Changes In Brain-derived Neurotrophic Factor Research Articles

Changes In Brain-Derived Neurotrophic Factor Are Correlated With Changes In Il-6 During Aerobic Exercise.

The effects of exercise on inflammation are complex. Literature suggests a reduction of chronic inflammation following exercise training, however, following acute bouts of exercise, both pro- and anti- inflammatory responses have been demonstrated. Brain-derived neurotrophic factor (BDNF) has been suggested to have an intermediary role during the inflammatory response to exercise. Therefore, observing the role of BDNF in the post-exercise inflammatory response may allow for a greater understanding of the intricacies of the inflammatory response. PURPOSE: The purpose of this study was to observe the relationship between BDNF and interleukin-6 (IL-6) during aerobic exercise in different environmental conditions. METHODS: Six college aged men (26 ± 3 yrs) completed a VO2max test (48.6 ± 5.7 mL/kg-1/min-1) along with three separate trials in 5°C (LT), 220C (MT), and 35°C (HT). Each trial consisted of cycling for 60 minutes at 60% VO2max, a time to exhaustion trial at 90% VO2max (TTE), and passive recovery for 60 min in the same condition. Blood was obtained before exercise (PRE), after 60 min of cycling (60), after the TTE (90), and after recovery (REC). Blood was analyzed via ELISA for serum and plasma BDNF concentrations and serum IL-6 concentrations. Change scores were calculated as percentages (ΔPRE to 60; ΔPRE to 90; ΔPRE to REC) and analyzed using a Pearson Correlation, with significance defined as α ≥ 0.05. RESULTS: Changes in serum IL-6 (ΔPRE to 60) were significantly (r = .566, p = 0.018) correlated to changes in plasma BDNF (ΔPRE to 60). Changes in serum IL-6 (ΔPRE to 90) were significantly (r = 0.511, p = 0.043) correlated to changes in serum BDNF (ΔPRE to 90). Changes in serum BDNF were not significantly correlated to changes in plasma BDNF. No other significant correlations were observed. CONCLUSION: This study suggests there is a relationship between IL-6 and BDNF. This could lead to better understanding of the mechanism for both IL-6 and BDNF responses due to aerobic exercise. The insignificant correlation between serum and plasma BDNF give evidence that each may represent different pools of BDNF that respond independently to aerobic exercise. This study was partially funded by the Kent State University Research Council

Acute Resistance Exercise Elicits Bdnf But Not Cathepsin B In Well-trained Men

PURPOSE: The aim of this study was to examine if multi-joint RE exercises (back squat, bench press, and deadlift) to volitional failure elicited a circulating response of biomarkers associated with neuroprotection and if differences in biomarker changes existed between exercises. Further, we examined if the pre- to post-exercise changes in BDNF and IL-6 were related. METHODS: Thirteen males (age: 24.5±3.8yrs, body mass: 84.01±15.44kg, height: 173.43±8.57cm, training age: 7.1±4.2yrs) performed 4 sets to failure at 80% of a one-repetition maximum (1RM) on the squat, bench press, and deadlift in successive weeks. The bench press was always performed second and the order of the squat and deadlift was counterbalanced. The measured biomarkers are brain derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), cathepsin B (CatB), and interleukin 6 (IL-6). Biomarkers were assessed immediately pre- and post-exercise. RESULTS: There was a main time effect (p<0.01) for BDNF. In the deadlift (p=0.01) and bench press (p=0.01) conditions BDNF significantly increased, however, no significant change was observed the squat condition (p=0.21). There was a main time effect (p<0.01) for IL-6 with a significant increase in the squat (p<0.01), but not the bench press (p=0.88) and deadlift conditions (p=0.24). No main time effect was observed for either CatB (p=0.62) or IGF-1 (p=0.56). No significant correlations were observed between the acute change in BDNF and IL-6 (p>0.05), however, this relationship was nearly significant in the deadlift condition (p=0.058). CONCLUSION: In summary, acute multi-joint RE elicits a significant increase in circulating BDNF. This investigation is the first to report the lack of a transient change of CatB to an acute RE protocol.

Submaximal Exercise Does Not Increase Brain-Derived Neurotrophic Factor (BDNF) In People With Spinal Cord Injury

Brain-derived neurotrophic factor (BDNF) has been implicated in repair and regeneration of peripheral neurons, and is important for brain health. Acute exercise (EX) increases circulating BDNF in an intensity dependent manner in able-bodied individuals. However, the response of BDNF to EX in people with spinal cord injury (SCI) is poorly understood. PURPOSE: to investigate the hypothesis that submaximal EX will increase serum and plasma BDNF in people with SCI. METHODS: Nine adults with SCI participated (M age = 39.2 ± 11.0 years; M years post-injury = 16.5 ± 9.2). After completing a maximal exercise test on an electromagnetically braked arm-crank ergometer to determine peak power output (PPO), participants completed two visits in randomized order: 1) submaximal EX (30 minutes maintaining 55-65 rpm @ 60% PPO); and 2) seated control (CTL). Ratings of perceived exertion (RPE) were measured during EX using the 6-20 visual Borg RPE scale. Heart rate (HR) and blood pressure (BP) were measured pre- and post-EX. BDNF was measured via ELISA in both serum and plasma from venous blood sampled at pre-, post-, and 90 min post-EX. For the CTL visit, participants rested quietly for 120 min and blood was sampled at equivalent time points to EX. A 2-factor repeated measures ANOVA was computed to assess BDNF responses by time and condition. Paired t-tests were computed to assess HR and BP responses to EX. Pearson correlations were computed to explore relationships between BDNF and physiological responses to EX and work rate. RESULTS: The average EX work rate was 47 ± 17 W and RPE was 13 ± 1. HR increased by 26 ± 33 bpm (+41%; p=0.059), whereas systolic and diastolic BP remained unchanged after EX. Contrary to our hypotheses, EX had no effect on serum (Pre vs. Post-EX = 22447.9 ± 9071.1 pg/mL vs. 26552.8 ± 6563.4 pg/mL; F(1,12) = 0.51, p=0.53) or plasma (Pre vs. Post-EX = 1802.7 ± 1031.1 vs. 1662.7 ± 1390.0 pg/mL; F(1,10) = 0.77, p=0.45) BDNF. Exploratory correlational analyses showed no relationships between changes in BDNF and the outlined parameters. CONCLUSIONS: Submaximal EX did not increase BDNF in people with SCI. Future studies should systematically investigate BDNF responses to higher EX intensities given the intensity-dependent response in able-bodied people. FUNDING: Rick Hansen Foundation through the Blusson Integrated Cures Partnership.

Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: A randomized, double-blind, placebo-controlled trial.

This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment. We evaluated the effects of melatonin on cognition, depressive symptoms and sleep quality, and whether these effects were related to serum levels of Brain Derived Neurotrophic Factor (BDNF) and its receptor, tropomyosin kinase B (TrkB). Thirty-six women were randomly assigned to receive melatonin or placebo for 10 days. To evaluate cognitive performance, we used the Trail-Making-Test Parts A and B (A-B), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and an inhibitory task type Go / No-Go. Our results revealed that melatonin improved executive function on TMT scores, enhanced episodic memory (immediate and delayed) and recognition on RAVLT, and increased verbal fluency in the orthographic COWAT. The TMT-A-B(A-B) were negatively correlated with baseline levels of TrkB and BDNF, respectively. At the end of treatment, changes in TrkB and BDNF were inversely associated with depressive symptoms and sleep quality, but not with the TMT scores. These results suggest a neuroprotective effect of melatonin to counteract the adverse effects of ACBC on cognitive function, sleep quality and depressive symptoms.

Brain-derived neurotrophic factor and glutathione peroxidase as state biomarkers in alcohol use disorder patients undergoing detoxification.

The pathophysiology of alcohol use disorder (AUD) is not totally clear. The aim of this study was to investigate the serum levels of brain-derived neurotrophic factor (BDNF) and oxidative stress markers in AUD patients during alcohol detoxification. Evaluation of changes in BDNF, glutathione peroxidase (GPX), catalase, superoxide dismutase, thiobarbituric acid reactive substances, 8-hydroxy 2’-deoxyguanosine, PCC and S100B were carried out.14 AUD inpatients and 20 healthy control subjects were recruited for this study. The serum BDNF, S100B and oxidative stress markers were measured with assay kits.Serum levels of catalase, GPX, PCC and 8-hydroxy 2’-deoxyguanosine were significantly higher in the AUD group subjects than in the controls (P < .05). However, BDNF levels were lower in the AUD group than in the controls (P < .05). After alcohol detoxification treatment, the GPX levels in the AUD group dropped (P < .05) and the BDNF levels rose (P < .05).The results suggest that serum BDNF and GPX levels might be state biomarkers for AUD patients undergoing alcohol detoxification.

Circulating Diabetic Candidate Neurotrophic Factors, Brain-Derived Neurotrophic Factor and Fibroblast Growth Factor 21, in Sleeve Gastrectomy

Recent studies show brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 21 (FGF21) are neurotrophic factors associated with obesity and diabetes mellitus (DM). Laparoscopic sleeve gastrectomy (LSG) can significantly reduce weight and improve DM. In this study, we enrolled 78 patients with obesity and evaluated the change of BDNF and FGF21 6 months after LSG. At baseline, the BDNF level was similar between the preoperative DM (n = 30) (17.1 ± 7.7 ng/ml) and non-DM (n = 48) (17.0 ± 6.9 ng/ml) patients with obesity, but FGF21 was significantly higher in the DM patients (201.5 ± 204.3 versus 107.6 ± 63.8 pg/ml). At 6 months after LSG, most of the preoperative DM patients (96.7%) had DM either resolved (66.7%) or improved (30%). BDNF increased and FGF21 decreased significantly regardless of the preoperative DM status, while FGF21 decreased more prominently in the preoperative DM patients (−92.6 ± 179.8 versus −4.6 ± 63.4 pg/ml). After adjusted for age, sex, and preoperative DM status, FGF21 became significantly and positively related to C-peptide (β = 18.887), insulin (β = 2.399), and homeostasis model assessment of insulin resistance index (β = 8.566) after surgery. In conclusion, diabetic patients with obesity had higher FGF21 and similar BDNF levels compared to non-diabetic obese patients. BDNF increased and FGF21 decreased significantly after LSG. FGF21 became positively associated with several insulin-related profiles after surgery.

Assessing BDNF as a mediator of the effects of exercise on depression

Brain-derived neurotrophic factor (BDNF) is associated with neuronal growth and reduced BDNF has been implicated in depression. A recent meta-analysis documented reliable effects of exercise on BDNF levels (Szuhany et al., 2015); although, few studies included participants with mental health conditions. In this study, we examine whether increased exercise was associated with enhanced BDNF response in depressed patients, and whether this change mediated clinical benefits. A total of 29 depressed, sedentary participants were randomized to receive either behavioral activation (BA) plus an exercise or stretching prescription. Blood was collected prior to (resting BDNF levels) and following an exercise test (pre-to post-exercise BDNF change) at four points throughout the study. Participants also completed depression and exercise assessments. BDNF increased significantly across all assessment points (p < 0.001, d = 0.83). Changes in BDNF from pre-to post-exercise were at a moderate effect for the interaction of exercise and time which did not reach significance (p = 0.13, d = 0.53), with a similar moderate, non-significant effect for resting BDNF levels (p = 0.20, d = 0.49). Contrary to hypotheses, change in resting BDNF or endpoint change in BDNF was not associated with changes in depression. In an intervention that included active treatment (BA), we could not verify an independent predictive effect for changes in BDNF across the trial. Overall, this study adds to the literature showing reliable effects of acute exercise on increasing BDNF and extends this research to the infrequently studied depressed population, but does not clarify the mechanism behind exercise benefits for depression. Clinical Trials Registry (clinicaltrials.gov)NCT02176408, “Efficacy of Adjunctive Exercise for the Behavioral Treatment of Major Depression”.

Brain‐derived neurotrophic factor and Glial cell line‐derived neurotrophic factor expressions in the trigeminal root entry zone and trigeminal ganglion neurons of a trigeminal neuralgia rat model

Microvascular compression on the trigeminal root entry zone (TREZ) is the main etiology of trigeminal neuralgia (TN) patients. To investigate brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in the trigeminal ganglion (TG) and TREZ, immunofluorescence staining and Western blot were used in a rat TN model. Both BDNF and GDNF were observed in the TG neurons and TREZ. The expression of the BDNF dimer in the TG was increased in the TN group, while GDNF expression was decreased after compression injury. The BDNF dimer/pro-BDNF ratio in the TREZ of the TN group was higher than that in the sham group, but the GDNF expression in the TREZ was significantly lower than that in the sham group. These results suggested that compression injury in the TREZ of rats induced dynamic changes in BDNF and GDNF in both the TG and TREZ, and these changes are involved in the nociceptive transmission of the TN animal model.

Early changes of serum BDNF and SSRI response in adolescents with major depressive disorder

BackgroundRecent evidence suggests that brain-derived neurotrophic factor (BDNF) levels and their early changes may predict antidepressant response in adults with major depressive disorder (MDD). However, in adolescents, BDNF levels in depression and their changes during antidepressant treatment are relatively unknown. We aimed to investigate whether pre-treatment BDNF levels and their early changes predict antidepressant response in depressed adolescents. MethodsThe study included 83 MDD adolescents and 52 healthy controls aged 12 to 17 years. All depressed adolescents were treated with escitalopram in an 8 week, open-label trial. Depression severity and serum BDNF level at baseline, and weeks 2 and 8 were measured with the Children's Depression Rating Scale-Revised (CDRS-R) and ELISA, respectively. ResultsResponders showed a significant decrease in BDNF levels at week 2 but non-responders and healthy controls had no changes in BDNF levels at week 2. The early decrease (baseline – week 2) of BDNF levels predicted SSRI response with moderate sensitivity and specificity. Logistic regression analysis revealed that early BDNF decrease predicted SSRI response at week 8 after controlling for other demographic and clinical variables. LimitationsThe follow-up duration of the study was limited in 8 weeks. It remains possible that serum BDNF levels would have changed with longer treatment. ConclusionsThis is the first longitudinal study to investigate the effect of antidepressants on BDNF levels in adolescents with MDD. Our findings suggest that a decrease of serum BDNF levels in early phase of SSRI treatment may be associated later SSRI response in adolescents with MDD.

Repeated hyperthermia exposure increases circulating Brain Derived Neurotrophic Factor levels which is associated with improved quality of life, and reduced anxiety: A randomized controlled trial

Hyperthermia is known to be beneficial to patients affected by various diseases. Brain Derived Neurotrophic Factor (BDNF) is a marker of neuroplasticity usually increased as response to acute exposure to human body stressors. Little is known about BDNF changes after repeated exposure to hyperthermia. To investigate the effect of a repeated hyperthermia exposure programme (HTC) on serum BDNF in healthy humans. Randomized, single-blind, controlled trial in healthy humans conducted at Sechenov University Physiology Laboratory between December 2016 and November 2018. The treatment period was 10 weeks. Researchers analysing serum BDNF and questionnaires data were blinded to participants allocation. Were 34 healthy male (age 20.2±1.6 years). Repeated Hyperthermia exposure programme, HTC, versus Light Intermittent Exercise, LIE, programme as control (10 weeks). Change in BDNF from baseline to final visit three days after treatment completion. 25 participants were analyzed. One participant withdrew before signing the informed consent and 8 participants (n=3 in HTC and n=5 in LIE) could not undertake the first assessment and were excluded. Mean change in BDNF was higher in HTC group vs LIE after both time points (after 12 and after 24 sessions). After 24 sessions BDNF was 30170 (SD 5268) pg/ml in HTC group a value that was significantly higher than 24104 (SD 2876) pg/ml measured in LIE group. BDNF concentrations were significantly higher than baseline values in HTC group only, 30170 (SD 5268) vs 26710 (SD 5437) pg/ml. A 10-week programme consisting of repeated exposure to hyperthermia resulted in a significantly higher increase of circulating BDNF compared to a programme consisting of intermittent light intensity exercise.

Testosterone replacement causes dose-dependent improvements in spatial memory among aged male rats

Testosterone has been shown to have dose-dependent effects on spatial memory in males, but the effects of aging upon this relationship remain unclear. Additionally, the mechanism by which testosterone regulates memory is unknown, but may involve changes in brain-derived neurotrophic factor (BDNF) within specific brain regions. We tested the effects of age and testosterone on spatial memory among male rats using two spatial memory tasks: an object-location memory task (OLMT) and the radial-arm maze (RAM). Castration had minimal effect on performance on the RAM, but young rats (2 months) performed significantly fewer working memory errors than aged rats (20 months), and aged rats performed significantly fewer reference memory errors. Both age and castration impaired performance on the OLMT, with only the young rats with intact gonads successfully performing the task. Subsequent experiments involved daily injections of either drug vehicle or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.00 mg/rat) given to castrated aged males. On the RAM, a low physiological dose (0.125 mg) and high doses (0.500–1.000 mg) of testosterone improved working memory, while an intermediate dose (0.250 mg) did not. On the OLMT, only the 0.250 mg T group showed a significant increase in exploration ratios from the exposure trials to the testing trials, indicating that this group remembered the position of the objects. Brain tissue (prefrontal cortex, hippocampus, and striatum) was collected from all subjects to assay BDNF. We found no evidence that testosterone influenced BDNF, indicating that it is unlikely that testosterone regulates spatial memory through changes in BDNF levels.

Impact of resistance training program configuration on the circulating brain-derived neurotrophic factor response.

This study examined the acute and resting changes of brain-derived neurotrophic factor (BDNF) and inteleukin-6 (IL-6) and if changes in these biomarkers were correlated during resistance training (RT). Fifteen men with ≥2 years of RT experience (age: 23 ± 3 years, body mass: 84.4 ± 12.3 kg) participated. Subjects performed RT 3×/week for 6 weeks in either a high-repetition (HR; n = 8) or low-repetition (LR; n = 7) group. Protocols during week 1 were HR - Monday: 4 (sets) × 12 (repetitions) at 60% of 1-repetition maximum, Wednesday: 4 × 10 at 65%, Friday: 5 × 8 at 70%; LR - Monday: 8 × 6 at 75%, Wednesday 9 × 4 at 80%, Friday: 10 × 2 at 85%. Total volume was equated for the 6 weeks but not for individual sessions. Greater volume and intensity were performed in LR versus HR (p < 0.01) on Mondays. Plasma was collected immediately before and after exercise of the Monday session. There were no significant interactions or main effects for BDNF (p > 0.05). There was a moderate between-group effect size (0.57) in favor of LR in week 6, suggesting a potentially greater acute increase in BDNF in LR versus HR. For IL-6, a statistically significant main effect was observed for training (p < 0.0001), showing an acute increase in IL-6 in both weeks (p < 0.01); however, no other 3-way or 2-way interactions existed (p > 0.05). A minimum volume threshold of RT may be needed to induce acute elevations in BDNF. Novelty A minimum RT volume threshold may be needed to elicit BDNF. A close proximity to failure may be needed to elicit BDNF. BDNF and IL-6 did not correlate.

Exercise Training Induced Changes In Nuclear Magnetic Resonance-Measured Lipid Particles In Mild Cognitively Impaired Elderly African American Volunteers: A Pilot Study.

PurposePoor cardiorespiratory fitness (CRF) is linked to cognitive deterioration, but its effects on lipid heterogeneity and functional properties in older African American (AA) subjects with mild cognitive impairment (MCI) need elucidation. This study determined whether exercise training-induced changes in blood lipid particle sizes (LPS) were associated with CRF determined by VO2Max in elderly AAs with MCI. Given the pivotal role of brain-derived neurotrophic factor (BDNF) on glucose metabolism, and therefore, “diabetic dyslipidemia”, we also determined whether changes in LPS were associated with the levels of serum BDNF.MethodsThis analysis included 17 of the 29 randomized elderly AAs with MCI who had NMR data at baseline and after a 6-month training. We used Generalized Linear Regression (GLM) models to examine cardiorespiratory fitness (VO2Max) effects on training-induced change in LPS in the stretch and aerobic groups. Additionally, we determined whether the level of BDNF influenced change in LPS.ResultsCollectively, mean VO2Max (23.81±6.17) did not differ significantly between aerobic and stretch groups (difference=3.17±3.56, P=0.495). Training-related changes in very low-density lipoprotein, chylomicrons, and total low-density lipoprotein (LDL) particle sizes correlated significantly with VO2Max, but not after adjustment for age and gender. However, increased VO2Max significantly associated with reduced total LDL particle size after similar adjustments (P = 0.046). While stretch exercise associated with increased protective large high-density lipoprotein particle size, the overall effect was not sustained following adjustments for gender and age. However, changes in serum BDNF were associated with changes in triglyceride and cholesterol transport particle sizes (P < 0.051).ConclusionPromotion of stretch and aerobic exercise to increase CRF in elderly AA volunteers with MCI may also promote beneficial changes in lipoprotein particle profile. Because high BDNF concentration may reduce CVD risk, training-related improvements in BDNF levels are likely advantageous. Large randomized studies are needed to confirm our observations and to further elucidate the role for exercise therapy in reducing CVD risk in elderly AAs with MCI.

The impact of physical exercise on cognitive and affective functions and serum levels of brain-derived neurotrophic factor in nursing home residents: A randomized controlled trial

ObjectivesTo determine the effects of a multicomponent physical exercise program on cognitive and affective functioning among nursing home residents and to clarify whether there are any changes in serum levels of brain-derived neurotrophic factor (BDNF) among participants. Study designThis was a single-blind randomized controlled trial in ten nursing homes in Gipuzkoa, Spain. The study included 112 men and women. Participants in the control group engaged in routine activities while those in the intervention group participated in a six-month individualized, progressive, multicomponent physical exercise program focused on strength, balance, and walking. Main outcome measuresCognitive and affective functions were assessed at baseline and at six months. Serum BDNF levels were assessed via ELISA. ResultsAfter six months, a group by time interaction in favor of the intervention group was observed on the Montreal Cognitive Assessment (MOCA), symbol search and De Jong-Gierveld Loneliness Scale (P < 0.05). The control group scored more poorly on the MOCA, WAIS-IV (coding and symbol search), verbal fluency, and semantic fluency tests after six months (P < 0.05) than they did at baseline. The intervention group showed poorer results on the coding test (P < 0.05). Loneliness perception was reduced in the intervention group (P < 0.05). No changes in serum BDNF were observed (group x time and within groups, P > 0.05). ConclusionA six-month individualized, progressive, multicomponent physical exercise intervention is effective at maintaining cognitive function and decreasing perceptions of loneliness among nursing home residents. Blood levels of BDNF were not affected by the intervention.

Ketamine-induced changes in plasma brain-derived neurotrophic factor (BDNF) levels are associated with the resting-state functional connectivity of the prefrontal cortex

Objectives Synaptic plasticity and brain-derived neurotrophic factor (BDNF) signalling are proposed to play key roles in antidepressant drug action. Ketamine, an N-methyl-D-aspartate receptor antagonist and putative antidepressant, may increase synaptic plasticity in prefrontal cortex through higher expression of BDNF. Furthermore, ketamine was shown to change resting-state functional connectivity (RSFC) of dorsomedial prefrontal cortex (dmPFC). Methods In a randomised, placebo-controlled study, we investigated acutely (100 min) and at 24 h following subanesthetic ketamine infusion which dmPFC seeded RSFC changes are most strongly associated with plasma BDNF level changes in 53 healthy participants (21 females, age: 24.4 ± 2.9 years) using 7 T-fMRI. Results We observed higher relative levels of BDNF 2 h and 24 h after ketamine compared to placebo. Whole-brain regression revealed that the change in BDNF after 24 h was associated with RSFC decreases from dmPFC to posterior cingulate cortex and ventromedial PFC at 24 h and exploratively also at the 100 min measurement point. Follow-up analyses revealed that RSFC reductions following ketamine were restricted to subjects showing increased BDNF levels at 24 h. Conclusions Our findings indicate BDNF level dynamics following ketamine are related to acute and 24 h RSFC changes. Particularly when BDNF increases are observed after ketamine infusion, a disconnection from dmPFC after 24 h is seen and may reflect synaptic plasticity effects.

Effects of attachment-based compassion therapy (ABCT) on brain-derived neurotrophic factor and low-grade inflammation among fibromyalgia patients: A randomized controlled trial

Fibromyalgia (FM) is a disabling syndrome characterized by chronic pain associated with fatigue. Its pathogenesis is unknown, but alterations in central sensitization, involving an imbalance of brain-derived neurotrophic factor (BDNF) and inflammatory biomarkers, appear to be implicated. The aim of this study was to evaluate the impact of attachment-based compassion therapy (ABCT) on levels of BDNF, the inflammatory markers TNF-α, IL-6, IL-10, and the C-reactive protein (CRP), analysing whether biomarkers play a mediating/moderating role in improvements in FM functional status. Thirty-four female patients with FM participated in a RCT and were assigned to ABCT or relaxation therapy. Blood extractions were conducted at baseline and post-intervention, with self-report assessments of functional status (FIQ) at baseline, post-intervention and 3-month follow-up. A pro-inflammatory composite was obtained by summing up IL-6, TNF-α and CRP normalized values. Non-parametric tests, analysis of variance and regression models were used to evaluate treatment and mediation/moderation. Compared to relaxation therapy, ABCT showed significant improvements in FIQ and decreases in BDNF, CRP, and pro-inflammatory composite. Changes in BDNF had a mediating role in FIQ. ABCT seems to reduce BDNF and appears to have anti-inflammatory effects in FM patients. Reductions in BDNF could be a mechanism of FM functional status improvement.Clinical Trial Registration:http://ClinicalTrials.gov, identifier NCT02454244. Date: May 27th, 2015.

Acute and regular exercise distinctly modulate serum, plasma and skeletal muscle BDNF in the elderly

Brain-derived neurotrophic factor (BDNF) participates in orchestrating the adaptive response to exercise. However, the importance of transient changes in circulating BDNF for eliciting whole-body and skeletal muscle exercise benefits in humans remains relatively unexplored. Here, we investigated effects of acute aerobic exercise and 3-month aerobic-strength training on serum, plasma and skeletal muscle BDNF in twenty-two sedentary older individuals (69.0 ± 8.0 yrs., 9 M/13F). BDNF response to acute exercise was additionally evaluated in young trained individuals (25.1 ± 2.1 yrs., 3 M/5F). Acute aerobic exercise transiently increased serum BDNF in sedentary (16%, p = .007) but not in trained elderly or young individuals. Resting serum or plasma BDNF was not regulated by exercise training in the elderly. However, subtle training-related changes of serum BDNF positively correlated with improvements in walking speed (R = 0.59, p = .005), muscle mass (R = 0.43, p = .04) and cognitive performance (R = 0.41, p = .05) and negatively with changes in body fat (R = -0.43, p = .04) and triglyceridemia (R = -0.53, p = .01). Individuals who increased muscle BDNF protein in response to 3-month training (responders) displayed stronger acute exercise-induced increase in serum BDNF than non-responders (p = .006). In addition, muscle BDNF protein content positively correlated with type II-to-type I muscle fiber ratio (R = 0.587, p = .008) and with the rate of post-exercise muscle ATP re-synthesis (R = 0.703, p = .005). Contrary to serum, acute aerobic exercise resulted in a decline of plasma BDNF 1 h post-exercise in both elderly-trained (−34%, p = .002) and young-trained individuals (−48%, p = .034). Acute circulating BDNF regulation by exercise was dependent on the level of physical fitness and correlated with training-induced improvements in metabolic and cognitive functions. Our observations provide an indirect evidence that distinct exercise-induced changes in serum and plasma BDNF as well as training-related increase in muscle BDNF protein, paralleled by improvements in muscle and whole-body clinical phenotypes, are involved in the coordinated adaptive response to exercise in humans.

Effects of macular xanthophyll supplementation on brain-derived neurotrophic factor, pro-inflammatory cytokines, and cognitive performance

PurposeOxidative and inflammatory processes play a major role in stress-induced neural atrophy. There is a wide body of literature linking oxidative and inflammatory stress with reductions in neurotrophic factors, stress resilience, and cognitive function. Based on their antioxidant and anti-inflammatory capacity, we investigated the effect of the dietary carotenoids lutein and zeaxanthin, along with the zeaxanthin isomer meso-zeaxanthin (collectively the “macular xanthophylls” [MXans]) on systemic brain-derived neurotrophic factor (BDNF) and anti-oxidant capacity (AOC), and the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. To investigate higher-order effects, we assessed cognitive performance. Methods59 young (18–25 yrs.), healthy subjects participated in a 6-month, double-blind, placebo-controlled trial to evaluate the effects of MXan supplementation on the aforementioned serum parameters and cognitive performance. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg/day total MXans; all measures were taken at baseline and 6 months. Blood was obtained via fasting blood draw, and MXan concentration in the retina (termed macular pigment optical density [MPOD]) was measured via customized heterochromatic flicker photometry. Serum BDNF and cytokines were assessed via ELISA. Serum antioxidant capacity (AOC) and serum MXan concentrations were quantified via colorimetric microplate assay, and high-performance liquid chromatography, respectively. Cognitive performance was measured via a computer-based assessment tool (CNS Vital Signs). ResultsBDNF, MPOD, serum MXans, and AOC all increased significantly versus placebo in both treatment groups over the 6-month study period (p < .05 for all). IL-1β decreased significantly versus placebo in both treatment groups (p = .0036 and p = .006, respectively). For cognitive measures, scores for composite memory, verbal memory, sustained attention, psychomotor speed, and processing speed all improved significantly in treatment groups (p < .05 for all) and remained unchanged in the placebo group. Several measures were found to be significantly associated in terms of relational changes over the course of the study. Notably, change in BDNF was related to change in IL-1β (r = −0.47; p < .001) and MPOD (r = 0.44; p = .0086). Additionally, changes in serum MXans were strongly related to AOC (r = 0.79 & 0.61 for lutein and zeaxanthin isomers respectively; p < .001). For cognitive scores, change in BDNF was correlated to change in composite memory (r = 0.32; p = .014) and verbal memory (r = 0.35; p = .007), whereas change in MPOD was correlated with change in both psychomotor speed (r = 0.38; p = .003), and processing speed (r = 0.35; p = .007). Change in serum lutein was found to be significantly correlated to change in verbal memory (r = 0.41; p < .001), composite memory (r = 0.31; p = .009), and sustained attention (r = 0.28; p = .036). Change in serum zeaxanthin isomers was significantly correlated with change in verbal memory (r = 0.33; p = .017). Lastly, change in AOC was significantly associated with verbal memory (r = 0.34; p = .021), composite memory (r = 0.29; p = .03), and sustained attention (r = 0.35; p = .016). No significant relational changes in any cognitive parameter were found for the placebo group. ConclusionsSix months of daily supplementation with at least 13 mg of MXans significantly reduces serum IL-1β, significantly increases serum MXans, BDNF, MPOD, and AOC, and improves several parameters of cognitive performance. Findings suggest that increased systemic antioxidant/anti-inflammatory capacity (and not necessarily deposition of the carotenoids in neural tissues), may explain many of the effects determined in this study. The significant relationship between change in BDNF and IL-1β over the course of the study suggests that regular consumption of MXans interrupts the inflammatory cascade that can lead to reduction of BDNF. Changes in MPOD and BDNF appear to account for enhancement in cognitive parameters that involve speed of processing and complex processing, respectively.ISRCTN Clinical Trial Registration: ISRCTN16156382.

Twelve weeks of resistance training does not influence peripheral levels of neurotrophic growth factors or homocysteine in healthy adults: a randomized-controlled trial.

There is growing evidence for a preventative effect of resistance training on cognitive decline through physiological mechanisms; yet, the effect of resistance training on resting growth factors and homocysteine levels is incompletely understood. This study aimed to investigate the effect of intense resistance training, for 12weeks, on changes in peripheral growth factors and homocysteine in late middle-aged adults. 45 healthy adults were enrolled into the single-site parallel groups' randomized-controlled trial conducted at the Department of Exercise Science, Strength and Conditioning Laboratory, Murdoch University. Participants were allocated to the following conditions: (1) high-load resistance training (n = 14), or (2) moderate-load resistance training (n = 15) twice per week for 12weeks; or (3) non-exercising control group (n = 16). Data were collected from September 2016 to December 2017. Fasted blood samples were collected at baseline and within 7 days of trial completion for the analysis of resting serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1, vascular endothelial growth factor, and plasma homocysteine levels. No differences in baseline to post-intervention change in serum growth factors or plasma homocysteine levels were observed between groups. A medium effect was calculated for BDNF change within the high-load condition alone (+ 12.9%, g = 0.54). High-load or moderate-load resistance training twice per week for 12weeks has no effect on peripheral growth factors or homocysteine in healthy late middle-aged adults. Australian New Zealand Clinical Trials Registry: ACTRN12616000690459.

The Role of Serum Levels of Insulin-Like Growth Factor-1 and Brain-Derived Neurotrophic Factor in Predicting Recovery in Stroke

Background: Despite the neurotrophins like brain-derived neurotrophic factor and insulin-like growth factor-1 are thought to have important role in neurorehabilitation, the factors that affect these biomarkers are not well known. Objectives: We aimed to investigate the effect of maximal aerobic exercise on serum neurotrophins levels in patients with chronic stroke and to investigate the factors that affect their resting and exercise-associated levels. Patients and Methods: Potential factors of resting and exercise-related serum neurotrophins levels were studied among 35 patients with chronic stroke. Resting brain derived neurotrophic factor, resting insulin-like growth factor, exercisedependent change brain derived neurotrophic factor, and exercise- dependent change in insulin-like growth factor were studied using demographic, disease burden, and cardiometabolic factors. Results: Brain-derived neurotrophic factor did not change after exercise (p = 0.38) while insulin-like growth factor decreased (p = 0.001). Higher resting brain-derived neurotrophic factor was determined by greater lower extremity impairment (p = 0.004, r2 = 0.23). The greater response of brain-derived neurotrophic factor to exercise was determined by higher fluid intelligence (p = 0.01, r2 = 0.18). Resting insulin-like growth factor-1 was not changed by all of the studied factors. Conclusion: Resting and percent change in brain-derived neurotrophic factor were associated with cognitive and physical recovery after chronic stroke. On the other hands, insulin-like growth factor-1 was not useful in chronic stroke. Interestingly, fluid intelligence was positively associated with exercise-related rise in brain-derived neurotrophic factor.