Basal Brain-derived Neurotrophic Factor Levels Research Articles

Cognitive effects of transcranial direct current stimulation combined with working memory training in fibromyalgia: a randomized clinical trial

Cognitive dysfunction in fibromyalgia has been reported, especially memory. Anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) has been effective in enhancing this function. We tested the effects of eight sessions of tDCS and cognitive training on immediate and delayed memory, verbal fluency and working memory and its association with brain-derived neurotrophic factor (BDNF) levels. Forty females with fibromyalgia were randomized to receive eight sessions of active or sham tDCS. Anodal stimulation (2 mA) was applied over the DLPFC and online combined with a working memory training (WMT) for 20 minutes. Pre and post-treatment neurocognitive tests were administered. Data analysis on deltas considering years of education and BDNF as covariates, indicated active-tDCS + WMT significantly increased immediate memory indexed by Rey Auditory Verbal Learning Test score when compared to sham. This effect was dependent on basal BDNF levels. In addition, the model showed active stimulation increased orthographic and semantic verbal fluency scores (Controlled Oral Word Association Test) and short-term memory (Forward Digit Span). The combination of both techniques seemed to produce effects on specific cognitive functions related to short-term and long-term episodic memory and executive functions, which has clinical relevance for top-down treatment approaches in FM.

Visualizing BDNF Transcript Usage During Sound-Induced Memory Linked Plasticity.

Activity-dependent BDNF (brain-derived neurotrophic factor) expression is hypothesized to be a cue for the context-specificity of memory formation. So far, activity-dependent BDNF cannot be explicitly monitored independently of basal BDNF levels. We used the BLEV (BDNF-live-exon-visualization) reporter mouse to specifically detect activity-dependent usage of Bdnf exon-IV and -VI promoters through bi-cistronic co-expression of CFP and YFP, respectively. Enriching acoustic stimuli led to improved peripheral and central auditory brainstem responses, increased Schaffer collateral LTP, and enhanced performance in the Morris water maze. Within the brainstem, neuronal activity was increased and accompanied by a trend for higher expression levels of Bdnf exon-IV-CFP and exon-VI-YFP transcripts. In the hippocampus BDNF transcripts were clearly increased parallel to changes in parvalbumin expression and were localized to specific neurons and capillaries. Severe acoustic trauma, in contrast, elevated neither Bdnf transcript levels, nor auditory responses, parvalbumin or LTP. Together, this suggests that critical sensory input is essential for recruitment of activity-dependent auditory-specific BDNF expression that may shape network adaptation.

Interaction between different sports branches such as taekwondo, box, athletes and serum brain derived neurotrophic factor levels

This study aimed to compare serum brain-derived neurotrophic factor (BDNF) levels "which contributes in both neuron development/regeneration" between combat sport braches, which requires high attention and concentration and can lead micro and macro brain trauma, and athleticism, which requires durability in competition. The study design included 4 groups. Group 1 had sedentary participants, and group 2 athletes (middle and long runners) who exercised for two 2-hour daily training sessions 6 days a week. group 3 included boxers, and group 4 taekwondo fighters. We investigated changes in the blood BDNF levels of taekwondo fighters, boxers, and athletes before and after training and compared them among each other and with measurements of sedentary controls. All athletes had higher basal BDNF levels than sedentary participants. Boxers and taekwondo athletes had especially high basal BDNF levels. When we compared different sports branch each other Pre- and post- training BDNF values are ranked as follows: taekwondo > boxing > athletes > sedentary. In sport branches such as combat sports and athletes, serum BDNF levels have been demonstrated to be higher after training than before. In addition, serum BDNF levels were higher in taekwondo fighters and boxers than athletes. BDNF might have a role in the protection mechanism against brain damage or contributes in occurrence and maintenance of high attention and concentration especially among combat sports.

The impact of exercise training on basal BDNF in athletic adolescents.

[Purpose] The purpose of this study was to investigate the impact of exercise training on basal brain-derived neurotrophic factor in athletic adolescents. [Subjects and Methods] Twenty-two male adolescents participated in this study. The subjects were divided into a control group (n=9) and trained group (n=13). The trained group comprised table tennis athletes with more than 3 years of training who regularly exercised 18 hours per week. [Results] The results of this study show the trained group had significantly lower basal brain-derived neurotrophic factor levels than the control group. Further, platelet levels were significantly higher in the trained group than in the control group. However, no significant differences were observed between the groups in serum nerve growth factor level or physical characteristics (body weight, body mass index, fasting blood glucose). [Conclusion] This study showed that the basal brain-derived neurotrophic factor level of well-trained athletic adolescents was lower than that of the control group. Further research with a larger sample size is required to confirm the finding that lower basal brain-derived neurotrophic factor levels are associated with long-term habitual exercise in athletic adolescents.

CREB expression mediates amyloid β-induced basal BDNF downregulation

In Alzheimer's disease, accumulation of amyloid-β (Aβ) is associated with loss of brain-derived neurotrophic factor (BDNF), synapses, and memory. Previous work demonstrated that Aβ decreases activity-induced BDNF transcription by regulating cyclic adenosine monophosphate response element binding protein (CREB) phosphorylation. However, the specific mechanism by which Aβ reduces basal BDNF expression remains unclear. Differentiated, unstimulated human neuroblastoma (SH-SY5Y) cells treated with oligomeric Aβ exhibited significantly reduced CREB messenger RNA compared with controls. Phosphorylated and total CREB proteins were decreased in both the cytoplasm and nucleus of Aβ-treated cells. However, neither pCREB129 nor pCREB133 levels were altered relative to total CREB levels. The protein kinase A activator forskolin increased pCREB133 levels and prevented Aβ-induced basal BDNF loss when administered before Aβ but did not rescue BDNF expression when administered later. These data demonstrate a new mechanism for Aβ-induced BDNF downregulation: in the absence of cell stimulation, Aβ downregulates basal BDNF levels via Aβ-induced CREB transcriptional downregulation, not changes in CREB phosphorylation. Thus, Aβ reduces basal and activity-induced BDNF expression by different mechanisms.

Temporal regulation of peripheral BDNF levels during cocaine and morphine withdrawal: comparison with a natural reward.

Background:Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has long been studied in the field of addiction and its importance in regulating drug addiction–related behavior has been widely demonstrated. The aim of our study was to analyze the consequences of a repeated exposure to drugs of abuse or natural reward on plasma BDNF levels during withdrawal.Methods:Rats were chronically injected with morphine (subcutaneously, 5mg/kg) or cocaine (intraperitoneally, 20mg/kg) or fed with a butter biscuit (per os, 4g) once per day for 14 days. Blood collection was performed on the 1st (withdrawal day 1 or WD1) or on (WD14), either at the same time point rats had been exposed to drugs or natural reward or at a different time point (used to quantify basal brain-derived neurotrophic factor levels).Results:Cocaine treatment led to a rapid (WD1) and persistent (WD14) decrease of basal BDNF levels compared with saline-treated animals, whereas morphine induced an increase on WD14 without any alteration on WD1. On the contrary, the natural reward induced a significant increase of basal brain-derived neurotrophic factor levels only on WD1. The analysis of BDNF levels at the usual time point at which animals had been exposed showed that both drugs, but not the natural reward, increased BDNF levels compared with basal levels.Conclusion:Our data highlight that only drugs of abuse are able to persistently alter BDNF levels and to induce specific variations of this neurotrophic factor at the usual hour of injection.

The concentrations of serum, plasma and platelet BDNF are all increased by treadmill VO2max performance in healthy college men

The most current human-based studies in which brain-derived neurotrophic factor (BDNF) levels in the peripheral blood system are analyzed use it as an indicator that represents BDNF levels in the CNS. However, whether circulating BDNF (serum and plasma) is positively or inversely associated with cardiorespiratory fitness levels (VO2max) is still controversial, and no study has done to investigate exercise effects on the concentration of BDNF stored in circulating platelets which, in fact, store a large amount of circulating BDNF. Thus, the purpose of this study was to determine the relation between VO2max and all circulating BDNF levels (serum, plasma and platelets) in college male students (N=18; age, 19±1 years; height, 173.22±7.65cm; weight, 78.25±14.25kg; body fat percent, 13.82±5.68%). Dual X-ray energy absorptiometry whole body scan was used to measure their body composition. After the overnight fast, all participants were performed VO2max test, and their blood was collected at rest and immediately after the exercise. Our data resulted in significant increases in platelet counts and serum, plasma and platelet BDNF levels immediately after the exercise (p<0.01). VO2max had a significant negative correlation with serum BDNF, plasma BDNF and platelet BDNF at rest (p<0.05) but a significant positive correlation with serum, plasma BDNF, and platelet BDNF immediately after the exercise (p<0.01). However, our data show no correlation between VO2max and platelet count both at rest and immediately after the exercise. In conclusion, this is the first study showing that basal BDNF levels are inversely correlated with cardiorespiratory fitness levels but that the inverse correlations turn into positive correlations with all circulating BDNF levels immediately after the exercise. Moreover, it is the first time to provide evidence that platelet BDNF levels are also positively affected by the exercise. However, future studies will be needed to investigate what tissues provide BDNF into the circulating system and to elucidate the role of circulating BDNF.

The acute response of plasma brain-derived neurotrophic factor as a result of exercise in major depressive disorder

Brain-derived neurotrophic factor (BDNF) and other neurotrophins are believed to play an important role in affective disorders. In this study we investigated plasma-BDNF response during an incremental exercise test in 18 patients suffering from moderate major depressive disorder (MDD) and 18 controls. The patients were not treated with antidepressants or neuroleptics. Possible associations between plasma plasma-BDNF levels, dexamethasone suppression test cortisol levels and Montgomery-Åsberg Depression Rating Scale (MADRS) scores were also tested. No difference in basal BDNF levels between patients and controls was found. BDNF increased significantly during exercise in both male and female patients as well as in male controls, with no significant differences between the groups. BDNF levels declined after exercise, but after 60 min of rest BDNF levels showed tendencies to increase again in male patients. No correlation between BDNF and cortisol or MADRS scores was found. We conclude that unmedicated patients with moderate depression and normal activity of the hypothalamic-pituitary-adrenal axis do not have a disturbed peripheral BDNF release during exercise. The BDNF increase 60 min after interruption of exercise in male patients might indicate up-regulated BDNF synthesis, but this needs to be further investigated in future studies.

Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans

Acute and chronic exposure to cannabinoids has been associated with cognitive deficits, a higher risk for schizophrenia and other drug abuse. However, the precise mechanism underlying such effects is not known. Preclinical studies suggest that cannabinoids modulate brain-derived neurotrophic factor (BDNF). Accordingly, we hypothesized that Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the principal active component of cannabis, would alter BDNF levels in humans. Healthy control subjects (n = 14) and light users of cannabis (n = 9) received intravenous administration of (0.0286 mg/kg) Delta(9)-THC in a double-blind, fixed order, placebo-controlled, laboratory study. Serum sampled at baseline, after placebo administration, and after Delta(9)-THC administration was assayed for BDNF using ELISA. Delta(9)-THC increased serum BDNF levels in healthy controls but not light users of cannabis. Further, light users of cannabis had lower basal BDNF levels. Delta(9)-THC produced psychotomimetic effects, perceptual alterations, and "high" and spatial memory impairments. The effects of socially relevant doses of cannabinoids on BDNF suggest a possible mechanism underlying the consequences of exposure to cannabis. This may be of particular importance for the developing brain and also in disorders believed to involve altered neurodevelopment such as schizophrenia. Larger studies to investigate the effects of cannabinoids on BDNF and other neurotrophins are warranted.

Prenatal cocaine exposure decreases brain-derived neurotrophic factor proteins in the rat brain

The pregnant rats received daily sc injections of cocaine (30 mg/kg) or saline from the gestational day (GD) 7 to GD 20. At 1 week postnatal, all pups were killed and the hippocampus, cortex and striatum were dissected out. Levels of brain-derived neurotrophic factor (BDNF) under the basal condition and depolarization with high potassium (40 mM) were measured. The results showed that hippocampal BDNF levels under basal and depolarization conditions were all significantly lower in the pups prenatally exposed to cocaine than those exposed to saline. There were no significant differences in basal BDNF levels between the cocaine and saline groups in the cortex or striatum. However, the prenatally cocaine-treated pups showed significantly less BDNF release following high potassium depolarization than the saline-treated animals did in both these regions. The results support the suggestion that prenatal cocaine exposure decreases BDNF expression in the offspring.