motor learning task, which involved reach movements made to sequentially presented targets. Retention was tested after 24-h. BDNF genotype was determined for each participant to explore its effects on BDNF and motor learning. All participants equally improved performance, indicated by a reduction in time to complete the task. However, the kinematic profile used to control the reach movement differed by group. The Rest group travelled the shortest distance between the targets, the High group had higher reach speed (peak velocity), and the Low group had earlier peak velocities. The rise in BDNF post-exercise was not significant, regardless of exercise intensity, and the change in BDNF was not associated with motor learning. The BDNF response to exercise did not differ by genotype. However, performance differed between those with the polymorphism (Met carriers) and those without (Val/Val). Compared to the Val/Val genotype, Met carriers had faster response times throughout task practice, which was supported by higher reach speeds and earlier peak velocities. Results indicated that both low and high-intensity exercise can alter the kinematic approach used to complete a reach task, and these changes appear unrelated to a change in BDNF. In addition, the BDNF genotype did not influence BDNF concentration, but it did have an effect on motor performance of a sequential target reach task.

Acute high-intensity interval exercise induces greater levels of serum brain-derived neurotrophic factor in obese individuals.

High-intensity interval exercise (HIIE) has been shown to be a time-efficient exercise strategy that provides similar or superior physiological benefits as traditional continuous moderate-intensity exercise (CME). Our previous study demonstrated an equivalent elevation on the BDNF response in both obese and normal-weight individuals following 30 min of acute CME. To discover a time-efficient exercise strategy to improve brain health in an obese population, the present study found that obese individuals elicit a greater level of BDNF following acute HIIE versus CME than normal-weight individuals. These findings indicate that acute HIIE may be an effective strategy to upregulate BDNF expression in obese individuals.

Brain-derived neurotrophic factor, insulin like growth factor-1 and inflammatory cytokine responses to continuous and intermittent exercise in patients with type 1 diabetes

AimsType 1 diabetes mellitus (T1DM) is an important risk factor for cognitive decline and motor dysfunction due to progressive muscular atrophy. Chronic hyperglycemia may be responsible for impaired vascular function, loss of muscle mass, and morphological abnormalities in the myocytes. For the proper functioning of the neuromuscular system, two crucial growth factors are necessary: brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), whose reduced expressions have been implicated in progressive neuropathy and muscle atrophy in patients with T1DM.The aim of the study was to compare the effects of two different exercise regimes (continuous and intermittent) on BDNF, IGF-1, blood glucose and inflammatory cytokine responses in young adults with and without Type 1 diabetes. MethodsFourteen patients (aged: 26.9 years) with T1DM and age-matched adults without diabetes participated in a 40 min continuous exercise (ExC, 50% of lactate threshold) and a high intensity intermittent exercise (ExInt, 120% of lactate threshold). During the study the patients performed self-monitoring of blood glucose levels (SMBG) under glycemic control. The effects of ExC and ExInt on BDNF, IGF-1, insulin like growth factor binding protein (IGFBP-3), insulin (INS), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β) and tumor necrosis factor alpha (TNF-α) were analyzed. ResultsBDNF and IGF-1 baseline serum levels were significantly lower in the T1DM patients compared to the healthy controls, but we found that ExInt and ExC significantly increase the secretion of BDNF and IGF-1 levels. Significant increases in BDNF and TGF-β levels, higher blood glucose decline, and a lower incidence of hypoglycaemia in ExInt compared to ExC were observed. Lower IGFBP-3 concentrations were revealed in T1DM patients in response to ExInt compared to ExC, suggesting a positive effect on IGF-1/IGFBP-3 ratio and the bioavailability of IGF-1. ConclusionsAccording to our results physical exercise has beneficial effects on serum BDNF and IGF-1 levels. A high-intensity intermittent exercise may be more effective at reducing the risk of exercise-induced glycaemic disorders in the T1DM patients as compared to continuous exercise.

Post-stroke BDNF Concentration Changes Following Physical Exercise: A Systematic Review.

Background: Research over the last two decades has highlighted the critical role of Brain-derived neurotrophic factor (BDNF) in brain neuroplasticity. Studies suggest that physical exercise may have a positive impact on the release of BDNF and therefore, brain plasticity. These results in animal and human studies have potential implications for the recovery from damage to the brain and for interventions that aim to facilitate neuroplasticity and, therefore, the rehabilitation process.Purpose: The aim of this study was to carry out a systematic review of the literature investigating how aerobic exercises and functional task training influence BDNF concentrations post-stroke in humans and animal models.Data Sources: Searches were conducted in PubMed (via National Library of Medicine), SCOPUS (Elsevier), CINAHL with Full Text (EBSCO), MEDLINE 1946—present with daily updates (Ovid) and Cochrane.Study Selection: All of the database searches were limited to the period from January, 2004 to May, 2017.Data Extraction: Two reviewers extracted study details and data. The methodological quality of the studies that used animal models was assessed using the ARRIVE Guidelines, and the study that evaluated human BDNF was assessed using the PEDro Scale.Data Synthesis: Twenty-one articles were included in this review. BDNF measurements were performed systemically (serum/plasma) or locally (central nervous system). Only one study evaluated human BDNF concentrations following physical exercise, while 20 studies were experimental studies using a stroke model in animals. A wide variation was observed in the training protocol between studies, although treadmill walking was the most common type of intervention among the studies. Studies were of variable quality: the studies that used animal models scored from 8/20 to 15/20 according to the ARRIVE Guidelines. The only study that evaluated human subjects scored 5/10 according to the PEDro scale and, which indicates a quality classified as “fair”.Conclusions: The results of the current systematic review suggest that aerobic exercise promotes changes in central BDNF concentrations post-stroke. On the other hand, BDNF responses following functional exercises, such as reaching training and Constraint Induced Movement Therapy (CIMT), seem to be still controversial. Given the lack of studies evaluating post-stroke BDNF concentration following physical exercise in humans, these conclusions are based on animal work.

Significant Acute Response of Brain-Derived Neurotrophic Factor Following a Session of Extreme Conditioning Program Is Correlated With Volume of Specific Exercise Training in Trained Men.

Several studies have demonstrated an acute and chronic increase of brain-derived neurotrophic factor (BDNF) in relation to different types of physical exercise. Currently, many individuals seek physical training strategies that present different types of stimulation and volume/intensity. Thus, the extreme conditioning methodology has gained great notoriety in the scientific and non-scientific environment. Knowing that BDNF values increase in an effort-dependent manner, it is necessary to study the effects of this strategy on BDNF levels. This study aimed to evaluate the acute response of BDNF in trained men submitted to an extreme conditioning program (ECP) session. Ten volunteers underwent an acute ECP session using the “as many reps as possible” (WOD-AMRAP) method, including three types of exercise (clean, wall ball and double or single-unders) for 9 min. BDNF was measured in the plasma, being collected baseline and immediately after the session. Total load of the clean exercise was five times greater than wall ball exercise (p < 0.05; 2096.1 ± 387.4 kg vs 415.8 ± 81.03 kg), which influenced little in the total load (p < 0.05, 2511.9 ± 358.52 kg) used. For the total volume, practitioners averaged 1.7 times more repetitions in the wall ball exercise compared to clean (46.2 ± 9 vs 29.5 ± 3.8 repetitions). The volunteers averaged 75.7 ± 12.6 double-unders repetitions, bringing the total volume of training to 151.4 ± 23.7 repetitions. Regarding the BDNF values, there was a significant difference (p = 0.05) between the pre- vs post-moments (11209.85 ± 1270.4 vs 12132.96 ± 1441.93 pg/ml). Effect size for this change as moderate (ES = 0.79). We found a positive correlation between total volume of clean exercise and delta BDNF values (p = 0.049). In conclusion, a single extreme conditioning session, through the practice of the WOD-AMRAP method, is capable of increasing the acute concentrations of plasma BDNF. In practical terms, we may suggest that future studies evaluate the effect of ECP as a strategy in the treatment of disorders associated with central degenerative changes.

Response of brain-derived neurotrophic factor to combining cognitive and physical exercise

Purpose: Brain-derived neurotrophic factor (BDNF) is well known for its potential to promote brain plasticity. It has been proposed that combining cognitive and physical exercise (CCPE) may have the potential to generate more synergistic benefits in cognitive function than either cognitive exercise (CE) or physical exercise (PE) alone. The purpose of this study was to examine acute responses of peripheral BDNF levels and cognitive performance to CE, PE, and CCPE.Methods: Thirteen healthy adult men participated in four experimental sessions; a 30-min CE, a 30-min cycling PE at an intensity of 60% peak oxygen uptake, a 30-min CCPE at the same intensity as PE, and a 30-min session of complete rest. Plasma BDNF levels and cognitive performance were measured before and after each session.Results: Both PE and CCPE significantly increased plasma BDNF levels (p < .05). CE led to no significant increase (p ≥ .05), and there was no significant difference in peripheral BDNF levels between PE and CCPE (p ≥ .05). No session induced a significant change in cognitive performance (p ≥ .05).Conclusions: Our study suggests that CE and PE have different responses of peripheral BDNF levels and that CCPE had no additional or synergistic effect on peripheral BDNF levels compared with PE alone. This study offers further insights into the potential mechanisms underlying the respective roles of CE, PE, and CCPE for peripheral BDNF levels and cognitive performance.

Exercise and circulating BDNF: Mechanisms of release and implications for the design of exercise interventions.

Engagement in regular bouts of exercise confers numerous positive effects on brain health across the lifespan. Acute bouts of exercise transiently improve cognitive function, while long-term exercise training stimulates brain plasticity, improves brain function, and helps to stave off neurological disease. The action of brain-derived neurotrophic factor (BDNF) is a candidate mechanism underlying these exercise-induced benefits and is the subject of considerable attention in the exercise-brain health literature. It is well established that acute exercise increases circulating levels of BDNF and numerous studies have sought to characterize this response for the purpose of improving brain health. Despite the interest in BDNF responses to exercise, little focus has been given to understanding the sources and mechanisms that underlie this response for the purpose of deliberately increasing circulating levels of BDNF. Here we review evidence to support that exploiting these mechanisms of BDNF release can help to optimize brain plasticity outcomes via exercise interventions, which could be especially relevant in the context of multimodal training (i.e., exercise and cognitive stimulation). Therefore, the purpose of this paper is to review the candidate sources of BDNF during exercise and the mechanisms of release. As well, we discuss strategies for maximizing BDNF responses to exercise, and propose novel research directions for advancing our understanding of these mechanisms.

Effect Of Acute High-Intensity Interval Exercise Vs. Continuous Moderate-Intensity Exercise On The BDNF, Lactate, And Cortisol Responses In Obese Individuals

PURPOSE: Obesity may attenuate the expression of brain-derived neurotrophic factor (BDNF), thereby increasing the risk of cognitive dysfunction. High-intensity interval exercise (HIIE) has been shown to be as or more effective than continuous moderate exercise (CME) in promoting the expression of BDNF in normal weight individuals. Therefore, the purpose of this study was to compare the effect of acute HIIE and CME on BDNF expression in obese individuals. METHODS: Twelve male subjects (6 obese and 6 normal-weight) participated in a randomized and caloric equated experiment: HIIE (30 minutes, 4 intervals of 4 minutes at 80% - 90% of VO2max with 3 minutes rest between intervals) and CME (38 minutes at 50% - 60% VO2max). Blood samples were collected for measurements of serum BDNF, blood lactate, and plasma cortisol prior to and following exercise. RESULTS: The BDNF response to acute HIIE was greater than CME in obese subjects when compared to normal-weight subjects. Similarly, although acute HIIE induced greater lactate and cortisol levels than CME, obese subjects produced less lactate, but no difference in cortisol than normal-weight subjects. CONCLUSIONS: Acute HIIE may be an effective protocol to upregulate BDNF expression in an obese population, independent of increased lactate and cortisol levels.

Impact of high intensity interval exercise on executive function and brain derived neurotrophic factor in healthy college aged males

BackgroundPrefrontal cortex (PFC)-dependent executive function is enhanced immediately following high intensity interval exercise (HIIE). Brain-derived neurotrophic factor (BDNF) is considered a biomarker associated with enhanced execute functioning capacity at rest and in response to exercise. However, the mechanisms responsible for the acute exercise-induced BDNF response in plasma and serum differ, and it is likely that the utilization of BDNF in plasma and/or serum as a biomarker of improved executive function following HIIE may be limited. Therefore, this study examined the impact of HIIE on the plasma and serum BDNF response to understand the efficaciousness of BDNF as a peripheral biomarker associated with improvements in PFC-dependent executive function. Thirteen healthy males (age: 23.62 ± 1.06 years) participated in a randomized, counterbalanced study, performing the Wisconsin Card Sorting Task (WCST) immediately following a 5-minute seated rest (control) and participation in a HIIE protocol administered two weeks apart. HIIE consisted of ten maximal bouts of all out pedaling on a cycle ergometer for 20 s (separated by 10 s of active recovery) against 5.5% of the subject's body weight. Whole blood was collected for the assessment of BDNF in both plasma and serum. Compared to the control session, HIIE elicited significant improvements in WCST performance, yet improvements in PFC-dependent executive function were independent of BDNF concentrations in plasma and serum. Results from this investigation demonstrate that a single session of low-volume, supramaximal HIIE significantly increases PFC-dependent executive function, thereby providing additional evidence to support the powerful benefits on HIIE on cognitive functioning.

A multifaceted investigation into the effects of acute exercise on indices of brain function.

Participation in regular exercise is important for the maintenance and improvement of brain health across the lifespan. These beneficial effects are realized almost immediately, as a single bout of exercise transiently improves cognitive function after cessation from exercise. This postexercise time period represents an opportunity to strategically prescribe cognitively stimulating activities for enhancing brain plasticity and function. Mechanistically, acute exercise is proposed to upregulate brain-derived neurotrophic factor (BDNF) expression and increase regional activation and arousal of brain areas involved in cognitive control; however, the specific mechanisms underlying this facilitation are poorly understood. The purpose of this study was to (i) investigate BDNF responses to small muscle mass exercise to probe a potential mechanism of BDNF release during exercise; (ii) create and validate an equipment-free exercise protocol for use in a magnetic resonance imaging (MRI) scanner, with the eventual goal of investigating brain responses during exercise that may underlie improved cognition; and (iii) determine the effect of a very brief bout of high-intensity interval exercise (HIIE) on neuroelectric indices of reinforcement learning in young adults. Serum BDNF, platelet, and the amount of BDNF per platelet responses were measured following short-duration, maximal effort and long-duration, submaximal effort forearm handgrip exercise. We assessed the magnitude and reliability of metabolic responses to a novel whole-body isometric contraction (WBI) exercise protocol. We also characterized the amount of head movement created by WBI. The event-related potential component associated with reward-based learning was assessed before and after a bout of HIIE. Forearm handgrip exercise significantly increased serum BDNF, platelets, and BDNF per platelet, suggesting the possibility of splenic and cellular contribution of BDNF in response to handgrip exercise. WBI reliably evokes metabolic responses that are similar in magnitude to previous in-MRI studies, and creates head movement suitable for MRI scanning. HIIE abolishes neuroelectric indices of reward learning, likely owing to incomplete recovery from exercise. These findings advance our understanding of neurochemical and neuroelectric responses to acute exercise and introduce a novel tool that stands to further elucidate the regional brain responses to exercise that may underlie enhanced cognition after exercise.

Altered prepulse inhibition of the acoustic startle response in BDNF-deficient mice in a model of early postnatal hypoxia: implications for schizophrenia

The brain-derived neurotrophic factor (BDNF) is a major proliferative agent in the nervous system. Both BDNF-deficiency and perinatal hypoxia represent genetic/environmental risk factors for schizophrenia. Moreover, a decreased BDNF response to birth hypoxia was associated with the disease. BDNF expression is influenced by neuronal activity and environmental conditions such as hypoxia. Thus, it may partake in neuroprotective and reparative mechanisms in acute or chronic neuronal insults. However, the interaction of hypoxia and BDNF is insufficiently understood and the behavioral outcome unknown. Therefore, we conducted a battery of behavioral tests in a classical model of chronic early postnatal mild hypoxia (10% O2), known to significantly impair brain development, in BDNF-deficient mice. We found selective deficits in measures associated with sensorimotor gating, namely enhanced acoustic startle response (ASR) and reduced prepulse inhibition (PPI) of ASR in BDNF-deficient mice. Unexpectedly, the alterations of sensorimotor gating were caused only by BDNF-deficiency alone, whereas hypoxia failed to evoke severe deficits and even leads to a milder phenotype in BDNF-deficient mice. As deficits in sensorimotor gating are present in schizophrenia and animal models of the disease, our results are of relevance regarding the involvement of BDNF in its pathogenesis. On the other hand, they suggest that the effect of perinatal hypoxia on long-term brain abnormalities is complex, ranging from protective to deleterious actions, and may critically depend on the degree of hypoxia. Therefore, future studies may refine existing hypoxia protocols to better understand neurodevelopmental consequences associated with schizophrenia.

Plasticity after pediatric cochlear implantation: Implication from changes in peripheral plasma level of BDNF and auditory nerve responses

IntroductionSensory neural hearing loss could lead to some structural and physiological changes in the auditory pathways, such as alteration in the expression of neurotrophins. These factors, especially Brain-Derived Neurotrophic Factor (BDNF), play an important role in synaptic functions and experience-related plasticity. Restoring cochlear function after hearing loss is possible through cochlear implantation (CI). Evaluation of the blood concentration changes of neurotrophins as prerequisites of plasticity could help scientists to determine the prognosis of CI as in the candidacy procedure or enhancing prosthesis function by adding the exact needed amount of BDNF to the electrode array. MethodsHere we have studied the plasma BDNF concentration before CI surgery and 6 months after using CI device in 15 pediatric CI recipients and compared this level with changes of BDNF concentration in 10 children who were using hearing aid (H.A). In addition, we searched for a possible correlation between post-surgery plasma BDNF concentration and electrical compound action potential (ECAP) and comfort-level (C-level) thresholds. ResultsPlasma BDNF concentration in children with CI increased significantly after CI surgery, while this difference in H.A group was not significant. Analysis of repeated measures of ECAP and C-level thresholds in CI group showed that there were some kinds of steadiness during follow- up sessions for ECAP thresholds in basal and E16 of middle electrodes, whereas C-level thresholds for all selected electrodes increased significantly up to six months follow-up. Interestingly, we did not find any significant correlation between post-surgery plasma BDNF concentration and ECAP or C-level threshold changes. ConclusionIt is concluded that changes in C-level threshold and steady state of ECAP thresholds and significant changes in BDNF concentration could be regarded as an indicator of experienced-related plasticity after CI stimulation.