Brain-derived Neurotrophic Factor Response Research Articles

Biomarker Responses to Acute Exercise and Relationship with Brain Blood Flow.

There is evidence that aerobic exercise is beneficial for brain health, but these effects are variable between individuals and the underlying mechanisms that modulate these benefits remain unclear. We sought to characterize the acute physiological response of bioenergetic and neurotrophic blood biomarkers to exercise in cognitively healthy older adults, as well as relationships with brain blood flow. We measured exercise-induced changes in lactate, which has been linked to brain blood flow, as well brain-derived neurotrophic factor (BDNF), a neurotrophin related to brain health. We further quantified changes in brain blood flow using arterial spin labeling. As expected, lactate and BDNF both changed with time post exercise. Intriguingly, there was a negative relationship between lactate response (area under the curve) and brain blood flow measured acutely following exercise. Finally, the BDNF response tracked strongly with change in platelet activation, providing evidence that platelet activation is an important mechanism for trophic-related exercise responses. Lactate and BDNF respond acutely to exercise, and the lactate response tracks with changes in brain blood flow. Further investigation into how these factors relate to brain health-related outcomes in exercise trials is warranted.

Mutation in the TRKB Cholesterol Recognition Site that blocks Antidepressant Binding does not Influence the Basal or BDNF-Stimulated Activation of TRKB

Brain-derived neurotrophic factor (BDNF) acting upon its receptor Neurotrophic tyrosine kinase receptor 2 (NTRK2, TRKB) plays a central role in the development and maintenance of synaptic function and activity- or drug-induced plasticity. TRKB possesses an inverted cholesterol recognition and alignment consensus sequence (CARC), suggesting this receptor can act as a cholesterol sensor. We have recently shown that antidepressant drugs directly bind to the CARC domain of TRKB dimers, and that this binding as well as biochemical and behavioral responses to antidepressants are lost with a mutation in the TRKB CARC motif (Tyr433Phe). However, it is not clear if this mutation can also compromise the receptor function and lead to behavioral alterations. Here, we observed that Tyr433Phe mutation does not alter BDNF binding to TRKB, or BDNF-induced dimerization of TRKB. In this line, primary cultures from embryos of heterozygous Tyr433Phe mutant mice (hTRKB.Tyr433Phe) are responsive to BDNF-induced activation of TRKB, and samples from adult mice do not show any difference on TRKB activation compared to wild-type littermates (TRKB.wt). The behavioral phenotype of hTRKB.Tyr433Phe mice is indistinguishable from the wild-type mice in cued fear conditioning, contextual discrimination task, or the elevated plus maze, whereas mice heterozygous to BDNF null allele show a phenotype in context discrimination task. Taken together, our results indicate that Tyr433Phe mutation in the TRKB CARC motif does not show signs of loss-of-function of BDNF responses, while antidepressant binding to TRKB and responses to antidepressants are lost in Tyr433Phe mutants, making them an interesting mouse model for antidepressant research.

An 840 kb distant upstream enhancer is a crucial regulator of catecholamine-dependent expression of the Bdnf gene in astrocytes.

Brain-derived neurotrophic factor (BDNF) plays a fundamental role in the developing and adult nervous system, contributing to neuronal survival, differentiation, and synaptic plasticity. Dysregulation of BDNF synthesis, secretion or signaling has been associated with many neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Although the transcriptional regulation of the Bdnf gene has been extensively studied in neurons, less is known about the regulation and function of BDNF in non-neuronal cells. The most abundant type of non-neuronal cells in the brain, astrocytes, express BDNF in response to catecholamines. However, genetic elements responsible for this regulation have not been identified. Here,we investigated four potential Bdnf enhancer regions and based on reporter gene assays, CRISPR/Cas9 engineering and CAPTURE-3C-sequencing we conclude that a region 840 kb upstream of the Bdnf gene regulates catecholamine-dependent expression of Bdnf in rodent astrocytes. We also provide evidence that this regulation is mediated by CREB and AP1 family transcription factors. This is the first report of an enhancer coordinating the transcription of Bdnf gene in non-neuronal cells.

The relationship between the brain-derived neurotrophic factor and neurocognitive response to physical exercise in individuals with schizophrenia

ObjectivePhysical exercise can improve neurocognition in individuals with schizophrenia, presumably by facilitating neuroplasticity. There is, however, large inter-individual variation in response. The brain-derived neurotrophic factor (BDNF) has been proposed to mediate these effects. The current aim was to investigate the sparsely studied relationship between peripheral resting BDNF and neurocognitive response to physical exercise in individuals with schizophrenia. MethodThe current study reports secondary analyses of data from a randomized controlled trial (RCT), ClinicalTrials.gov number 02205684, recently reported according to the CONSORT guidelines. Eighty-two individuals with schizophrenia (mean age 37 ± 14 years old, 61% men) were randomly allocated to high-intensity interval training (HIIT) or a comparison group performing low-intensity active video gaming (AVG). Both interventions consisted of 2 sessions/week for 12 weeks. In previously published primary RCT analyses, HIIT and AVG showed comparable small to moderate improvements in neurocognition. We now address the inter-individual variability in neurocognitive response. We apply mediation and moderation analyses for repeated measures designs (MEMORE) and mixed effects models. ResultsBaseline neurocognition was not significantly correlated with baseline levels of mature BDNF (baseline-mBDNF) or the precursor proBDNF. Nonetheless, baseline-mBDNF, but not baseline proBDNF, moderated the effect of exercise on neurocognition (p = 0.025) and explained 7% of the variance. The neurocognitive improvement increased with increasing baseline-mBDNF values. The moderating effect of baseline-mBDNF remained significant in a more complex model adding the moderating effects of exercise mode, sex, age, duration of illness and baseline VO2max on the outcome (neurocognition). Mean baseline-mBDNF significantly decreased from baseline to post-intervention (p = 0.036), regardless of exercise mode, differing by sex and associated with improved VO2max but not with change in neurocognition. A mediating role of mBDNF on the effect of physical exercise on neurocognition was not supported. Values of proBDNF mainly remained stable from baseline to post-intervention. ConclusionWe found that baseline-mBDNF moderated the effect of physical exercise on neurocognition in individuals with schizophrenia and explained a small part of the inter-individual variation in neurocognitive response. Mean mBDNF decreased from baseline to post-intervention, regardless of exercise mode. A mediating role of mBDNF on the effect of exercise on neurocognition was not supported. The inter-individual variation in neurocognitive response and the complex role of peripheral BDNF in physical exercise is still to be elucidated.

Effects of Antidepressant Medication on Brain-derived Neurotrophic Factor Concentration and Neuroplasticity in Depression: A Review of Preclinical and Clinical Studies

Depression is the most prevalent and debilitating disease with great impact on societies. Evidence suggests Brain-Derived Neurotrophic Factor (BDNF) plays an important role in pathophysiology of depression. Depression is associated with altered synaptic plasticity and neurogenesis. BDNF is the main regulatory protein that affects neuronal plasticity in the hippocampus. A wealth of evidence shows decreased levels of BDNF in depressed patients. Important literature demonstrated that BDNF-TrkB signaling plays a key role in therapeutic action of antidepressants. Numerous studies have reported antidepressant effects on serum/ plasma levels of BDNF and neuroplasticity which may be related to improvement of depressive symptoms. Most of the evidence suggested increased levels of BDNF after antidepressant treatment. This review will summarize recent findings on the association between BDNF, neuroplasticity, and antidepressant response in depression. Also, we will review recent studies that evaluate the association between postpartum depression as a subtype of depression and BDNF levels in postpartum women.

Effects of Antidepressant Medication on Brain-derived Neurotrophic Factor Concentration and Neuroplasticity in Depression: A Review of Preclinical and Clinical Studies.

Depression is the most prevalent and debilitating disease with great impact on societies. Evidence suggests Brain-Derived Neurotrophic Factor (BDNF) plays an important role in pathophysiology of depression. Depression is associated with altered synaptic plasticity and neurogenesis. BDNF is the main regulatory protein that affects neuronal plasticity in the hippocampus. A wealth of evidence shows decreased levels of BDNF in depressed patients. Important literature demonstrated that BDNF-TrkB signaling plays a key role in therapeutic action of antidepressants. Numerous studies have reported anti-depressant effects on serum/plasma levels of BDNF and neuroplasticity which may be related to improvement of depressive symptoms. Most of the evidence suggested increased levels of BDNF after antidepressant treatment. This review will summarize recent findings on the association between BDNF, neuroplasticity, and antidepressant response in depression. Also, we will review recent studies that evaluate the association between postpartum depression as a subtype of depression and BDNF levels in postpartum women.

Reinstatement of nicotine conditioned place preference in a transgenerational model of drug abuse vulnerability in psychosis: Impact of BDNF on the saliency of drug associations.

Psychotic disorders such as schizophrenia are often accompanied by high rates of cigarette smoking, reduced quit success, and high relapse rates, negatively affecting patient outcomes. However, the mechanisms underlying altered relapse-like behaviors in psychosis are poorly understood. The present study analyzed changes in extinction and reinstatement of nicotine conditioned place preference (CPP) and resulting changes in brain-derived neurotrophic factor (BDNF) in a novel heritable rodent model of psychosis, demonstrating increased dopamine D2 receptor sensitivity, to explore mechanisms contributing to changes in relapse-like behaviors. Male and female offspring of two neonatal quinpirole-treated (1mg/kg quinpirole from postnatal day (P)1-21; QQ) and two neonatal saline-treated (SS) Sprague-Dawley rats (F1 generation) were tested on an extended CPP paradigm to analyze extinction and nicotine-primed reinstatement. Brain tissue was analyzed 60min after the last nicotine injection for BDNF response in the ventral tegmental area (VTA), the infralimbic (IfL) and prelimbic (PrL) cortices. F1 generation QQ offspring demonstrated delayed extinction and more robust reinstatement compared to SS control animals. In addition, QQ animals demonstrated an enhanced BDNF response to nicotine in the VTA, IfL and Prl cortices compared to SS offspring. This study is the first to demonstrate altered relapse-like behavior in a heritable rodent model with relevance to comorbid drug abuse and psychosis. This altered pattern of behavior is hypothesized to be related to elevated activity-dependent BDNF in brain areas associated with drug reinforcement during conditioning that persists through the extinction phase, rendering aberrantly salient drug associations resistant to extinction and enhancing relapse vulnerability.

The potential beneficial effects of Lactobacillus plantarum GM11 on rats with chronic unpredictable mild stress- induced depression

ABSTRACT Objective The main purpose of the present study was to assess the beneficial effect of Lactobacillus plantarum GM11 (LacP GM11), screened from Sichuan traditional fermented food, in depressive rats induced by chronic unpredictable mild stress (CUMS). Methods Male SPF SD rats were randomly assigned to 3 groups: the control group, CUMS group and CUMS + LacP GM11 group (n = 10). The rats in the CUMS and LacP GM11 groups received CUMS stimulation for 42 d. The behavioral tests and levels of monoamine neurotransmitter, glucocorticoid hormone and brain-derived neurotrophic factor (BDNF) in the serum and hippocampus were measured. The effects of LacP GM11 on the mRNA and protein expression of BDNF and cAMP response element binding protein (CREB) in the hippocampus were also investigated. Results After supplementation for 21 d, LacP GM11 was associated with alleviation of depressive-like behavior, not anxiety-like behavior, in depressive rats. LacP GM11 increased the levels of 5-hydroxytryptamine (5-HT) and BDNF and decreased the level of cortisol (CORT) in the serum and hippocampus in depressed rats. In addition, treatment with LacP GM11 also increased the mRNA and protein expression of BDNF and CREB in the hippocampus. Conclusions This work has revealed that LacP GM11 has potential beneficial effects on depression. This effect might be related to alleviating monoamine neurotransmitter deficiency, HPA axis hyperfunction and CREB-BDNF signaling pathway downregulation. This study demonstrates that LacP GM11 could be a potential therapeutic approach to treat depression and other mental health problems.

Elevations in serum brain-derived neurotrophic factor following occupational heat stress are not influenced by age or common chronic disease

ABSTRACT With global warming, workers are increasingly exposed to strenuous occupations in hot environments. Given age- and disease-associated declines in thermoregulatory function, older workers are at an elevated risk of developing heat-related injuries. Brain-derived neurotrophic factor (BDNF) is thought to confer neuroprotection during acute exercise, however, the influence of environmental heat on BDNF responses during prolonged work remains unclear. Therefore, we evaluated serum BDNF concentrations before and after 180 min of moderate-intensity treadmill walking (200 W/m2) and after 60 min of post-exercise recovery in temperate (wet-bulb globe temperature (WBGT) 16°C) and hot (WBGT 32°C) environments in 13 healthy young men (mean [SD; 22 [3] years), 12 healthy older men (59 [4] years), 10 men with hypertension (HTN) (60 [4] years), and 9 men with type 2 diabetes (T2D) (60 [5] years). In the temperate condition, all but one participant (1 HTN) completed the 180 min of exercise. While exercise tolerance in the heat was lower in older men with HTN (117 min [45]) and T2D (123 min [42]) compared to healthy older men (159 min [31]) (both p ≤ 0.049), similar end-exercise rectal temperatures (38.9°C [0.4]) were observed across groups, paralleled by similar elevations in serum BDNF across groups at end-exercise (+1106 pg/mL [203]) and end-recovery (+938 pg/mL [146]; all p ≤ 0.01) in the heat. No changes in serum BDNF were observed in the temperate condition. Our findings indicate similar BDNF responses in individuals with HTN or T2D compared to their healthy counterparts, despite exhibiting reduced tolerance to heat.

Fasting for 20h does not affect exercise-induced increases in circulating BDNF in humans.

Intermittent fasting and exercise provide neuroprotection from age-related cognitive decline. A link between these two seemingly distinct stressors is their capability to steer the brain away from exclusively glucose metabolism. This cerebral substrate switch has been implicated in upregulating brain-derived neurotrophic factor (BDNF), a protein involved in neuroplasticity, learning and memory, and may underlie some of these neuroprotective effects. We examined the isolated and interactive effects of (1) 20-h fasting, (2) 90-min light exercise, and (3) high-intensity exercise on peripheral venous BDNF in 12 human volunteers. A follow-up study isolated the influence of cerebrovascular shear stress on circulating BDNF. Fasting for 20h decreased glucose and increased ketones (P≤0.0157) but had no effect on BDNF (P≥0.4637). Light cycling at 25% of peak oxygen uptake ( ) increased serum BDNF by 6 ± 8% (independent of being fed or fasted) and was mediated by a 7 ± 6% increase in platelets (P<0.0001). Plasma BDNF was increased from 336 pg l-1 [46,626] to 390 pg l-1 [127,653] by 90-min of light cycling (P=0.0128). Six 40-s intervals at 100% of increased plasma and serum BDNF, as well as the BDNF-per-platelet ratio 4- to 5-fold more than light exercise did (P≤0.0044). Plasma BDNF was correlated with circulating lactate during the high-intensity intervals (r=0.47, P=0.0057), but not during light exercise (P=0.7407). Changes in cerebral shear stress - whether occurring naturally during exercise or induced experimentally with inspired CO2 - did not correspond with changes in BDNF (P≥0.2730). BDNF responses to low-intensity exercise are mediated by increased circulating platelets, and increasing either exercise duration or particularly intensity is required to liberate free BDNF. KEY POINTS: Intermittent fasting and exercise both have potent neuroprotective effects and an acute upregulation of brain-derived neurotrophic factor (BDNF) appears to be a common mechanistic link. Switching the brain's fuel source from glucose to either ketone bodies or lactate, i.e. a cerebral substrate switch, has been shown to promote BDNF production in the rodent brain. Fasting for 20h caused a 9-fold increase in ketone body delivery to the brain but had no effect on any metric of BDNF in peripheral circulation at rest. Prolonged (90min) light cycling exercise increased plasma- and serum-derived BDNF irrespective of being fed or fasted and seemed to be independent of changes in cerebral shear stress. Six minutes of high-intensity cycling intervals increased every metric of circulating BDNF by 4 to 5 times more than prolonged low-intensity cycling; the increase in plasma-derived BDNF was correlated with a 6-fold increase in circulating lactate irrespective of feeding or fasting. Compared to 1 day of fasting with or without prolonged light exercise, high-intensity exercise is a much more efficient means to increase BDNF in circulation.

The modulation of Plasma Levels of Dopamine, Serotonin, and Brain-derived neurotrophic factor in response to variation in iron availability.

In the context of iron deficiency anemia, central dopamine, serotonin, and brain-derived neurotrophic factor (BDNF) are intensively investigated. However, peripheral isoforms are poorly investigated. This study aimed to investigate the modulation of plasma levels of dopamine, serotonin, and BDNF among children with iron deficiency anemia. A total of seventy-three iron-deficient (n=38) and iron-sufficient (n=35) children were included in the study. Twenty-nine subjects were showing clinical presentations and were diagnosed with iron deficiency anemia and forty-four were asymptomatic normal children. Plasma levels of dopamine, serotonin, and brain-derived neurotrophic factor were determined by enzyme-linked immunosorbent assay. As compared to corresponding levels among control subjects, Anemic subjects were having significantly higher plasma dopamine and lower plasma brain-derived neurotrophic factor levels. A significant linear and monotonic association of plasma dopamine and brain-derived neurotrophic factor with hemoglobin concentration (r=-0.520, P < 0.001 and ρ = 0.411, P = 0.001), respectively. Furthermore, there were significantly higher plasma serotonin levels among iron-deficient subjects with a significant inverse linear association with serum ferritin levels (r = -0.337, P = 0.005). Iron deficiency anemia is associated with the modulation of peripheral dopamine, serotonin, and brain-derived neurotrophic factor. Upregulation of dopamine and downregulation of brain-derived neurotrophic factor are correlated to the anemic status. The upregulation of plasma serotonin levels is iron-dependent and, probably, is attributed to the impairment of its metabolic fate. Further investigation is required to explore the pathophysiological and clinical association of these peripheral biomolecules in the context of iron deficiency anemia. (www.actabiomedica.it).

Acute submaximal exercise does not impact aspects of cognition and BDNF in people with spinal cord injury: A pilot study.

To investigate the effect of acute submaximal exercise, based on the spinal cord injury (SCI) Exercise Guidelines, on cognition and brain-derived neurotrophic factor (BDNF) in people with SCI. Eight adults (7 males) with traumatic SCI volunteered in this pre-registered pilot study. In randomized order, participants completed submaximal intensity arm cycling (60% of measured peak-power output at 55-60 rpm) for 30 min or time-matched quiet rest (control condition) on separate days. Blood-borne BDNF was measured in serum and plasma at pre-intervention, 0 min and 90 min post-intervention. Cognition was assessed using the Stroop Test and Task-Switching Test on an electronic tablet pre- and 10 min post-intervention. Submaximal exercise had no effect on plasma [F(2,12) = 1.09; P = 0.365; η² = 0.069] or serum BDNF [F(2,12) = 0.507; P = 0.614; η² = 0.024] at either 0 min or 90 min post-intervention. Similarly, there was no impact of exercise on either Stroop [F(1,7) = 2.05; P = 0.195; η² = 0.065] or Task-Switching performance [F(1,7) = 0.016; P = 0.903; η² < 0.001] compared to the control condition. Interestingly, there was a positive correlation between years since injury and resting levels of both plasma (r = 0.831; P = 0.011) and serum BDNF (r = 0.799; P = 0.023). However, there was not relationship between years since injury and the BDNF response to exercise. Acute guideline-based exercise did not increase BDNF or improve aspects of cognition in persons with SCI. This work establishes a foundation for continued investigations of exercise as a therapeutic approach to promoting brain health among persons with SCI.

Interleukin-6, undercarboxylated osteocalcin, and brain-derived neurotrophic factor responses to single and repeated sessions of high-intensity interval exercise

ObjectivesThe purpose of this study was to compare the effects of a single session of high-intensity interval exercise (HIIE) with 2 consecutive HIIEs, separated by 3 h of recovery, on plasma interleukin-6 (IL-6), undercarboxylated osteocalcin (ucOC), and brain-derived neurotrophic factor (BDNF) responses. MethodsTwenty male recreational endurance athletes completed two HIIE trials in a randomized crossover design: a single session of HIIE on the single exercise day (HIIE-S) and two sessions of HIIE 3 h apart on the double exercise day (HIIE-D). The HIIE protocol consisted of 10 × 1 min cycling at 100 % of peak oxygen uptake, with 75 s of low-intensity cycling at 60 W. Blood samples were collected to analyze IL-6, ucOC, and BDNF levels before and immediately after HIIE on the HIIE-S and before and immediately after the second HIIE on the HIIE-D. ResultsBoth HIIE interventions significantly increased (p < 0.001) plasma IL-6 (HIIE-S 33.90 % vs HIIE-D 31.04 %; p = 0.64), ucOC (HIIE-S 37.18 % vs HIIE-D 39.54 %; p = 0.85), and BDNF levels (HIIE-S 236.01 % vs HIIE-D 216.68 %; p = 0.69), with no group effect. ConclusionsOur results demonstrate that performing two consecutive HIIEs on the same day with a 3-h rest results in similar changes in plasma levels of IL-6, BDNF, and ucOC compared with a single session of HIIE.

Time-course effects of functional fitness sessions performed at different intensities on the metabolic, hormonal, and BDNF responses in trained men

BackgroundTo investigate the time-course effects of a self-regulated training session (performed at an rating perceived exertion of 6/10), all-out session, and a control session on the metabolic, hormonal, and brain derived neurotrophic factor (BDNF) responses in Functional-Fitness (FFT) participants.MethodsIn a randomized, crossover fashion, eight healthy males (age 28.1 ± 5.4 years old; body mass 77.2 ± 4.4 kg; VO2max: 52.6 ± 4.6 mL.(kg.min)−1; 2000 m rowing test 7.35 ± 0.18 min; 1RM back squat 135.6 ± 21.9 kg) performed a FFT session under two different conditions: all-out, or with the intensity controlled to elicit an rating perceived exertion (RPE) of 6 in the Borg 10-point scale (RPE6). A control session (no exercise) was also completed. Metabolic (lactate and creatine kinase), hormonal (testosterone and cortisol), and BDNF responses were assessed pre, post-0 h, 1 h, 2 h and 24 h after the sessions.ResultsCreatine kinase concentrations were significantly higher (p ≤ 0.05) after 24 h for both training sessions. Total and free testosterone concentrations were lower post-2 h for all-out when compared to the RPE6 session (p ≤ 0.05). Serum cortisol concentration increased post-0 h (p = 0.011) for RPE6 and post-0 h (p = 0.003) and post-1 h (p = 0.030) for all-out session when comparing to baseline concentrations. BDNF was significantly higher (p = 0.002) post-0 h only for the all-out session when compared to baseline. A positive correlation between blood lactate concentrations and BDNF (r = 0.51; p = 0.01) was found for both effort interventions.ConclusionsA single FFT session when performed in all-out format acutely increases the concentrations of serum BDNF. However, physiological stress markers show that the all-out session requires a longer recovery period when compared to the RPE6 protocol. These findings can be helpful to coaches and practitioners design FFT session.

Regional Differences in BDNF Expression and Behavior as a Function of Sex and Enrichment Type: Oxytocin Matters.

The early environment is critical to brain development, but the relative contribution of physical versus social stimulation is unclear. Here, we investigated in male and female rats the response to early physical and social environmental enrichment in relation to oxytocin (OT) and brain-derived neurotrophic factor (BDNF) expression. The findings show that males and females respond differently to prolonged sensorimotor stimulation from postnatal days 21-110 in terms of functional, structural, and molecular changes in the hippocampus versus medial prefrontal cortex (mPFC). Physical enrichment promoted motor and cognitive functions and hippocampal BDNF mRNA and protein expression in both sexes. Combined physical and social enrichment, however, promoted functional and structural gain in females. These changes were accompanied by elevated plasma oxytocin (OT) levels and BDNF mRNA expression in the mPFC, while the hippocampus was not affected. Administration of an OT antagonist in females blocked the beneficial effects of enrichment and led to reduced cortical BDNF signaling. These findings suggest that an OT-based mechanism selectively stimulates a region-specific BDNF response which is dependent on the type of experience.

Dietary Macronutrients Do Not Differently Influence Postprandial Serum and Plasma Brain-Derived Neurotrophic Factor Concentrations: A Randomized, Double-Blind, Controlled Cross-Over Trial.

Objectives: Brain-derived neurotrophic factor (BDNF) plays a role in cognition and metabolism. Specific nutrients can affect fasting BDNF concentrations, which are potentially mediated by insulin and/or glucose. Since macronutrients trigger each a different insulin and glucose response, we examined postprandial effects of meals rich in fat, carbohydrates, or protein on BDNF concentrations. BDNF was analyzed in serum and plasma, since concentration differences can be found between matrices.Methods: Healthy overweight/obese male participants (n = 18) participated in this randomized, double-blind, cross-over trial consisting of three test days with 1 week wash-out periods. Either a high-fat (En% fat, carbohydrates, protein: 52.3, 39.2, 8.0), high-carbohydrate (En% 9.6, 81.5, 8.6) or high-protein meal (En% 10.6, 51.5, 36.9) was consumed on each test day. BDNF concentrations were measured after 0, 60, and 240 min. Glucose and insulin concentrations were measured after 0, 15, 30, 45, 60, 90, 120, and 240 min.Results: BDNF concentrations were higher in serum compared with plasma (P < 0.001). Postprandial BDNF concentrations in serum decreased significantly after the high-fat (P = 0.013) and high-carbohydrate meals (P = 0.040), and showed a trend after the high-protein meal (P = 0.076). No differences were found between meals (P = 0.66). Postprandial BDNF concentrations measured in plasma did not significantly change after the different meals (P = 0.47). As total area under the curve (AUC) for glucose was significantly higher after the high-carbohydrate meal compared with the high-fat (P = 0.003) and high-protein meals (P < 0.001), and the total AUC for insulin was higher after the high-carbohydrate (P < 0.001) and high-protein meals (P < 0.001) compared with the high-fat meal, it seems that acute changes in glucose and insulin do not affect postprandial BDNF concentrations. However, after the high-protein meal, the higher total AUC for glucose correlated with lower serum BDNF concentrations, and a higher maximal increase in glucose correlated with a lower maximal increase in plasma BDNF concentrations. There were no correlations with insulin concentrations after either meal.Conclusion: Serum BDNF concentrations were higher than plasma concentrations. Since postprandial BDNF responses were not different between the meals, we conclude that there is no role for insulin or glucose in regulating postprandial BDNF concentrations.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03139890].

Serum and plasma brain-derived neurotrophic factor concentration are elevated by systemic but not local passive heating.

Brain-derived neurotrophic factor (BDNF) plays a key role in neuronal adaptations. While previous studies suggest that whole-body heating can elevate circulating BDNF concentration, this is not known for local heating protocols. This study investigated the acute effects of whole-body versus local passive heating on serum and plasma BDNF concentration. Using a water-perfused suit, ten recreationally active males underwent three 90 min experimental protocols: heating of the legs with upper-body cooling (LBH), whole-body heating (WBH) and a control condition (CON). Blood samples were collected before, immediately after and 1 h post-heating for the determination of serum and plasma BDNF concentration, platelet count as well as the BDNF release per platelet. Rectal temperature, cardiac output and femoral artery shear rate were assessed at regular intervals. Serum and plasma BDNF concentration were elevated after WBH (serum: 19.1±5.0 to 25.9±11.3 ng/ml, plasma: 2.74±0.9 to 4.58±2.0; p<0.044), but not LBH (serum: 19.1±4.7 to 22.3±4.8 ng/ml, plasma: 3.25±1.13 to 3.39±0.90 ng/ml; p>0.126), when compared with CON (serum: 18.6±6.4 to 16.8±3.4 ng/ml, plasma: 2.49±0.69 to 2.82±0.89 ng/ml); accompanied by an increase in platelet count (p<0.001). However, there was no change in BDNF content per platelet after either condition (p = 0.392). All physiological measures were elevated to a larger extent after WBH compared with LBH (p<0.001), while shear rate and rectal temperature were higher during LBH than CON (p<0.038). In conclusion, WBH but not LBH acutely elevates circulating BDNF concentration. While these findings further support the use of passive heating to elevate BDNF concentration, a larger increase in shear rate, sympathetic activity and/or rectal temperature than found after LBH appears needed to induce an acute BDNF response by passive heating.

Effects of Padel Competition on Brain Health-Related Myokines

Padel is becoming one of the most widespread racket sports that may have potential health benefits. Considering that several myokines mediate the cross-talk between skeletal muscles and the brain, exerting positive effects on brain health status, this study was designed to evaluate the responses of brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), and irisin (IR) to padel competition in trained players and to determine whether these responses were sex-dependent. Twenty-four trained padel players (14 women and 10 men with a mean age of 27.8 ± 6.3 years) participated voluntarily in this study. Circulating levels of BDNF, LIF, and IR were assessed before and after simulated padel competition (real playing time, 27.8 ± 8.49 min; relative intensity, 75.2 ± 7.9% maximum heart rate). Except for BDNF responses observed in female players (increasing from 1531.12 ± 269.09 to 1768.56 ± 410.75 ng/mL), no significant changes in LIF and IR concentrations were reported after padel competition. In addition, no sex-related differences were found. Moreover, significant associations between IR and BDNF were established at both pre- and post-competition. Our results suggest that while competitive padel practice stimulates BDNF response in female players, padel competition failed to boost the release of LIF and IR. Future studies are needed to further explore the role of these exercise-induced myokines in the regulation of brain functions and to identify the field sports that can contribute to myokine-mediated muscle–brain crosstalk.

Acute Effects of High-Intensity Interval Training on Brain-Derived Neurotrophic Factor, Cortisol and Working Memory in Physical Education College Students.

High-intensity interval training (HIIT) is considered one of the most effective methods for improving cardiorespiratory and metabolic functions. However, it is necessary to clarify their effects on neurophysiological responses and coginitive functioning. Thus, this study aimed to determine the effects of an acute bout of HIIT on neurocognitive and stress-related biomarkers and their association with working memory (WM) capacity in healthy young adults. Twenty-five male college students performed a single bout of HIIT consisting of 10 × 1 min of cycling at their VO2 peak power output. Plasma Brain-Derived Neurotrophic Factor (BDNF) and cortisol (CORT) levels, and WM (Digit Span Test (DST)), were assessed pre-, post- and 30 min post-intervention. Significant post-exercise increases in circulating BDNF and CORT levels were observed coinciding with the highest DST performance; however, no statistical associations were found between cognitive and neurophysiological variables. Moreover, DST scores obtained 30 min after exercise remained higher than those assessed at pre-exercise. In conclusion, the stress induced by a single bout of HIIT induces a remarkable response of BDNF and CORT boosting WM capacity in healthy young males. Future research should clarify the association between cognitive and neurobiological markers during intense exercise stimulation.

Acute Systemic Response Of BDNF, Lactate and Cortisol to Strenuous Exercise Modalities in Healthy Untrained Women.

Acute bouts of intense exercise increase lactate concentration, which in turn stimulates brain-derived neurotrophic factor (BDNF) production. Cortisol released during intense exercise might inhibit BDNF synthesis. This study examined the acute effects of 2 protocols of strenuous exercise on serum BDNF. Seventeen physically-active healthy females (Age = 20.0 ± 0.9 yr., BMI = 23.0 ± 2.6 kg/m2) performed a strenuous cycle-ergometer graded exercise test (GXT) and a high-intensity interval training session (HIIT). Serum BDNF, serum cortisol, cortisol: BDNF ratio and blood lactate (BLa) were recorded at baseline and immediately following exercise. Although non-statistically significant, the HIIT session elicited a higher magnitude of change from baseline for BDNF (d = 0.17) and cortisol (d = 1.18) than after the GXT (d = -0.26, and d = 0.82, respectively). An interaction was found between GXT and HIIT trials and measurements on BLa levels, with higher post-exertion values after HIIT than after GXT (p < 0.0001, η2 = 0.650, 95%CI = 2.2, 5.2). The higher BLa levels did not raise circulating BDNF. The elevated cortisol levels may have overcome the effects of lactate on BDNF. However, the higher BLa induced by HIIT suggest that interval exercise modality on the long-term could be a feasible intervention to increase circulating peripheral BDNF, at least in untrained healthy women.