Serum Brain-derived Neurotropic Factor Research Articles

Abstract 17674: Serum Brain-Derived Neurotropic Factor Levels Predict the Recurrences of Atrial Fibrillation Following Catheter Ablation

Background: Brain-derived neurotropic factor (BDNF) is a growth factor with roles within the nervous system and cardiovascular system. It has been reported that serum BDNF is decreased in diseases related to persistent stress, such as chronic inflammation. Atrial fibrillation (AF) is also considered to be one of the diseases related to chronic inflammation, although the relationship between serum BDNF and AF remains unclear. Methods: This prospective study included 68 consecutive patients (44 men; 69 [58-69] years) who underwent first session of paroxysmal AF ablation. Before and 3 months after the ablation, blood samples were obtained to measure the several biomarkers that are known to be related to AF in addition to serum BDNF. AF recurrence was defined as the appearance of AF after 3 month blanking period following the ablation. Results: The serum BDNF levels before ablation were significantly increased after AF ablation (3.5 [1.6-16.6] ng/ml vs. 22.1 [16.2-27.4] ng/ml, p<0.001). During follow-up period of 10±2 months, AF recurrence occurred in 5 (7%) patients. The serum BDNF at 3 months post-ablation were significantly lower in patients with recurrent AF than in those without (19.6 [13.8-20.8] ng/ml vs. 22.0 [17.5-27.1] ng/ml, p=0.019). Furthermore, the serum BDNF at 3 months post-ablation was an independent predictor of AF recurrence (odds ratio 0.912, 95% confidence interval 0.835-0.996, p=0.040). According to the ROC curve analysis, the serum BDNF at 3 months post-ablation <22.0 ng/ml was associated with AF recurrence with 100% sensitivity and 54% specificity (area under the curve=0.817, p=0.019). Kaplan-Meier survival curve showed that the recurrence rate of AF was higher in the group L (the serum BDNF at 3 months post-ablation <22.0 ng/ml) than the group H at 3 months post-ablation >22.0 ng/ml) (p = 0.02) [figure 1]. Conclusions: Lower serum BDNF levels at 3 months after blanking period following the AF ablation might be a predictor of AF recurrence.

Gut microbiota indole-3-propionic acid mediates neuroprotective effect of probiotic consumption in healthy elderly: A randomized, double-blind, placebo-controlled, multicenter trial and in vitro study

The beneficial effects of probiotic consumption on age-related decline in cerebral function have been previously reported in the literature; however, the mechanistic link between gut and brain interactions has not yet been fully elucidated. Therefore, this study aimed to identify the role of gut microbiota-derived metabolites in gut-brain interactions via blood metabolomic profiling analysis in clinical trials and invitro mechanistic studies. A randomized, double-blind, placebo-controlled, multicenter clinical trial was conducted in 63 healthy elderly individuals (≥65 years of age). Participants were administered either placebo (placebo group, N=31) or probiotic capsules (Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI; probiotics group, N=32) for 12 weeks. Global and targeted metabolomic profiling analyses of their blood samples were then performed using 1H nuclear magnetic resonance and liquid chromatography-mass spectrometry methods, both at baseline and at the end of the trial. Gut microbial analysis was conducted using the 16S ribosomal ribonucleic acid gene sequencing method. Subsequently, microglial BV2 cells were treated invitro with indole-3-propionic acid (IPA) following lipopolysaccharide stimulation, and neuronal SH-SY5Y cells were treated with conditioned media from the BV2 cells. Finally, the levels of pro-inflammatory cytokines in BV2 cells and neurotrophins in SH-SY5Y cells were quantified using a real-time polymerase chain reaction or enzyme-linked immunosorbent assay. The metabolomic profiling analyses showed that probiotic consumption significantly altered the levels of metabolites involved in tryptophan metabolism (P<0.01). Among these metabolites, gut microbiota-produced IPA had a 1.91-fold increase in the probiotics group (P<0.05) and showed a significant relation to gut bacterial profiles (P<0.01). Elevated IPA levels were also positively associated with the level of serum brain-derived neurotropic factor (BDNF) in the probiotics group (r=0.28, P<0.05), showing an inverse trend compared to the placebo group. In addition, invitro treatment with IPA (5μM) significantly reduced the concentration of proinflammatory TNF-α in activated microglia (P<0.05), and neuronal cells cultured with conditioned media from IPA-treated microglia showed a significant increase in BDNF and nerve growth factor production (P<0.05). These results show that gut microbiota-produced IPA plays a role in protecting the microglia from inflammation, thus promoting neuronal function. Therefore, this suggests that IPA is a significant mediator linking the interaction between the gut and the brain in the elderly with probiotic supplementation.

Effects of Different Intensity Aerobic Exercise on Circulating Levels of Neurotrophic Factor in Healthy and Hyperlipidemic Adults in A Local Population

Objective: The present study is to compare the pre and post serum BDNF levels in healthy and hyperlipidemic population at baseline and post 12 weeks of exercise and to correlate the pre and post serum BDNF levels in healthy and hyperlipidemic population at baseline and post 12 weeks of exercise.&#x0D; Study Design: Two arm follow up non-blinded randomized controlled trial (RCT).&#x0D; Place and Duration of Study: Physiology department, Basic Medical Science Institute (BMSI), Jinnah Post-Graduate Medical Center (JPMC), Karachi&#x0D; Methodology: A total 258 participants of any age were divided into two groups: 129 participants in one of the two groups, Group-1 adult hyperlipidemic group and Group-2 healthy adults group. Both groups were additional divided into 3 subgroups with different exercise intensity i.e. light, moderate and high intensity exercise. To evaluate the health status of participants, graded exercise test by using Bruce protocol and the HRmax was performed and given a specific exercise program for 12 weeks. The test was a conducted as per Bruce protocol (Smith 2013), using a treadmill with heart rate monitoring and ECG monitor. Blood sample had been taken for the analysis of total cholesterol and serum levels of BDNF.&#x0D; Results: Mean levels of brain derived neurotropic factor (BDNF) of healthy and hyperlipidemic participants in all three different intensity exercise group (A, B, and C) at baseline and three follow-ups shown no statistically significant difference between LIEG on BDNF level from baseline (day zero) till three consecutive follow ups (p&gt;0.05). While, in moderate (p&lt;0.05) and high intensity participants (p&lt;0.01) demonstrated an increase in BDNF levels at 90th day when compared from baseline i.e. day zero. Prominently, no significant difference observed at baseline (p&gt;0.05), however a significant difference was found at day 30, 60 and 90 (p &lt;0.05, 20.01, &lt;0.001) respectively.&#x0D; Conclusion: In light of our findings we conclude that 12 weeks of moderate to high intensity exercise progress cognitive function, serum BDNF levels, and improved lipid profile parameters, while low intensity exercise showed no significant mean difference for healthy participants.

Assessment of Cortisol, Brain-Derived Neurotropic factor, C - reactive protein, Interleukin-6 levels and cognitive decline after trauma exposure

Background: Studies have found that multiple neurobiological mechanisms are underlying the cause of Posttraumatic stress that influence the nervous and immune system leading to neurodegenerative and psychiatric comorbidities. The present study aims to assess and evaluate the serum Cortisol, C - reactive protein (CRP), Interleukin-6 (IL-6), Brain-Derived Neurotropic Factor (BDNF) levels and cognitive decline among subjects with trauma exposure and to determine the relationship between the above-specified stress biomarkers.&#x0D; Methodology: Two groups with trauma exposure (including natural disaster, any accident, physical and/or verbal violence, or any stressful condition) in the last twelve months were recruited. Groups were majorly divided based on TSC-40 (Trauma Symptom Checklist - 40) scores. Subjects with a TSC score &gt; 40 were kept in the traumatized group, while those with TSC score &lt; 40 were included in the control group. A total of 188 subjects above the age of 18 were recruited following inclusion criteria, cognition was measured using the Six-Item Cognitive Impairment Test (6-CIT), and serum samples were obtained for cortisol, CRP, BDNF, and IL-6 levels.&#x0D; Results: There was a significant difference in the serum BDNF (P&lt;0.001) level among the traumatized subjects, i.e. 15.68 ± 3.55 ng/dl as compared to controls 26.65 ± 2.47 ng/dl; no significant difference was found in CRP levels (ns) in both groups with a slight increase among the traumatized subjects as compared to the controls, i.e. 4.29 ± 1.50 mg/dl vs. 3.42 ± 1.11 mg/dl. As indicated by the 6-CIT score, the cognitive decline was more pronounced among the traumatized subjects, i.e. 8.54 ± 2.13 compared to the control group 5.0 ± 1.81, with a significant positive difference (p&lt;0.001).&#x0D; Conclusion: The finding suggests that traumatic stress is associated with Cognitive decline, BDNF and cortisol, whereas a non-significant association was found with IL-6 and CRP levels.

Association of blood lead levels with neurobehavior and BDNF expression in school going children

BackgroundChildhood Lead (Pb) toxicity has been an ongoing concern for decades; however, its underlying pathogenesis remains unclear. Although its prevalence has come down in developed countries (USA, Europe); it is relatively high in low to middle-income countries of South-East Asia. The current study aimed to evaluate the association of blood lead levels (BLLs) with neurobehavioral alterations and changes in Brain-Derived Neurotropic Factor (BDNF) expression in Indian school children. MethodologySchool going children in age group of 9–15 years (N = 72) were included in the study. Neurobehavioral changes were assessed using Childhood Psychopathological Measurement Schedule (CPMS) and BLL were measured by Graphite Furnace Atomic Absorption Spectrophotometry (GFAAS). BDNF mRNA expression and serum BDNF levels were assessed by Real-Time PCR and ELISA, respectively. ResultsMedian BLL was 4.95 μg/dL (IQR = 4.47), very close to the recommended toxic cut off levels (<5 μg/dL). BLLs had a direct correlation with both CPMS scores and BDNF expression. Depression was found to be significantly higher in boys than in girls with high BLLs. BDNF mRNA expression and serum BDNF levels were higher among children with high BLL, although not to significant levels. ConclusionWe report a significant association of neurobehavioral changes with the prevalence of high Pb levels in Indian children. Additionally significant correlation of BDNF with BLL in these children suggests a causal role of BDNF in Pb induced neurological damage.

Working memory moderates the relation between the brain-derived neurotropic factor (BDNF) and psychotherapy outcome for depression

BackgroundInsight into patient characteristics that predict response to treatment for major depressive disorder (MDD) may help to personalize treatment and improve outcomes. One mechanism that has been linked to the success of treatment for MDD is brain-derived neurotropic factor (BDNF). BDNF is implicated in learning and memory and may play a role in the effects of psychotherapy that involves changing cognitions and behaviors. In addition, only in individuals with low BDNF, low working memory capacity has been associated with increased symptoms of depression. However, the role of BDNF and working memory capacity in psychotherapy outcome is unclear. The aim of this study was to investigate the role of BDNF and its interaction with working memory capacity in psychotherapy outcomes for MDD. MethodAdult patients with MDD were randomized to weekly or twice weekly sessions of cognitive behavioral therapy or interpersonal psychotherapy. BDNF Val66Met polymorphism (rs6265) (n = 138) was defined and serum BDNF was quantified before (n = 138) and after psychotherapy (n = 82). ResultsBaseline serum BDNF and the Val66Met polymorphism were not associated with outcome and associations did not differ between treatment conditions. Working memory capacity significantly moderated the relation between baseline serum BDNF and outcome: high serum BDNF at baseline was related to less depressive symptoms following psychotherapy in the presence of high working memory capacity, but not low working memory capacity. DiscussionThese findings, if replicated, might indicate that while BDNF may not be related to psychotherapy outcomes in general, they may play a role in the presence of specific learning processes such as working memory capacity.

Effect Of Heat On Serum And Plasma Brain-derived Neurotropic Factor During Aerobic Exercise

Exercise has been found to promote the release of brain-derived neurotropic factor (BDNF). Literature suggests that BDNF is upregulated in the periphery post aerobic exercise. There is evidence that shows BDNF plays a role in temperature regulation, however, it is still unclear if BDNF will rise in the heat as compared to thermoneutral conditions following aerobic exercise. Evidence has also shown that plasma and serum BDNF may be independent of each other. Therefore, investigating this difference may lead to a better understanding of the post aerobic exercise BDNF response. PURPOSE: The purpose of this study was to examine temperature related effects on BDNF during aerobic exercise in different environmental conditions along with differences between serum and plasma BDNF. METHODS: Six recreationally active college aged men (26 ± 3 years) completed a VO2max test (48.6 ± 5.7 mL/kg/min) and performed experimental trials in 35°C at 45% humidity (HT/MH) and 22°C at 45% humidity (MT/MH). During each trial, participants cycled for 60-minutes at 60% of VO2max, rested for 15-minutes, cycled until exhaustion at 90% VO2max, then recovered for 60-minutes. Blood was obtained before exercise (PRE), after 60 minutes of cycling (60), after the TTE (90), and after recovery (REC). Serum and plasma BDNF were assessed via ELISA, while data was analyzed using a mixed model regression, with significance defined as α<0.05. RESULTS: There was no significant condition by time interaction (F = 0.602, p = 0.618) nor main effect of condition (F = 1.792, p = 0.189) or time (F = 1.949, p = 0.139) for serum BDNF concentrations. There was also no significant condition by time interaction (F = 0.272, p = 0.845) nor main effect of condition (F = 0.415, p = 0.523) or time (F = 1.070, p = 0.373) for plasma BDNF concentrations. CONCLUSIONS: This data suggests high temperature does not have an effect on the BDNF response in serum or plasma concentrations. Nor does this study give evidence to an upregulation of BDNF concentrations due to aerobic exercise, though further work is warranted. This study was partially funded by the Kent State University Research Council.

Brain Derived Neurotropic Factor Response To Aerobic Exercise In The Cold

PURPOSE: To examine changes in brain derived neurotropic factor (BDNF) concentration in both plasma and serum following exercise in the cold. METHODS: Six recreationally active men (26 ± 3 yrs; 180.3 ± 5.8 cm; 85.3 ± 8.4 kg; 48.6 ± 5.7 ml·kg−1·min−1) completed an exercise protocol under two conditions: moderate temperature (MT; 23°C/45%RH) and low temperature (5°C). The protocol consisted of a 60-minute cycling trial at 60% VO2max, a 15-minute rest, and a time-to-exhaustion trial at 90% VO2max (TTE). Blood was collected before (T1) and after (T2) the 60-minute trial, immediately after TTE (T3), and one hour post-TTE. Plasma and serum concentrations of BDNF were measured via ELISA. Changes were analyzed using separate condition by time mixed-model regression for each dependent variable. RESULTS: No significant condition × time interaction (F = 1.626, p = 0.201) or main effect of time (F =0.626, p = 0.603) was observed for changes in serum BDNF concentrations; however, a significant main effect of condition (F = 7.685, p = 0.009) was observed. When collapsed across time, serum BDNF concentration was significantly lower during LT (2718.8 ± 1172.2 pg/mL) compared to MT (7240.5 ± 1134.2 pg/mL; p = 0.009). No significant condition × time interaction (F = 0.117, p =0.950), main effect of time (F =0.511, p = 0.677) nor main effect of condition (F = 0.000, p = 0.988) was observed for changes in plasma BDNF concentrations. CONCLUSIONS: The results of this study suggest that exercise in a cold environment (5°C) blunts serum BDNF concentration. However, plasma concentrations of BDNF were not affected by environmental condition nor exercise. Previous research has found no relationship between serum and plasma BDNF, suggesting that these are independent measures of diverse physiological relevance. Peripheral BDNF is predominantly stored in platelets (~99%), with only a small amount of free BDNF present in plasma. Due to the smaller amount of platelet-associated BDNF in plasma, plasma concentrations of BDNF may reflect the amount of free BDNF. Therefore, exercise in a cold environment may decrease BDNF release from platelets while having no effect on free BDNF. This study was partially funded by the Kent State University Research Council.

Circulating Brain Derived Neurotropic Factor (BDNF) In Response To Three-day Ultra-endurance Racing

Cardiovascular exercise is known to exert a variety of positive physiological and psychological benefits on neurocognitive function, glucose and fatty acid metabolism, and muscle recovery. Many of these effects are thought to be mediated by brain derived neurotropic factor (BDNF), a neurotropin produced both centrally and peripherally. The fate of BDNF during prolonged endurance exercise is unknown and may be implicated to mitigate potential negative consequences to ultra-endurance racing. PURPOSE: To investigate the effects of a three-day ultra-endurance triathlon on serum BDNF concentrations pre- and post-race. METHODS: Twenty triathletes (age: 40 ± 8.8 yrs) who competed in the 2015 (N=13 men, 3 women) and 2017 (N=3 men, 1 woman) Ultraman Florida triathlon participated in the present study. Blood samples were collected 24-36 hrs pre-race and within 12 hrs post-race. Serum BDNF levels were measured via ELISA. A paired sample t-test was used to evaluate differences between pre- and post-race BDNF concentrations. Values are reported as mean ± SD with significance accepted as p<0.05. RESULTS: BDNF significantly increased from pre- to post- race (0.17 ± 0.9 pg/mL vs. 0.23 ± 0.14 pg/mL; +9.6%; p<0.05). CONCLUSIONS: For the first time, BDNF is shown to significantly increase after a three-day ultra-endurance race. These findings may indicate that BDNF concentrations are elevated to potentially counteract any negative consequences derived from ultra-endurance exercise. The influence of both duration and intensity of exercise on BDNF concentrations need to be further elucidated due to its array of positive implications on cognitive and physical function and recovery from prolonged endurance exercise. Supported by the International Society of Sports Nutrition and Florida State University.

Relationships Between Serum Osteocalcin, Brain Derived Neurotrophic Factor and Subjective Stress in People With and Without Depression and Type 2 Diabetes Mellitus

In mice, bone-derived hormone osteocalcin is implicated in metabolic function, susceptibility to chronic unpredictable mild stress, and the acute stress response. Altered serum brain-derived neurotropic factor (BDNF) has been observed in depression and after acute stress. Here, we assess relationships between osteocalcin, BDNF, perceived stress and depression, in people with type 2 diabetes mellitus (T2DM).

The Effect of High- and Low-Frequency Repetitive Transcranial Magnetic Stimulation Therapy on Serum Brain-Derived Neurotropic Factor Level and Motor Ability in Ischemic Stroke Patients: A Single-Center Study

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is widely used in various neurological cases. rTMS is an effective method of restoration in patients with disability due to central nervous system disorder.&#x0D; AIM: This study aimed to determine the effect of high and low frequency of rTMS on serum brain-derived neurotropic factor (BDNF) levels and motoric abilities in ischemic stroke patients.&#x0D; METHODS: The study design was an experiment with a purposive sampling consecutive on 27 samples with the onset of ischemic stroke 6 months. The study was conducted from February to October 2018; samples were recruited from Neurology Ward of Wahidin Sudirohusodo hospital and its affiliating centers. The serial of rTMS intervention was delivered in “Brain” Clinic center. After fulfilling the inclusion criteria and the initial examination of serum BDNF and motor ability, samples were randomly divided into two groups, intervention group who received standard therapy with rTMS therapy (n = 14) and the control group who only received standard therapy (n = 13). rTMS was given for 2 min frequency of 1 Hertz (Hz) contralesion and 5 Hz ipsilesion every day for 10 days. Assessment of serum BDNF levels and motor skills was conducted on days 1 and 10 of the study. Serum BDNF levels were measured by the monoclonal antibody ELISA technique while motor skills were measured based on the score of the Stroke Rehabilitation Assessment of Movement (STREAM). Serum BDNF values and the STREAM delta score were compared between the two groups of samples.&#x0D; RESULTS: The results showed significant changes only occurred in motor abilities in both groups of samples after 10 days of rTMS therapy with the Wilcoxon test (p &lt; 0.5). The Mann–Whitney U-test showed a more significant change (p &lt; 0.5) in the treatment group than in the control (p = 0.5).&#x0D; CONCLUSION: rTMS has an effect on improving motor ability in ischemic stroke patients. This change in motor abilities is not related to serum BDNF levels in this study.

Brain Derived Neurotropic Factors in Speed vs. Inclined Treadmill in Young Adult Healthy Male With Occult Balance Disorder.

Background: There is an increase in fall risk among elders and young adults consecutively due to various causes. Occult balance disorder may be among the abnormal causes of falling in young adults as well as elders. The One Leg Stance (OLS) test is used to diagnose this balance performance; it’s a proven test to measure static balance function which would lead to dynamic balance function. It has been proven that aside from cardiopulmonary exercises, treadmill workout can be used as a dynamic balance exercise. The Brain Derived Neurotropic Factor (BDNF) increases balance function through the treadmill exercise (the inclination and speed). This hormone is one of the tropical hormones generated in neurons, muscles, hematopoietic tissue and it is characterized by neurons morphology regulation and neuroplasticity.Materials and Methods: We divided 20 healthy young adult men to work out on inclination and speed groups treadmill exercise. The workout lasted for 2 weeks. We immediately observed the effect of exercise on serum BDNF as two tests were taken on before and 30 min after the workout.Result: There were significant increases of pre-exercise serum BDNF level in speed group between the first and the last exercise (p = 0.001), post-exercise between the first day and the last exercise (p = 0.001). No significant increase of serum BDNF in speed group pre- and post-exercise on the first exercise (p = 0.159), pre- and post-exercise on the last exercise (p = 0.892). There was no significant increase in serum BDNF in inclination group on all parameters (p > 0.05). The serum BDNF is actually a neurotropic factor that affects not just the neuronal system, but also molecular energy and metabolism regulation. This serum is dependent on the aerobic capacity, lactate production, muscle calcium uptake, and muscle fiber type used in exercises. Furthermore, the serum BDNF is increased by treadmill exercises in escalated speed.Conclusion: Treadmill exercises with average speed escalation increase the serum BDNF.

Effects of enalapril and losartan alone and in combination with sodium valproate on seizures, memory, and cardiac changes in rats

PurposeCardiac changes accompanying seizures may be responsible for sudden unexpected death in epilepsy (SUDEP), and drugs with antiseizure and favorable cardiovascular profile could be beneficial. The effect of losartan and enalapril alone and in combination with sodium valproate on seizures, cognition, cardiac histopathology, and serum brain-derived neurotropic factor (BDNF) levels were determined. MethodsMale “Wistar” rats (200–250 g) were administered enalapril (20 mg/kg, intraperitoneally (i.p.)) and losartan (10 mg/kg, i.p.) daily and simultaneously subjected to pentylenetetrazole (PTZ)-kindling (PTZ 30 mg/kg, i.p., every alternate day). Enalapril and losartan were injected 45 & 120 min before seizure stimuli. In another set of experiments, sodium valproate (150 mg/kg, i.p.) alone or in combination with enalapril (20 mg/kg, i.p.) and losartan (10 mg/kg, i.p.) were administered daily during induction of kindling. The effect on seizures and behavior were noted; rats were sacrificed, and blood and hearts were collected for further analysis, i.e., BDNF levels, heart weight–body weight (HWBW) ratio, and cardiac histopathology. ResultsLosartan, but not enalapril, suppressed the seizure score in PTZ kindling. Sodium valproate alone or in combination with losartan or enalapril prevented kindled seizures. Sodium valproate per se caused cognitive impairment, which was prevented on combining with losartan or enalapril. A decrease in HWBW ratio was observed only in enalapril group (p value = 0.02). Kindling led to cardiac ischemic changes, which could be prevented by losartan and sodium valproate. Serum BDNF level was decreased in PTZ (p value = 0.02) and sodium valproate per se group (p value = 0.04), but sodium valproate could reverse the PTZ-induced decrease in serum BDNF level. ConclusionThe use of losartan with sodium valproate in epilepsy may prevent the cognitive and cardiac sequelae of seizures. The BDNF levels as a marker for cardiovascular risk in persons with epilepsy (PWE) needs to be explored further.

Effect of acupuncture and moxibustion on serum brain-derived neurotropic factor level, C-reactive protein, and zinc level in patients with depression

Objectives: To apply the acupuncture and moxibustion to the treatment of patients with depression and study the serum brain-derived neurotropic factor (BDNF) level, C-reactive protein (CRP), and zinc level in the patients. Methods: Thirty-five patients with depression treated in our hospital were selected as the research individuals, and they were randomly divided into the control group and the observation group. Seventeen patients in the control group were treated with head massage and 18 patients in the observation group were treated with acupuncture. The levels of BDNF, CRP, and zinc were measured and recorded by enzyme-linked immunosorbent assay. Results: The levels of BDNF in serum BDNF in the control group were significantly higher than those in the control group, and there was a significant difference between the two groups in serum BDNF levels (P

P2551Low serum brain-derived neurotropic factor may predict poor response to cardiac rehabilitation in patients with cardiovascular disease

P2551Low serum brain-derived neurotropic factor may predict poor response to cardiac rehabilitation in patients with cardiovascular disease

The effect of bilateral low-frequency rTMS over dorsolateral prefrontal cortex on serum brain-derived neurotropic factor and serotonin in patients with generalized anxiety disorder

To investigate the effect of bilateral low-frequency repetitive transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex on serum brain-derived neurotropic factor (BDNF) and serotonin (5-HT) in patients with generalized anxiety disorders (GAD). As compared with before treatment, the HARS score in patients markedly decreased after treatment, and the levels of serum BDNF and 5-HT were significantly higher. Pearson correlation analysis revealed that the increase in the level of serum 5-HT was positively associated with the increase of the level of serum BDNF, and the change of anxiety score was negatively associated with the change of the level of serum BDNF and 5-HT. The results suggested that alleviation of GAD by bilateral low-frequency rTMS may be involved in the increase of the level of BDNF and the release of 5-HT in the brain.

The effects of repeated antibiotic administration to juvenile BALB/c mice on the microbiota status and animal behavior at the adult age

Recent studies carried on germ –free (GF) animal models suggest that the gut microbiota (GM) may play a role in the regulation of anxiety, mood, and cognitive abilities such as memory and learning processes. Consistently, any treatment disturbing the gut microbiota, including the overuse of antibiotics, may influence the brain functions and impact behavior. In the present study, to address this issue, two wide-spectrum antibiotics (ampicillin and cefoperazone, 1 g/l) were repeatedly applied throughout a 6-week period to initially 21-day-old male BALB/c mice. Antibiotics were administered separately or in a mixed fashion. On the completion of the antibiotic treatment, all mice were subjected to the behavioral tests. The serum levels of corticosterone and brain-derived neurotropic factor (BDNF) were assessed. Gut microbiota profiles were obtained by using denaturing gradient gel electrophoresis system, DGGE, from fecal samples. Ampicillin had a greater impact on both, gut microbiota composition and mice behavior compared to cefoperazone. All antibiotic-treated groups manifested a decrease in the locomotor activity and reduced recognition memory. However, the ampicillin-treated groups showed a higher anxiety level as assessed by the open field and the elevated plus maze tests and an increased immobility (behavioral despair) in the forced swim test. Obtained results evidently show that in mice, a repeated antibiotic treatment applied during adolescence, parallel to the changes in GM, affects locomotor activity, affective behavior and cognitive skills in young adults with ampicillin specifically enhancing anxiety- and depressive-like responses. Lower levels of serum BDNF were not associated with cognitive impairment but with changes in affective-like behaviors. Repeated administration of neither ampicillin nor cefoperazone affected basal serum corticosterone levels. This is one of the few studies demonstrating changes in a behavioral phenotype of young-adult subjects who were previously exposed to a repeated antibiotic treatment.

Serum brain-derived neurotrophic factor level and exercise tolerance complement each other in predicting the prognosis of patients with heart failure

Brain-derived neurotropic factor (BDNF) is a myokine that plays a key role in regulating survival, growth, and maintenance of neurons. We investigated whether the serum BDNF level at discharge could predict the prognosis in patients with heart failure (HF). Furthermore, we aimed to examine the relationship between this myokine and exercise tolerance. We prospectively enrolled 94 patients who were hospitalized for worsening HF and had cardiac rehabilitation. At discharge, the serum BDNF level of all patients was measured using a commercial ELISA kit and they underwent a cardiopulmonary exercise test to measure peak oxygen uptake (peak VO2). Correlation was not observed between BDNF and peak VO2. Kaplan-Meier analysis demonstrated that cardiac death or rehospitalization owing to worsening HF was significantly higher in the low BDNF group (p = 0.023). The combination of peak VO2 and BDNF levels led to the identification of subgroups with significantly different probabilities of events (p = 0.005). In particular, in the low BDNF and low peak VO2 group, the frequency of rehospitalization within half a year after discharge was much higher than that in other groups. Multivariate analysis found BDNF as an independent factor of adverse events (hazard ratio 0.956; 95% confidence interval 0.911-0.999; p = 0.046). The serum BDNF level at discharge may be a useful biomarker of the prognosis in patients with HF. Furthermore, combining BDNF and peak VO2 may be useful for predicting early cardiac events.

Levels of Serum Brain-Derived Neurotropic Factor in Individuals at Ultra-High Risk for Psychosis-Findings from the Longitudinal Youth at Risk Study (LYRIKS).

BackgroundIdentifying biomarkers to enrich prognostication and risk predictions in individuals at high risk of developing psychosis will enable stratified early intervention efforts. Brain-derived neurotrophic factor has been widely studied in schizophrenia and in first-episode psychosis with promising results. The aim of this study was to examine the levels of serum brain-derived neurotrophic factor between healthy controls and individuals with ultra-high risk of psychosis.MethodsA sample of 106 healthy controls and 105 ultra-high risk of psychosis individuals from the Longitudinal Youth at Risk Study was included in this study. Ultra-high risk of psychosis status was determined using the Comprehensive Assessment of At-Risk Mental State at recruitment. Calgary Depression Scale for Schizophrenia was used to assess the severity of depression. All participants were followed up for 2 years, and ultra-high risk of psychosis remitters were defined by ultra-high risk of psychosis individuals who no longer fulfilled Comprehensive Assessment of At-Risk Mental State criteria at the end of the study period. Levels of brain-derived neurotrophic factor were measured in the serum by enzyme-linked immunosorbent assay method.ResultsThe ultra-high risk of psychosis group had significantly higher baseline levels of serum brain-derived neurotrophic factor compared with the control group (3.7 vs 3.3 ng/mL, P=.018). However, baseline levels of serum brain-derived neurotrophic factor did not predict the development of psychosis (OR=0.64, CI=0.40–1.02) or remission (OR=0.83, CI=0.60–1.15) from ultra-high risk of psychosis status.ConclusionFindings from our study did not support a role for serum brain-derived neurotrophic factor in predicting outcomes in ultra-high risk of psychosis individuals. However, the finding of higher levels of serum brain-derived neurotrophic factor in ultra-high risk of psychosis individuals deserves further study.

Aerobic Exercise as an Adjuvant to Aphasia Therapy: Theory, Preliminary Findings, and Future Directions

PurposeThis study investigated whether participation in aerobic exercise enhances the effects of aphasia therapy, and the degree to which basal serum brain-derived neurotropic factor (BDNF) concentrations fluctuate after the beginning of aerobic exercise or stretching activities in individuals with poststroke aphasia. MethodsThe study used a single-subject, multiple-baseline design. Seven individuals with chronic poststroke aphasia participated in 2 Blocks of aphasia therapy: aphasia therapy alone (Block 1), followed by aphasia therapy with the addition of aerobic activity via bicycle ergometer (n = 5) or stretching (n = 2) (Block 2). Serum BDNF concentrations from blood draws were analyzed in 4 participants who exercised and in 1 participant who stretched. FindingsThree of the five exercise participants demonstrated larger Tau-U effects when aphasia therapy was paired with aerobic exercise, whereas 1 of the 2 stretching participants demonstrated a larger effect size when aphasia therapy was paired with stretching. Group-level comparisons revealed a greater overall increase in effect size in the aerobic exercise group, as indicated by differences in Tau-U weighted means. BDNF data showed that all 4 exercise participants demonstrated a decrease in BDNF concentrations during the first 6 weeks of exercise and an increase in BDNF levels near or at baseline during the last 6 weeks of exercise. The stretching participant did not show the same pattern. ImplicationsAdditional research is needed to understand the mechanism of effect and to identify the factors that mediate response to exercise interventions, specifically the optimal dose of exercise and timing of language intervention with exercise. ClinicalTrials.gov identifier: NCT01113879.