Evaluation of Possible Changes in Brain-Derived Neurotrophic Factor and Sleep Quality in Inactive Young Women with Vitamin D Deficiency after a Period of the High -Intensity Interval Running Training with Vitamin D Intake

Plasma brain-derived neurotrophic factor in women after bariatric surgery: a pilot study

Changes in plasma müllerian-inhibiting substance and brain-derived neurotrophic factor after chemotherapy in premenopausal women

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

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

Schizophrenia is a severe neuropsychiatric disorder ranking among the top ten global disability causes. In rodents, sub-chronic or chronic ketamine treatment is used for the induction of schizophrenia. Ketamine affects the function of brain-derived neurotrophic factor (BDNF), the most important neurotrophin involved in the pathophysiology of different neuropsychiatric disorders. The present systematic review aimed to investigate BDNF changes in rodent studies used ketamine-induced schizophrenia. PubMed electronic database was searched and 44 articles were found. After removal of unrelated articles, 17 articles were selected. The results showed a wide range of inconsistent changes in BDNF levels. We found that sub-chronic and chronic ketamine treatment in rats decreased BDNF or had no effect. Sub-chronic and chronic ketamine treatment in mice only decreased BDNF. However, increased BDNF was commonly observed following acute ketamine treatment. These results showed the possible role of species and the duration of treatment. Also, sex can also be involved in BDNF changes because one study showed inconsistent BDNF changes in male and female rats. In conclusion, we found that ketamine's effects may depend on factors such as duration of administration, sex, and species. Therefore, the wide range of BDNF changes may be related to high variability in methods. Because of this variability, there is currently no standardized method for using ketamine as a rodent model for schizophrenia. Further research is needed to establish a standardized pharmacological model of schizophrenia using ketamine treatment.

Obesity in youth increases the risk of type 2 diabetes (T2D), and both are risk factors for neurocognitive deficits. Exercise attenuates the risk of obesity and T2D while improving cognitive function. In adults, these benefits are associated with the actions of the brain-derived neurotrophic factor (BDNF), a protein critical in modulating neuroplasticity, glucose regulation, fat oxidation, and appetite regulation in adults. However, little research exists in youth. This study examined the associations between changes in diabetes risk factors and changes in BDNF levels after 6 months of exercise training in adolescents with obesity. The sample consisted of 202 postpubertal adolescents with obesity (70% females) aged 14–18 years who were randomized to 6 months of aerobic and/or resistance training or nonexercise control. All participants received a healthy eating plan designed to induce a 250/kcal deficit per day. Resting serum BDNF levels and diabetes risk factors, such as fasting glucose, insulin, homeostasis model assessment (HOMA-B—beta cell insulin secretory capacity) and (HOMA-IS—insulin sensitivity), and hemoglobin A1c (HbA1c), were measured after an overnight fast at baseline and 6 months. There were no significant intergroup differences on changes in BDNF or diabetes risk factors. In the exercise group, increases in BDNF were associated with reductions in fasting glucose (β = −6.57, SE = 3.37, p = 0.05) and increases in HOMA-B (β = 0.093, SE = 0.03, p = 0.004) after controlling for confounders. No associations were found between changes in diabetes risk factors and BDNF in controls. In conclusion, exercise-induced reductions in some diabetes risk factors were associated with increases in BDNF in adolescents with obesity, suggesting that exercise training may be an effective strategy to promote metabolic health and increases in BDNF, a protein favoring neuroplasticity. This trial is registered with ClinicalTrials.gov NCT00195858, September 12, 2005 (funded by the Canadian Institutes of Health Research).

The ability of synapses to undergo changes in structure and function in response to alterations of neuronal activity is an essential property of neural circuits. One way that this is achieved is through global changes in the molecular composition of the synapse; however, it is not clear how these changes are coupled to the dynamics of neuronal activity. Here we found that, in cultured rat cortical neurons, bidirectional changes of neuronal activity led to corresponding alterations in the expression of brain-derived neurotrophic factor (BDNF) and phosphorylation of its receptor tropomyosin-related kinase B (TrkB), as well as in the level of synaptic proteins. Exogenous BDNF reversed changes in synaptic proteins induced by chronic activity blockade, while inhibiting Trk kinase activity or depleting endogenous BDNF abolished the concentration changes induced by chronic activity elevation. Both tetrodotoxin and bicuculline had significant, but opposite, effects on synaptic protein ubiquitination in a time-dependent manner. Furthermore, exogenous BDNF was sufficient to increase ubiquitination of synaptic proteins, whereas scavenging endogenous BDNF or inhibiting Trk kinase activity prevented the ubiquitination of synaptic proteins induced by chronic elevation of neuronal activity. Inhibiting the proteasome or blocking protein polyubiquitination mimicked the effect of tetrodotoxin on the levels of synaptic proteins and canceled the effects of BDNF. Our study indicates that BDNF-TrkB signaling acts upstream of the ubiquitin proteasome system, linking neuronal activity to protein turnover at the synapse.

Decreased brain-derived neurotrophic factor (BDNF) has been demonstrated in animal models and patients with depression. However, little is known about changes in BDNF in post-stroke depression (PSD). This study investigated the changes in serum BDNF in patients with PSD, and evaluated whether serum concentrations of BDNF were associated with BDNF gene Val66Met polymorphism. PSD patients were diagnosed in accordance with DSM-IV criteria, and the severity of depression was evaluated with the Hamilton Rating Scale for depression. Serum BDNF was measured twice, first at 7 days after the onset of stroke and then at 3-6 months after stroke. Val66Met polymorphisms of the BDNF gene were determined using the polymerase chain reaction-restriction fragment length polymorphism method. BDNF concentrations and Val66Met polymorphisms were also measured in 30 healthly controls. A total of 93 patients admitted as a result of first time acute ischemic stroke were included. During the 6-month follow-up, 35 patients (37.6%) were diagnosed with PSD. Serum BDNF concentrations were decreased in PSD patients at 3-6 months after stroke (p < 0.05). The serum BDNF concentrations were not associated with BDNF gene Val66Met polymorphisms in either patients or healthy controls. Serum concentrations of BDNF decrease in PSD patients and BDNF may play an important role in the pathogenesis of PSD. However, Val66Met polymorphisms are not associated with serum concentrations of BDNF. The mechanism of decreased serum BDNF requires further study.

Frequency-dependent changes in synaptic plasticity and brain-derived neurotrophic factor (BDNF) expression in the CA1 to perirhinal cortex projection

Whole-body repeated hyperthermia increases irisin and brain-derived neurotrophic factor: A randomized controlled trial.

Brain-derived neurotrophic factor (BDNF) is consistently associated with acute mood episodes in bipolar disorder, but there is a lack of longitudinal data to support this hypothesis. In this 16-week open-label clinical trial, we tested the predictive role of BDNF Val66Met polymorphism on serum BDNF levels and the relationship of serum BDNF and clinical response in people with bipolar disorder during an acute illness episode. Sixty-four people with bipolar disorder who were medication-free at baseline and in an acute mood episode were recruited. They were matched with 64 healthy controls. Clinical evaluation, serum BDNF, and BDNF Val66Met polymorphism were determined at baseline, and change in serum BDNF was assessed in patients at weeks 2, 4, 8 and 16. There were no differences between patients and controls in serum BDNF or in frequencies of the BDNF Val66Met polymorphism genotype at baseline. The multivariable model showed that Met carriers had a significantly different change in BDNF levels compared with Val homozygotes. Not achieving a complete remission was also associated with lower prospectively assessed BDNF levels. This study provides the first longitudinal evidence that both the BDNF Val66Met polymorphism and remission status predict change in circulating BDNF levels.

Brain-derived neurotrophic factor (BDNF) is essential for neuroplasticity. Exercise can induce increases in forearm venous plasma and serum BDNF, often assumed to be indicative of release from the brain. We investigated the effects of exercise on circulating levels of mature BDNF (mBDNF) and its precursor proBDNF. Sixteen healthy, physically fit adults (20-40years old) cycled for 20min at 40, 60 and 80% of , separated by 30min of rest. BDNF was analysed in blood samples from the brachial artery, internal jugular vein, femoral vein and antecubital vein. Brain/skeletal muscle exchange of BDNF, calculated as arterial-venous differences in BDNF multiplied by blood flow in the middle cerebral artery/common femoral artery, was measured simultaneously with blood sampling. Exercise intensity-dependent increases were observed in blood platelet count, forearm venous serum mBDNF and plasma proBDNF, but not in forearm venous plasma mBDNF. Brain release (or uptake) was not detected for either plasma mBDNF, serum mBDNF or plasma proBDNF. However, muscle uptake of plasma mBDNF and release of plasma proBDNF were observed after high-intensity exercise. Our findings demonstrate that exercise-dependent increases in serum mBDNF are not derived from the brain or the exercised skeletal muscle. Rather, the source of the increase appears to be the increase in platelets that are enriched with mBDNF. Furthermore, in physically fit adults, BDNF is not released from the brain into the bloodstream, after exercise, regardless of exercise intensity. Finally, changes in plasma proBDNF after exercise appear to be dependent on exercised skeletal muscle rather than brain release. KEY POINTS: Previously shown exercise-induced increases in forearm venous brain-derived neurotrophic factor (BDNF) are often assumed to be indicative of release from the brain. We investigated whether exercise-induced changes in forearm venous mature BDNF (mBDNF) and precursor proBDNF are paralleled by concomitant changes in BDNF exchange over the brain and skeletal muscle. We observed exercise intensity-dependent increases in platelet count, forearm venous serum mBDNF and plasma proBDNF, but not in forearm venous plasma mBDNF. We found muscle uptake of plasma mBDNF and release of plasma proBDNF after high-intensity exercise but no exercise intensity-dependent brain exchange of either plasma mBDNF, serum mBDNF or plasma proBDNF. Our findings suggest that acute exercise-induced increases in circulating serum mBDNF may be solely a result of increased platelet count, probably due to splenic platelet release; and that exercised skeletal muscle, and not the brain, responds to high-intensity exercise by releasing plasma proBDNF.

Stress and trauma: BDNF control of dendritic-spine formation and regression

Regional-specific changes in rat brain BDNF in a model of methamphetamine abuse

Objective To explore serum levels of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF), and whether changes of BDNF and GDNF are correlated with sleep quality and cognitive function in patients with chronic insomnia disorder (CID). Methods Fifty-seven CID patients in the Department of Sleep Disorders, Chaohu Hospital of Anhui Medical University and 30 healthy controls were enrolled from May 2017 to July 2018. Pittsburgh Sleep Quality Index (PSQI) was used to assess the degree of insomnia severity (some CID patients were monitored by overnight polysomnography). Montreal Cognitive Assessment (MoCA) scale and Nine-Box Maze were used to assess general cognitive function and specific memory function, respectively. The serum levels of BDNF and GDNF were detected using ELISA. Results Compared to the controls, CID patients had significantly higher PSQI scores (CID patients: 14.0±2.2, healthy controls: 3.9±1.1; t=28.093, P<0.01), lower MoCA scores (CID patients: 24.5±3.6, healthy controls: 26.5±0.9; t=-2.985, P<0.01), more errors in object working memory (CID patients: 1.0 (0, 1.0), healthy controls: 0 (0, 0.3)), spatial working memory (CID patients: 3.0 (2.0, 4.0), healthy controls: 1.0 (1.0, 2.0)) and object recognition memory (CID patients: 0 (0, 0), healthy controls: 0 (0, 0); Z=-2.896、-5.007、-2.306, P<0.05), and lower serum BDNF (CID patients: (19.48±7.50) ng/ml, healthy controls: (46.49±13.33) ng/ml; t=-10.274, P<0.01) and GDNF (CID patients: (32.76±14.04) pg/ml, healthy controls: (59.63±20.30) pg/ml; t=-7.240, P<0.01). The partial correlation analysis showed that in the CID patients, the levels of BDNF and GDNF were correlated with PSQI scores negatively (r=-0.293, -0.320, P<0.05) and MoCA scores positively (r=0.331, 0.295, P<0.05). The BDNF level was also correlated with the duration of disease and the errors in the spatial working memory test negatively (r=-0.319, -0.393, P<0.05), and the GDNF level was correlated with the total sleep time detected with polysomnogram positively (r=0.520, P<0.05). Conclusion Serum BDNF and GDNF levels in CID patients were lower than those in healthy controls, and correlated with sleep quality and cognitive impairment. Key words: Insomnia; Neurotrophic factor; Cognitive function