Plasma Brain-derived Neurotrophic Factor Levels Research Articles

The effect of silymarin supplementation on cognitive impairment induced by diabetes in rats.

Background The objective of this investigation was to examine the impact of silymarin supplementation on locomotion, anxiety-related behavior, learning, and memory via several behavioral tests, such as open field, elevated plus maze, and Morris water maze tests in streptozotocin-induced diabetic rats. Methods The rats were divided into the control, diabetes, silymarin, and diabetes plus silymarin groups. On the 30th-35th days of the study, several behavioral tests were performed and blood and brain tissue samples were taken and brain-derived neurotrophic factor (BDNF) and histone deacetylase 3 (HDAC3) levels were analyzed. Results There was no significant difference in locomotor activity between the groups (p = 0.534). Spatial memory was lower (p = 0.000) but anxiety scores were higher (p = 0.005) in the diabetes group than in the control, silymarin, and diabetes plus silymarin groups. Plasma (p = 0.000) and brain tissue (p = 0.007) BDNF levels were lower in the diabetes group than in the control, silymarin, and diabetes plus silymarin groups; however, plasma (p = 0.432) and brain tissue (p = 0.321) HDAC3 levels did not significantly differ between the groups. Conclusions The findings obtained from this study suggest that silymarin supplementation could improve anxiety-related behavior, and learning and memory in diabetic rats by increasing the BDNF levels.

BDNF Val66Met genetic variation and its plasma level in patients with morbid obesity: A case-control study

Obesity is a major public health concern worldwide. Genetic, behavioral, and environmental factors contribute to the multifactorial etiology of obesity. Evidence suggests an association between human Brain-Derived Neurotrophic Factor (BDNF) Val66Met single nucleotide polymorphism (SNP) and obesity. Reduced plasma BDNF levels have also been reported in patients with eating disorders and obesity. We aimed to evaluate the BDNF Val66Met (rs6265) SNP and also plasma BDNF levels in morbidly obese patients compared with healthy normal controls in southern Iran. One hundred morbidly obese patients and one hundred eight healthy normal controls were enrolled. Blood-derived DNA samples were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed by DNA sequencing. Plasma BDNF levels were evaluated using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit for human BDNF. Data analysis was performed by SPSS software, version 18.0. Genotype distribution was not significantly different between obese patients and controls. However, plasma BDNF levels were significantly lower in obese patients compared with controls. Interestingly, a significant association was found between BDNF Val66Met SNP and plasma BDNF levels. No relationship was observed between BDNF Val66Met SNP and all assessed demographic and clinical characteristics of obese patients. It seems that plasma BDNF levels were associated with both obesity and BDNF Val66Met SNP. However, this association was not found between BDNF Val66Met SNP and obesity. Further studies with larger sample sizes are needed for more detailed assessment of this genetic variation as a potential biomarker for obesity.

Plasma brain-derived neurotrophic factor (BDNF) and sphingosine-1-phosphat (S1P) are NOT the main mediators of neuroprotection induced by resistance training in persons with multiple sclerosis—A randomized controlled trial

Resistance training (RT) has been shown to elicit neuroprotective effects in persons with multiple sclerosis (pwMS). Brain-derived neurotrophic factor (BDNF) and Sphingosine-1-phosphat (S1P) have been put forward as potent mediators of the neuroprotective effects induced by RT. However, while increases have been shown in acute and chronic circulating BDNF levels in pwMS following aerobic exercise alone or in combination with other exercise regimes, no studies have examined this in response to RT. As a novel ‘proof-of-concept’ approach, we therefore examined the effects of 24 weeks of RT on acute and chronic circulating BDNF and S1P levels in the same pwMS whom our group had previously observed RT-induced neuroprotective effects in (i.e. increased cortical thickness and preservation of whole brain volume). A total of n = 30 relapsing-remitting pwMS were randomized into a training group (TG: 24 weeks of progressive high intensity resistance training, 2 sessions per week; n = 16, age 44[40:51] years, EDSS score 3.0[2.0:3.5] (median[IQR]) or a control group (CG: 24 weeks of habitual lifestyle; n = 14, age 45[37:47] years, EDSS score 3.0[2.5:3.5]). Plasma levels of BDNF and S1P were assessed by ELISA kits before and after the 24-week intervention period. No within- or between group changes were observed in acute or chronic circulating levels of BDNF. A substantial proportion of the participants had S1P levels below the detection limit, yet no within- or between changes were observed in chronic S1P plasma levels in the remaining samples. Thus, the present findings do not support that circulating plasma BDNF or S1P levels are the main mediators of the neuroprotective effects previously reported in the same group of pwMS.

Higher BDNF plasma levels are associated with a normalization of memory dysfunctions during an antidepressant treatment.

One important symptom of patients with major depressive disorder (MDD) is memory dysfunction. However, little is known about the relationship between memory performance and depression severity, about the course of memory performance during antidepressant treatment as well as about the relationship between memory performance and brain-derived neurotrophic factor (BDNF). Memory function [learning and delayed recall) was assessed in 173 MDD patients (mean age 39.7 ± 11.3years] treated by a pre-defined treatment algorithm within the early medication change (EMC) study at baseline, days 28 and 56. Depression severity was assessed in weekly intervals, BDNF plasma levels were measured at baseline, days 14 and 56, BDNF exon IV and p11 methylation status at baseline. Linear mixed regression models revealed that the course of depression severity was not associated with the course of learning or delayed recall in the total group. 63 (36%) of the investigated patients showed memory deficits (percent range ≤ 16) at baseline. Of those, 26(41%) patients experienced a normalization of their memory deficits during treatment. Patients with a normalization of their delayed recall performance had significantly higher plasma BDNF levels (p = 0.040) from baseline to day 56 than patients with persistent deficits. Baseline BDNF exon IV promoter and p11 gene methylation status were not associated with memory performance. Our results corroborate a concomitant amelioration of learning and delayed recall dysfunctions with successful antidepressant therapy in a subgroup of patients and support a role of BDNF in the neural mechanisms underlying the normalization of memory dysfunctions in MDD. ClinicalTrials.gov number: NCT00974155; EudraCT: 2008-008280-96.

Effects of Cytochrome P450 2C19 Genetic Polymorphisms on Responses to Escitalopram and Levels of Brain-Derived Neurotrophic Factor in Patients With Panic Disorder.

The purpose of this study was to examine the relationships between ytochrome P450 family 2 subfamily C member 19 (CYP2C19) polymorphisms, brain-derived neurotrophic factor (BDNF) plasma levels, and treatment responses to escitalopram in Chinese patients with panic disorder (PD). Ninety patients with PD were administered the Panic Disorder Severity Scale-Chinese Version (PDSS-CV) and Hamilton Anxiety Scale (HAMA-14) from baseline to 8 weeks. Escitalopram treatment (10 mg/d) was administered for 8 consecutive weeks. Three CYP2C19 metabolizers, including extensive metabolizers, intermediate metabolizers, and poor metabolizers (PMs), and 5 CYP2C19 genotypes were detected by polymerase chain reaction-genotyping microarray analysis. Baseline plasma BDNF levels were tested using human BDNF enzyme-linked immunosorbent assay kits. Our findings showed no significant differences in demographic data, baseline PDSS-CV scores, or HAMA-14 scores between the 3 CYP2C19 metabolizer groups (P's > 0.05). Repeated-measures analysis showed a significant reduction in PDSS-CV (F = 221.49, df = 3, P < 0.001) and HAMA-14 (F = 260.47, df = 3, P < 0.001) scores over 8 weeks in PD patients. In addition, patients with PMs had a greater reduction in HAMA-14 scores (F = 2.14, P = 0.049) than did those with extensive metabolizers and intermediate metabolizers. Moreover, our findings showed that patients with *2/*2 genotypes had a greater reduction in PDSS-CV scores than did those with other genotypes (F = 2.14, df = 12, P = 0.015). Our study provides preliminary evidence of the effects of CYP2C19 PMs on treatment responses to escitalopram in Chinese PD patients, but no significant correlation between treatment responses and BDNF levels was found.

Acute and subsequent continuation electroconvulsive therapy elevates serum BDNF levels in patients with major depression

IntroductionThe induction of brain-derived neurotrophic factor (BDNF) release and subsequent restoration of neuroplastic homeostasis may underlie the effects of electroconvulsive therapy (ECT). ObjectivesWe aimed to assess serum and plasma BDNF levels during the course of acute ECT, as well as before and after subsequent continuation ECT, in patients with depression. MethodsWe included 24 patients with major depressive disorder (mean age ± SD: 54.5 ± 13.7; f/m: 17/7; baseline 17-item Hamilton Depression Rating Scale score of 26.79 ± 4.01). Serum and plasma BDNF (sBDNF, pBDNF) levels were assessed at nine time-points before, during, and after acute ECT series. Data were analysed using linear regression and linear mixed models, which were adjusted for multiple comparisons via Bonferroni correction. Five patients received continuation ECT subsequent to the acute ECT series. In these patients, BDNF levels were assessed before and after each two continuation ECT sessions using Wilcoxon signed-rank tests. ResultsRelative to baseline (mean ng/ml ±SD: 24.68 ± 14.40), sBDNF levels were significantly higher 1 day (33.04 ± 14.11, p = 0.013, corrected), 1 week (37.03 ± 10.29, p < 0.001, corrected), and 1 month (41.05 ± 10.67, p = 0.008, corrected) after the final ECT session, while pBDNF levels did not significantly differ (p > 0.1). Furthermore, our results indicated that sBDNF levels increased after each continuation ECT session. There was no significant association between sBDNF levels and clinical parameters or treatment response. ConclusionThe absence of an association between changes in sBDNF levels and depressive symptoms challenges the proposed concept of sBDNF/pBDNF as key markers of the effects of ECT.

Screening of brain-derived neurotrophic factor (BDNF) single nucleotide polymorphisms and plasma BDNF levels among Malaysian major depressive disorder patients.

BackgroundBrain-derived neurotrophic factor (BDNF) is a neurotrophin found in abundance in brain regions such as the hippocampus, cortex, cerebellum and basal forebrain. It has been associated with the risk of susceptibility to major depressive disorder (MDD). This study aimed to determine the association of three BDNF variants (rs6265, rs1048218 and rs1048220) with Malaysian MDD patients.MethodsThe correlation of these variants to the plasma BDNF level among Malaysian MDD patients was assessed. A total of 300 cases and 300 matched controls recruited from four public hospitals within the Klang Valley of Selangor State, Malaysia and matched for age, sex and ethnicity were screened for BDNF rs6265, rs1048218 and rs1048220 using high resolution melting (HRM).FindingsBDNF rs1048218 and BDNF rs1048220 were monomorphic and were excluded from further analysis. The distribution of the alleles and genotypes for BDNF rs6265 was in Hardy-Weinberg equilibrium for the controls (p = 0.13) but was in Hardy Weinberg disequilibrium for the cases (p = 0.011). Findings from this study indicated that having BDNF rs6265 in the Malaysian population increase the odds of developing MDD by 2.05 folds (95% CI = 1.48–3.65). Plasma from 206 cases and 206 controls were randomly selected to measure the BDNF level using enzyme-linked immunosorbent assay (ELISA). A significant decrease in the plasma BDNF level of the cases as compared to controls (p<0.0001) was observed. However, there was no evidence of the effect of the rs6265 genotypes on the BDNF level indicating a possible role of other factors in modulating the BDNF level that warrants further investigation.ConclusionThe study indicated that having the BDNF rs6265 allele (A) increase the risk of developing MDD in the Malaysian population suggesting a possible role of BDNF in the etiology of the disorder.

The Role of Enhanced Cognition to Counteract Detrimental Effects of Prolonged Bed Rest: Current Evidence and Perspectives.

Prolonged periods of physical inactivity or bed rest can lead to a significant decline of functional and cognitive functions. Different kinds of countermeasures (e.g., centrifugation, nutritional, and aerobic interventions) have been developed to attempt to mitigate negative effects related to bed rest confinement. The aim of this report is to provide an overview of the current evidence related to the effectiveness of computerized cognitive training (CCT) intervention during a period of complete physical inactivity in older adults. CCT, using a virtual maze navigation task, appears to be effective and has long-lasting benefits (up to 1.5 years after the study). Moreover, enhanced cognition (executive control) reduces decline in the ability to perform complex motor-cognitive dual-tasks after prolonged period of bed rest. It has been demonstrated that CCT administration in older adults also prevents bed rest stress-related physiological changes [these groups showed minimal changes in vascular function and an unchanged level of brain-derived neurotrophic factor (BDNF)] while control subjects showed decreased peripheral vascularization and increased plasma level of the neurotrophin BDNF during a 14-day bed rest. In addition, the effects of CCT are evident also from the brain electrocortical findings: CCT group revealed a decreased power in lower delta and theta bands while significant increases in the same EEG spectral bands power were found in control subjects. If we consider an increase of power in delta band as a marker of cortical aging, then the lack of shift of EEG power to lower band indicates a preventive role of CCT on the cortical level during physiological deconditioning induced by 2-week bed rest immobilization. However, replication on a larger sample is required to confirm the observed findings. Applications derived from these findings could be appropriate for implementation of hospital treatment for bed ridden patients as well as for fall prevention programs.

Brain-derived neurotrophic factor is associated with cognitive impairments in first-episode and chronic schizophrenia

Brain-derived neurotrophic factor (BDNF) may be related to the pathophysiology of schizophrenia. This study aims to examine the relation between plasma BDNF levels and the cognition of patients with schizophrenia. We recruited 31 patients with chronic schizophrenia, 34 first-episode patients, and 35 healthy control subjects. We examined the MATRICS Consensus Cognitive Battery (MCCB) and the plasma BDNF levels in all groups. The schizophrenic symptoms were assessed using the positive and negative syndrome scale. The BDNF levels of schizophrenic patients were remarkably lower than those of the controls. The cognitive MCCB global composite scores and part index scores of schizophrenic patients were remarkably lower than those of the controls. Moreover, remarkable correlations were observed between BDNF levels and partial cognitive dimensions, such as visual learning, memory, and processing speed. Therefore, BDNF may be involved in the pathophysiology and cognitive impairment of schizophrenia.

BDNF+/- rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders.

Major depressive disorder (MDD) is a leading contributor to the global burden of disease. However, the causal relationship of risk factors, such as genetic predisposition or experience of augmented stress, remain unknown. Numerous studies in humans and rodents have implicated brain-derived neurotrophic factor (BDNF) in MDD pathology, as a genetic risk factor and a factor regulated by stress. Until now, the majority of preclinical studies have employed genetically modified mice as their model of choice. However, mice display a limited behavioural repertoire and lack expression of circulating BDNF, which is present in rats and humans. Therefore, heterozygous BDNF (BDNF+/- ) rats were tested for affective behaviours and accompanying expression of key genes associated with affective disorders in the brain. We found that BDNF+/- rats, which have reduced BDNF levels in brain and plasma, displayed symptoms of anhedonia, a core symptom of MDD, and anxiety-like behaviour, but no behavioural despair or cognitive impairments. This was accompanied by changes in the expression of genes that are implicated in modulation of the stress response and affective disorders. Hence, glucocorticoid receptor, neuregulin 1 and disrupted-in-schizophrenia 1 gene expression were upregulated in the prefrontal cortex of BDFN+/- rats, whereas FK506 binding protein 5 levels were decreased in the hippocampus. We conclude that a reduction in BDNF levels alters expression of genes associated with affective disorders, which may contribute to the development of depressive-like symptoms.

Association between reduced brain-derived neurotrophic factor concentration & coronary heart disease.

Background & objectives:Brain-derived neurotrophic factor (BDNF) facilitates neuronal survival, differentiation and synaptic connectivity and affects neurotransmission throughout the brain. However, it has also a modulatory role in energy homeostasis, obesity and cardiovascular function. Obesity, high body mass index (BMI) and dyslipidaemia, among other factors, contribute to coronary heart disease (CHD) development. The exact role of BDNF in development of CHD is not well defined. This study was aimed to evaluate if plasma BDNF concentration was associated with CHD in ethnically homogeneous groups of patients and to correlate plasma BDNF levels with known risk factors for CHD.Methods:Plasma BDNF concentration, BDNF Val66Met polymorphism and other biological and anthropological risk factors for CHD were determined in 208 patients with CHD and 156 healthy controls.Results:Plasma BDNF concentration was significantly (P<0.01) reduced in patients with CHD compared to controls, and it was not influenced by gender, age, smoking or BDNF Val66Met polymorphism. It was considerably correlated with cholesterol (P=0.004), low-density lipoprotein (P=0.006), and diastolic blood pressure (P=0.018) in patients with CHD and with platelet number (P=0.003) in healthy controls.Interpretation & conclusions:The results revealed lower plasma BDNF concentration in patients with CHD, suggesting that decreased plasma BDNF concentration might be associated with CHD pathogenesis. Longitudinal studies with a large sample need to be conducted to confirm these findings.

The impact of plasma brain-derived neurotrophic factor concentration and weight gain after kidney transplantation.

Obesity and its related complications continue to be significant challenges for kidney transplant recipients. In previous studies, researchers have reported that brain-derived neurotrophic factor (BDNF) is closely associated with metabolic imbalance and obesity, but the role of BDNF in weight gain after kidney transplant has not been elucidated. The purpose of this pilot study was to explore the relationship between plasma BDNF levels and weight change. We examined associations between plasma BDNF levels measured at transplantation and 12 months later and measures of weight change during these 12 months in a sample of 55 kidney recipients (mean age of 48 years, 60% male, 56% African American). Of the 55 recipients, 49 had BDNF levels measured at baseline, 33 had BDNF levels measured at 12 months, and 27 had BDNF levels measured at both time points. We found that plasma BDNF levels at baseline (n = 49), but not at 12 months (n = 33), were significantly and positively correlated with the body mass index change (p = 0.037) and percentage weight change (p = 0.036). In addition, average plasma BDNF value at 12 months (307 ± 254 pg/ml) was significantly lower than at baseline (452 ± 345 pg/ml) in the 27 recipients with BDNF levels measured at both time points. Findings from this pilot work suggest that BDNF might serve as a regulator of weight change for kidney transplant related obesity.

Genetic Variants of the Brain-Derived Neurotrophic Factor and Metabolic Indices in Veterans With Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a trauma and stressor related disorder that may develop after exposure to an event that involved the actual or possible threat of death, violence or serious injury. Its molecular underpinning is still not clear. Brain-derived neurotrophic factor (BDNF) modulates neuronal processes such as the response to stress, but also weight control, energy and glucose homeostasis. Plasma BDNF levels and a functional BDNF Val66Met (rs6265) polymorphism were reported to be associated with PTSD, as well as with increased body mass index (BMI) and dyslipidaemia in healthy subjects and patients with cardio-metabolic diseases, but these results are controversial. The other frequently studied BDNF polymorphism, C270T (rs56164415), has been associated with the development of different neuropsychiatric symptoms/disorders. As far as we are aware, there are no data on the association of BDNF Val66Met and C270T polymorphisms with metabolic indices in PTSD. Due to high rates of obesity and dyslipidaemia in PTSD, the aim of this study was to elucidate the association of BDNF Val66Met and C270T polymorphisms with BMI and lipid levels in veterans with PTSD. We hypothesized that BDNF variants contribute to susceptibility to metabolic disturbances in PTSD. The study included 333 Caucasian males with combat related PTSD, diagnosed according to DSM-5 criteria. Genotyping of the BDNF Val66Met and C270T polymorphisms was performed using the real-time PCR method. Results were analyzed using hierarchical multiple linear regression and the Mann–Whitney test, with p-value corrected to 0.005. The results showed that BDNF Val66Met and BDNF C270T polymorphisms were not significantly associated with BMI, total cholesterol, LDL-cholesterol, HDL-cholesterol or triglycerides. Although the BDNF C270T polymorphism was nominally associated only with HDL-cholesterol in veterans with PTSD, this significance disappeared after controlling for the effect of age. Namely, slightly higher plasma HDL values in T allele carriers, compared to CC homozygotes, were associated with differences in age. Our results, controlled for the critical covariates, revealed that BDNF Val66Met and C270T were not significantly associated with metabolic indices in veterans with PTSD and that these genetic variants do not contribute to susceptibility to metabolic disturbances in PTSD.

Exercise training increases cardiac, hepatic and circulating levels of brain-derived neurotrophic factor and irisin in young and aged rats.

Background The objective of study was to examine the impacts of exercise training on cardiac, hepatic and plasma brain-derived neurotrophic factor (BDNF) and irisin levels in young and aged rats. Materials and methods Four-month-old (young) and 20-month-old (aged) female rats performed exercise training consisting of voluntary wheel running for 12 weeks. BDNF and irisin levels were analyzed in the heart, liver and plasma samples by using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Results Cardiac, hepatic and plasma BDNF levels were lower in the aged sedentary rats, than in the young exercised and aged exercised rats (p < 0.05). Heart, liver and plasma irisin concentrations were lower in the aged sedentary group than in the young sedentary, young exercised and aged exercised groups (p < 0.05) and regular exercise increased irisin levels in all the analyzed tissues when compared to the sedentary counterparts (p < 0.05). Conclusions The current results show that regular exercise improves aging-induced decrease in the cardiac, hepatic and plasma BNDF and irisin levels.

Dynamic association of plasma brain-derived neurotrophic factor, neuron-specific enolase, and S100β with delirium in critically ill patients

Objective To determine the association between plasma concentrations of brain derived neurotrophic factor (BDNF), neuron-specific enolase (NSE), and S100β, and the occurrence of delirium in critically ill patients. Methods Totally 65 patients in Intensive Care Unit (ICU) of Wuxi People’s Hospital of Nanjing Medical University between June 2015 and February 2016 were included in the present study. Delirium diagnosis was used by confusion assessment method for the ICU (CAM-ICU). Plasma BDNF, NSE, and S100β concentrations were determined on day 1(T1), 3(T3), and 10(T10) after ICU admission. The day of ICU admission was defined as T0. Results Compared with the plasma BDNF level on T1 (0.23±0.22) μg/L, the plasma BDNF level on T3 (0.59±0.34) μg/L and T10 (0.24±0.21) μg/L were higher, especially for that on T3 with a significant difference (F=21.58, P=0.018). Plasma NSE level on T3 (1.68±0.25) μg/L was significantly higher than that on T1 (1.22±0.32) μg/L (F=10.24, P=0.042). Compared with those without delirium, the delirious patients had lower BDNF, higher NSE and S100β on T1, T3 and T10, of which the difference of BDNF [T1: (0.23±0.22) μg/L vs. (1.02±0.24) μg/L, F=116.25, P<0.01; T3: (0.59±0.34) μg/L vs. (1.55±0.36) μg/L, F=82.39, P<0.01; T10: (0.24±0.21) μg/L vs. (1.09±0.55) μg/L, F=50.93, P=0.003, and NSE (T1: (1.22±0.32) μg/L vs. (0.47±0.23) μg/L, F=94.30, P<0.01; T3:(1.68±0.25) μg/L vs. (0.79±0.28) μg/L, F=78.63, P=0.017; T10: (0.98±0.37) μg/L vs. (0.51±0.22) μg/L, F=70.95, P=0.026) reached significant differences. Conclusions Plasma BDNF and NSE are closely related to the occurrence of delirium in critically ill patients, especially for BDNF. Clinical monitoring of plasma levels of BDNF can help to predict the outcome of brain function in critically ill patients. Key words: Brain derived neurotrophic factor; Neuron-specific enolase; Plasma; Critically ill patients; Delirium; Dynamic alteration; Brain function; Outcome

Daily Intermittent Normobaric Hypoxia Over 2 Weeks Reduces BDNF Plasma Levels in Young Adults - A Randomized Controlled Feasibility Study.

Background: The results from animal and human research indicate that acute intermittent hypoxia can enhance brain-derived neurotrophic factor (BDNF) plasma levels and gene expression. As BDNF is known to promote the differentiation of new neurons and the formation of synapses, it has been proposed to mediate adult neuroplasticity. Thus, the present study aimed to analyze the long-term effects of daily intermittent exposure to normobaric hypoxia (simulating high altitude exposure at approximately 4000–5000 m) over 2 weeks on BDNF levels in young adults.Methods: Twenty-eight young adults (age: 19–33 years) were randomized into a hypoxic intervention group (N = 14) or the control group (N = 14). Participants in the intervention group breathed intermittent normobaric hypoxic air at resting conditions (5 min intervals, 80–85% SpO2 measured via a finger pulse oximeter, 12 sessions for 60 min/day for 2 weeks) via a hypoxic generator. BDNF plasma and serum levels were determined at baseline and at 2 weeks after intervention using sandwich ELISAs.Results: After 2 weeks of daily intermittent hypoxic treatment (IHT), we found a significant group x time interaction effect for BDNF plasma levels based on a significant decrease in BDNF levels in the hypoxia group.Conclusion: Our results demonstrate that daily intermittent administration of hypoxic air has a significant effect on BDNF regulation in healthy young adults. Contrary to other results reporting an increase in BDNF levels under hypoxic conditions, the present data suggest that hypoxic treatment using intensive IHT can reduce BDNF plasma levels for at least 2 weeks. This finding indicates that the daily application of hypoxic air is too frequent for the aimed physiological response, namely, an increase in BDNF levels.

Increase in Blood Levels of Growth Factors Involved in the Neuroplasticity Process by Using an Extremely Low Frequency Electromagnetic Field in Post-stroke Patients.

Background: Neuroplasticity ensures the improvement of functional status in patients after stroke. The aim of this study was to evaluate the effect of extremely low-frequency electromagnetic field therapy (ELF-EMF) on brain plasticity in the rehabilitation of patients after stroke.Methods: Forty-eight patients were divided into two groups underwent the same rehabilitation program, but in the study group, the patients additionally were exposed to a standard series of 10 ELF-EMF treatments. To determine the level of neuroplasticity, we measured the plasma level of the brain-derived neurotrophic factor (BDNF), the vascular-endothelial growth factor, as well as BDNF mRNA expression. Additionally, we determined the molecule levels for hepatocyte growth factor, stem cell factor, stromal cell-derived factor 1α, nerve growth factor β, and leukemia inhibitory factor, using 5plex cytokine panel in plasma. After 4 weeks, during which patients had undergone neurorehabilitation and neurological examinations, we assessed functional recovery using the Barthel Index, Mini-Mental State Examination (MMSE), Geriatric Depression Scale, National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS).Results: We observed that ELF-EMF significantly increased growth factors and cytokine levels involved in neuroplasticity, as well as promoted an enhancement of functional recovery in post-stroke patients. Additionally, we presented evidence that these effects could be related to the increase of gene expression on the mRNA level. Moreover, a change of BDNF plasma level was positively correlated with the Barthel Index, MMSE, and negatively correlated with GDS.Conclusion: Extremely low-frequency electromagnetic field therapy improves the effectiveness of rehabilitation of post-stroke patients by improving neuroplasticity processes.

Alcohol-induced cognitive deficits are associated with decreased circulating levels of the neurotrophin BDNF in humans and rats.

Chronic alcohol consumption is associated with neurocognitive and memory deficits, dramatically affecting plasticity and connectivity, with maximal expression as dementia. Neurotrophic factors may contribute to alcohol-related cognitive decline. For further investigation, a cross-sectional study was performed to evaluate the association of cognitive impairment, by using frontal assessment battery, and memory loss, using memory failures everyday, with the circulating levels of the neurotrophin brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in abstinent subjects with alcohol use disorders (AUDs, N=58, average of 17.9years of problematic use and 4.3months of abstinence) compared with healthy control subjects (N=22). This association was also explored in a pre-clinical model of adolescent rats chronically exposed to alcohol up to adulthood (~77days old) in a three-bottle free-choice (5-10-20 percent), repeated abstinence and relapse paradigm. AUD subjects had low educational level and cognitive impairment associated with teenage consumption and lower circulating levels of BDNF and NT-3. Only BDNF concentration showed a positive correlation with frontal assessment battery in AUD patients. In the ethanol-exposed rats, the plasma levels of BDNF and NT-3 were also decreased, and a negative correlation between hippocampal Bdnf mRNA levels and recognition memory was found. The ethanol-exposed rat hippocampus showed a decrease in the mRNA levels of neurotrophic (Bdnf and Ntf-3) and neurogenic (Mki67, Sox2, Dcx, Ncam1 and Calb1) factors, associated to a deactivation of the neurogenic regulator mitogen-activated protein kinase extracellular signal-regulated kinase. Results suggest a relevant role of BDNF/extracellular signal-regulated kinase 2 signaling in alcohol-induced cognitive impairment and suggest that early alcohol exposure-derived effects on cognition are associated with neurotrophin signaling deficits.

Pulmonary rehabilitation and BDNF levels in patients with chronic obstructive pulmonary disease: A pilot study

BackgroundCOPD physiopathology involves multiple pathways and evidence indicates that brain-derived neurotrophic factor (BDNF) is an important biomarker associated with parameters of COPD severity. This study aimed to analyze the time course of the effects of a pulmonary rehabilitation program (PRP) on BDNF levels and on functional status in COPD patients. MethodsPatients were enrolled in a 24-session PRP. Exercise capacity, dyspnea, health-related quality of life, and the BODE index were assessed at baseline and after the PRP. BDNF plasma levels were measured at baseline (immediately before the 1st session), after the 1st session, and before and after the 24th session. ResultsSixteen patients were included. A reduction in BDNF levels was observed after the 1st session and an increase was observed between the end of the 1st session and the beginning of the 24th session. The PRP promoted an improvement in exercise capacity and health-related quality of life and a reduction in dyspnea and the BODE index. ConclusionExercise acutely reduced BDNF levels, an effect that was nullified by the overall intervention.

Association Between Objectively Measured Physical Activity and Plasma BDNF in Adolescents: DADOS Study

Brain-derived neurotrophic factor (BDNF) is suggested to play a key role in moderating the benefits of physical activity (PA) on cognition. Previous research found that PA may have an impact on peripheral BDNF expression. The aim of our study was to analyze the association between objectively measured PA with circulating BDNF in a group of active adolescents. Two hundred thirty-four adolescents (132 boys) aged 13.9 ± 0.3years old from the DADOS study were included in this cross-sectional analysis. PA was assessed by GENEActiv triaxial accelerometer. Participants wore the accelerometer on their non-dominant wrist for 6 consecutive 24-h days, including weekends. PA was expressed as the average (min/day) of light, moderate, and vigorous PA. Fasting plasma BDNF concentrations at rest were measured using an enzyme-linked immunosorbent assay. Partial correlations and linear regression analyses were performed with a significance level established at p < 0.05. No correlations were found between BDNF and PA variables. Plasma levels of BDNF at rest were not significantly associated with daily PA in either boys or girls (p > 0.05). Based on previous research and our own data, the association between daily PA and baseline levels of BDNF remains inconclusive. Further research is needed to shed light on the relationship between regular PA and BDNF in adolescents.