Changes In Serum Brain-derived Neurotrophic Factor Research Articles

Elevations in serum brain-derived neurotrophic factor following occupational heat stress are not influenced by age or common chronic disease

ABSTRACT With global warming, workers are increasingly exposed to strenuous occupations in hot environments. Given age- and disease-associated declines in thermoregulatory function, older workers are at an elevated risk of developing heat-related injuries. Brain-derived neurotrophic factor (BDNF) is thought to confer neuroprotection during acute exercise, however, the influence of environmental heat on BDNF responses during prolonged work remains unclear. Therefore, we evaluated serum BDNF concentrations before and after 180 min of moderate-intensity treadmill walking (200 W/m2) and after 60 min of post-exercise recovery in temperate (wet-bulb globe temperature (WBGT) 16°C) and hot (WBGT 32°C) environments in 13 healthy young men (mean [SD; 22 [3] years), 12 healthy older men (59 [4] years), 10 men with hypertension (HTN) (60 [4] years), and 9 men with type 2 diabetes (T2D) (60 [5] years). In the temperate condition, all but one participant (1 HTN) completed the 180 min of exercise. While exercise tolerance in the heat was lower in older men with HTN (117 min [45]) and T2D (123 min [42]) compared to healthy older men (159 min [31]) (both p ≤ 0.049), similar end-exercise rectal temperatures (38.9°C [0.4]) were observed across groups, paralleled by similar elevations in serum BDNF across groups at end-exercise (+1106 pg/mL [203]) and end-recovery (+938 pg/mL [146]; all p ≤ 0.01) in the heat. No changes in serum BDNF were observed in the temperate condition. Our findings indicate similar BDNF responses in individuals with HTN or T2D compared to their healthy counterparts, despite exhibiting reduced tolerance to heat.

The Serum Brain-Derived Neurotrophic Factor Increases in Serotonin Reuptake Inhibitor Responders Patients with First-Episode, Drug-Naïve Major Depression

Brain-derived neurotrophic factor (BDNF) is a growth factor synthesized in the cell bodies of neurons and glia, which affects neuronal maturation, the survival of nervous system, and synaptic plasticity. BDNF play an important role in the pathophysiology of major depression (MD). The serum BDNF levels changed over time, or with the improvement in depressive symptoms. However, the change of serum BDNF during pharmacotherapy remains obscure in MDD. In particular, the changes in serum BDNF associated with pharmacotherapy have not yet been fully elucidated. The present study aimed to compare the changes in serum BDNF concentrations in first-episode, drug-naive patients with MD treated with antidepressants between treatment-response and treatment-nonresponse groups. The study included 35 inpatients and outpatients composed of 15 males and 20 females aged 36.7 ± 6.8 years at the Department of Psychiatry of our University Hospital. All patients met the DSM-5 diagnostic criteria for MD. The antidepressants administered included paroxetine, duloxetine, and escitalopram. Severity of depressive state was assessed using the 17-item HAMD before and 8 weeks after drug administration. Responders were defined as those whose total HAMD scores at 8 weeks had decreased by 50% or more compared to those before drug administration, while non-responders were those whose total HAMD scores had decreased by less than 50%. Here we showed that serum BDNF levels were not significantly different at any point between the two groups. The responder group, but not the non-responder group, showed statistically significant changes in serum BDNF 0 and serum BDNF 8. The results suggest that the changes of serum BDNF might differ between the two groups. The measurement of serum BDNF has the potential to be a useful predictor of pharmacotherapy in patients with first-episode, drug-naïve MD.

The Effects of Four Weeks of Chiropractic Spinal Adjustments on Blood Biomarkers in Adults with Chronic Stroke: Secondary Outcomes of a Randomized Controlled Trial.

Certain blood biomarkers are associated with neural protection and neural plasticity in healthy people and individuals with prior brain injury. To date, no studies have evaluated the effects chiropractic care on serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor-II (IGF-II) and glial cell-derived neurotrophic factor (GDNF) in people with stroke. This manuscript reports pre-specified, exploratory, secondary outcomes from a previously completed parallel group randomized controlled trial. We evaluated differences between four weeks of chiropractic spinal adjustments combined with the usual physical therapy (chiro + PT) and sham chiropractic with physical therapy (sham + PT) on resting serum BDNF, IGF-II and GDNF in 63 adults with chronic stroke. Blood samples were assessed at baseline, four weeks (post-intervention), and eight weeks (follow-up). Data were analyzed using a linear multivariate mixed effects model. Within both groups there was a significant decrease in the mean log-concentration of BDNF and IGF-II at each follow-up, and significant increase log-concentration of GDNF at eight-weeks' follow-up. However, no significant between-group differences in any of the blood biomarkers at each time-point were found. Further research is required to explore which factors influence changes in serum BDNF, IGF-II and GDNF following chiropractic spinal adjustments and physical therapy.

Gene- and Gender-Related Decrease in Serum BDNF Levels in Alzheimer’s Disease

Brain-derived neurotrophic factor (BDNF) has a protective role in Alzheimer's disease (AD). Oxidative stress and inflammatory cytokines are potentially implicated in AD risk. In this study, BDNF was detected in serum of AD and mild cognitive impairment (MCI) patients and investigated in association with gene polymorphisms of BDNF (Val66Met and C270T), of some oxidative stress-related genes (FOXO3A, SIRT3, GLO1, and SOD2), and of interleukin-1 family genes (IL-1α, IL-1β, and IL-38). The APOE status and mini-mental state examination (MMSE) score were also evaluated. Serum BDNF was significantly lower in AD (p = 0.029), especially when comparing the female subsets (p = 0.005). Patients with BDNFVal/Val homozygous also had significantly lower circulating BDNF compared with controls (p = 0.010). Moreover, lower BDNF was associated with the presence of the T mutant allele of IL-1α(rs1800587) in AD (p = 0.040). These results were even more significant in the female subsets (BDNFVal/Val, p = 0.001; IL-1α, p = 0.013; males: ns). In conclusion, reduced serum levels of BDNF were found in AD; polymorphisms of the IL-1α and BDNF genes appear to be involved in changes in serum BDNF, particularly in female patients, while no effects of other gene variants affecting oxidative stress have been found. These findings add another step in identifying gender-related susceptibility to AD.

Serum brain-derived neurotrophic factor remains elevated after long term follow-up of combat veterans with chronic post-traumatic stress disorder

Attempts to correlate blood levels of brain-derived neurotrophic factor (BDNF) with post-traumatic stress disorder (PTSD) have provided conflicting results. Some studies found a positive association between BDNF and PTSD diagnosis and symptom severity, while others found the association to be negative. The present study investigated whether serum levels of BDNF are different cross-sectionally between combat trauma-exposed veterans with and without PTSD, as well as whether longitudinal changes in serum BDNF differ as a function of PTSD diagnosis over time. We analyzed data of 270 combat trauma-exposed veterans (230 males, 40 females, average age: 33.29 ± 8.28 years) and found that, at the initial cross-sectional assessment (T0), which averaged 6 years after the initial exposure to combat trauma (SD=2.83 years), the PTSD positive group had significantly higher serum BDNF levels than the PTSD negative controls [31.03 vs. 26.95 ng/mL, t(268) = 3.921, p < 0.001]. This difference remained significant after excluding individuals with comorbid major depressive disorder, antidepressant users and controlling for age, gender, race, BMI, and time since trauma. Fifty-nine of the male veterans who participated at the first timepoint (T0) were re-assessed at follow-up evaluation (T1), approximately 3 years (SD=0.88 years) after T0. A one-way ANOVA comparing PTSD positive, "subthreshold PTSD" and control groups revealed that serum BDNF remained significantly higher in the PTSD positive group than the control group at T1 [30.05 vs 24.66 ng/mL, F(2, 56)= 3.420, p = 0.040]. Serum BDNF levels did not correlate with PTSD symptom severity at either time point within the PTSD group [r(128) = 0.062, p = 0.481 and r(28) = 0.157, p = 0.407]. Serum BDNF did not significantly change over time within subjects [t(56) = 1.269, p = 0.210] nor did the change of serum BDNF from T0 to T1 correlate with change in PTSD symptom severity within those who were diagnosed with PTSD at T0 [r(27) = −0.250, p = 0.192]. Our longitudinal data are the first to be reported in combat PTSD and suggest that higher serum BDNF levels may be a stable biological characteristic of chronic combat PTSD independent of symptom severity.

Improvement of cognitive function, glucose and lipid homeostasis and serum osteocalcin levels by liraglutide in diabetic rats.

Glucose and lipid abnormalities, oxidative stress (OXS) and reduced brain-derived neurotrophic factor (BDNF) are involved in cognitive dysfunction in diabetes. Glucagon like peptide 1 (GLP1) receptors modulate glucose and lipid metabolism, cognitive function and serum osteocalcin. On the other hand, osteocalcin modulates cognitive function and glucose and lipid metabolism. This study investigated whether the GLP 1 agonist liraglutide improves cognitive function via modulation of serum osteocalcin and glucose and lipid metabolism. Effects of 4weeks liraglutide treatment (100µg/Kg/d and 300µg/Kg/d) on changes in cognitive function and bone homeostasis, induced by high fat diet/low-dose streptozotocin (HFD-STZ), were determined in rats. Cognitive function was assessed using Morris water maze (MWM) test. Serum and bone biochemical parameters were determined. Liraglutide dose-dependently improved cognitive function in diabetic rats (reduced escape latency, and increased time spent in target quadrant in MWM test, compared to diabetic control). Glucose and lipid abnormalities and the associated changes in serum BDNF and oxidative stress makers were improved. Serum BDNF and glutathione were significantly increased, whereas malondialdehyde level was reduced. Serum osteocalcin was significantly increased and correlated with improvement in cognitive dysfunction. Serum and bone receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin ratios were significantly reduced by liraglutide treatment. Improvement of cognitive dysfunction by liraglutide involves modulation of glucose and lipid metabolism and serum osteocalcin. GLP1 agonists may provide an alternative metabolic approach for cognitive dysfunction in diabetes.

The placenta protects the fetal circulation from anxiety-driven elevations in maternal serum levels of brain-derived neurotrophic factor

Brain-derived neurotrophic factor (BDNF) plays crucial roles in brain function. Numerous studies report alterations in BDNF levels in human serum in various neurological conditions, including mood disorders such as depression. However, little is known about BDNF levels in the blood during pregnancy. We asked whether maternal depression and/or anxiety during pregnancy were associated with altered serum BDNF levels in mothers (n = 251) and their new-born infants (n = 212). As prenatal exposure to maternal mood disorders significantly increases the risk of neurological conditions in later life, we also examined the possibility of placental BDNF transfer by developing a new mouse model. We found no association between maternal symptoms of depression and either maternal or infant cord blood serum BDNF. However, maternal symptoms of anxiety correlated with significantly raised maternal serum BDNF exclusively in mothers of boys (r = 0.281; P = 0.005; n = 99). Serum BDNF was significantly lower in male infants than female infants but neither correlated with maternal anxiety symptoms. Consistent with this observation, we found no evidence for BDNF transfer across the placenta. We conclude that the placenta protects the developing fetus from maternal changes in serum BDNF that could otherwise have adverse consequences for fetal development.

Exercise-Induced Elevated BDNF Level Does Not Prevent Cognitive Impairment Due to Acute Exposure to Moderate Hypoxia in Well-Trained Athletes.

Exposure to acute hypoxia causes a detrimental effect on the brain which is also manifested by a decrease in the ability to perform psychomotor tasks. Conversely, brain-derived neurotrophic factor (BDNF), whose levels are elevated in response to exercise, is a well-known factor in improving cognitive function. Therefore, the aim of our study was to investigate whether the exercise under hypoxic conditions affects psychomotor performance. For this purpose, 11 healthy young athletes performed a graded cycloergometer exercise test to volitional exhaustion under normoxia and acute mild hypoxia (FiO2 = 14.7%). Before, immediately after exercise and after a period of recovery, choice reaction time (CRT) and number of correct reactions (NCR) in relation to changes in serum BDNF were examined. Additionally, other selected factors which may modify BDNF production, i.e., cortisol (C), nitrite, catecholamines (adrenalin-A, noradrenaline-NA, dopamine-DA, serotonin-5-HT) and endothelin-1 (ET-1), were also measured. Exercise in hypoxic conditions extended CRT by 13.8% (p < 0.01) and decreased NCR (by 11.5%) compared to rest (p < 0.05). During maximal workload, NCR was lower by 9% in hypoxia compared to normoxia (p < 0.05). BDNF increased immediately after exercise in normoxia (by 29.3%; p < 0.01), as well as in hypoxia (by 50.0%; p < 0.001). There were no differences in BDNF between normoxia and hypoxia. Considering the fact that similar levels of BDNF were seen in both conditions but cognitive performance was suppressed in hypoxia, acute elevation of BDNF did not compensate for hypoxia-induced cognition impairment. Moreover, neither potentially negative effects of C nor positive effects of A, DA and NO on the brain were observed in our study.

Physical exercise interventions have no effect on serum BDNF concentration in older adults living in long-term nursing homes.

Physical exercise protects against age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) may mediate some of the cognitive benefits of physical exercise, but the effect of physical exercise on serum BDNF is unclear. Indeed, differential findings have been reported depending on the characteristics of the participants and the intensity, duration, and type of exercise. The aim of this study was to determine whether three different physical exercise interventions alter serum BDNF levels in older adults living in long-term nursing homes (LTNHs) and whether changes in physical, cognitive, and dual-task performance are related to changes in serum BDNF. LTNH study participants (n=126) were randomly assigned to multicomponent or dual-task training or a walking program and serum BDNF levels were analyzed by ELISA. We also assessed physical, cognitive, and dual-task parameters. Neither the multicomponent, dual-task, nor walking exercise programs caused changes in serum BDNF concentration in older adults living in LTNHs. Changes in BDNF during the interventions were not significantly associated with modifications in physical, cognitive or dual-task performance parameters. Our results provide new evidence clarifying the relationship between physical and cognitive exercise and BDNF.

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

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

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

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

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

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

Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial.

Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).

Investigation of Serum Brain Derived Neurotrophic Factor Levels in Children and Adolescents Aged 12 to 18 Years with Depressive Disorder

Objective: It has been suggested that the neuroplastic processis associated with the pathogenesis of psychiatric disorders including depressive disorder. It is thought that brain derived neurotrophic factor (BDNF) is an important factor in neuroplasticity in depressive disorder. BDNF is play an important role in survival of neurons, synaptic plasticity, formation of synaptic connections and neurodevelopment. Insulin like growth factor-1 (IGF-1) is found in various areas of the brain. IGF-1 is involved in brain growth, development and mylination, also in brain plasticity. IGF-1 affect the genesis of neurons, astrocytes, oligodendrocytes and endothelial cells. In this study we aimed to evaluate serum levels of BDNF and IGF-1, which is also accepted as a neurotrophic factor, in children and adolescents between 12-18 years with depressive disorder. Methods: The patient group was composed of 35 subjects (26 females; 9 male), while the control group was composed of 22 subjects (14 females; 8 male). Sociodemographic form, Kovac’s depression scale, and state-trait anxiety inventory were applied to all subjects. Serum BDNF and IGF-1 levels were measured with ELISA. Moreover complete blood count, biochemical tests, thyroid and sex hormones were tested.Results: There was no significant difference between the patient group and the control group in terms of the BDNF and IGF-1 levels (respectively p values 0.547 and 0.968). When the groups divided into female and male subgroups, statistically significant differences were not found again. Moreover age, gender, menstrual states, suicide attempts, suicide thoughts, smoking and Body Mass Index had no effects on the BDNF. There was also no effects on IGF-1 levels, except age. There was negative correlation between age and IGF-1 in all subjects.Conclusion: The results of this study do not support the association of depressive disorder with changes in serum BDNF and IGF-1 levels in children and adolescents. But larger prospective studies are needed to show better the effects of these factors.

Involvement of brain-derived neurotrophic factor in exercise‑induced cardioprotection of post-myocardial infarction rats.

Exercise induces a number of benefits, including angiogenesis in post‑myocardial infarction (MI); however, the underlying mechanisms have not been fully clarified. Neurotrophic brain‑derived neurotrophic factor (BDNF) serves a protective role in certain adult cardiac diseases through its specific receptor, BDNF/NT‑3 growth factors receptor (TrkB). The present study explored the mechanisms by which exercise improves cardiac function, with a focus on the involvement of the BDNF/TrkB axis. MI rats were assigned to Sham, sedentary, exercise, exercise with K252a (aTrkB inhibitor), and exercise with NG‑nitro‑L‑arginine methyl ester (L‑NAME) groups. The exercise group was subjected to 8weeks of treadmill running. The results demonstrated that the rats in the exercise group exhibited increased myocardial angiogenesis and improved cardiac function, which was attenuated by K252a. Exercise induced activation of the BDNF/TrkB axis in the ischaemic myocardium and increased serum BDNF levels were abated by exposure to L‑NAME. Improvements in angiogenesis and left ventricular function exhibited a positive association, with changes in serum BDNF. In the invitro experiments, human umbilical vein endothelial cells were exposed to shear stress (SS) of 12dyn/cm2 to mimic the effects of exercise training on vascular tissue. An increased tube‑forming capacity, and a nitric oxide (NO)‑dependent prolonged activation of the BDNF/TrkB‑full‑length axis over 12h, but not the TrkB‑truncated axis, was observed. The SS‑related angiogenic response was attenuated by TrkB inhibition. Overall, these results demonstrate that exercise confers certain aspects of its cardioprotective effects through the activation of the BDNF/TrkB axis in an NO‑dependent manner, a process in which fluid‑induced SS may serve a crucial role.

Brain-derived neurotrophic factor in serum as an animal welfare indicator of environmental enrichment in pigs

Environment enrichment is a rising topic for animal welfare but measures to identify effective enrichment interventions are lacking. In humans and rodent species, environmental enrichment increases brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the brain. Higher BDNF concentration is ultimately linked to higher stress resilience, and BDNF in the hippocampus enhances learning and memory. In addition, BDNF concentrations in the brain and blood are correlated, offering the opportunity to use peripheral BDNF as a minimally invasive measure of effective enrichment reflecting neural changes. This study investigated changes in serum BDNF following the provision of environmental enrichment to pigs. Pigs were housed in different environments during lactation (enriched vs barren) and after weaning (enriched vs barren), using a 2 × 2 factorial design and the provision of a foraging block as enrichment. Pigs provided with foraging enrichment during lactation or after weaning tended to have higher serum BDNF concentrations than pigs housed in a barren environment, and this effect was significant for pigs enriched during lactation when sampled 5 wk after weaning. Brain-derived neurotrophic factor concentration reduced as the pigs aged from 3 to 11 wk. The measurement of BDNF in serum brings a practical approach to study the effects of environmental enrichment on neurobiological changes in domestic animals. A better understanding of the factors modulating BDNF and its link to welfare states could bring insight into the benefits of stimulating an animal's life.

Both Serum Brain-Derived Neurotrophic Factor and Interleukin-6 Levels Are Not Associated with Therapeutic Response to Lamotrigine Augmentation Therapy in Treatment-Resistant Depressive Disorder

Background/Aims: Serum levels of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) were prospectively monitored in relation with therapeutic response to lamotrigine augmentation therapy in 46 (15 males and 31 females) inpatients with treatment-resistant depressive disorder during an 8-week treatment with lamotrigine using an open-study design. Methods: The subjects were 46 depressed patients who had already shown insufficient response to at least 3 psychotropics including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n = 19), bipolar I disorder (n = 6), and bipolar II disorder (n = 22). The final doses of lamotrigine were 100 mg/day for 26 subjects who were not taking valproate and 75 mg/day for 20 subjects taking valproate, respectively. Depressive symptoms were evaluated by the Montgomery-Åsberg Depression Rating Scale (MADRS) before and after the 8-week treatment. Blood sampling was performed before the start of lamotrigine treatment and at week 8. Serum BDNF and IL-6 levels were measured using quantitative sandwich enzyme immunoassays. Results: No significant changes in serum BDNF or IL-6 levels during the 8-week lamotrigine treatment were observed in the total of subjects, responders or nonresponders. There was no significant correlation between the changes in serum BDNF or IL-6 levels and the percent improvement in MADRS scores in the overall subjects. Conclusion: The present study suggests that the acute effect of lamotrigine augmentation therapy for a major depressive episode is not related to either BDNF or IL-6, at least in patients with treatment-resistant depressive disorder.

Effect of Oxcarbazepine on Serum Brain Derived Neurotrophic Factor in Bipolar Mania: An Exploratory Study.

ObjectiveIn bipolar disorder, serum brain-derived neurotrophic factor (BDNF) level decreases leading to dysfunctions of critical neurotrophic, cellular plasticity and neuroprotective processes. The present study was conducted to evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar mania.MethodsThe present study is a prospective, interventional, open label clinical study conducted on 25 patients of bipolar mania and 25 healthy controls. Detailed history, clinical evaluation including Young Mania Rating Scale (YMRS) scoring and serum BDNF were assessed at baseline for all 50 subjects. The bipolar patients were prescribed tablet oxcarbazepine and followed up after 4 weeks for clinical evaluation and re-estimation of serum BDNF and YMRS scoring.ResultsThe serum BDNF level in bipolar manic patients were compared with healthy controls at baseline and results revealed that there is a significant reduction (p=0.002) in serum BDNF level in bipolar patients. At follow-up after 4 weeks, the mean change in serum BDNF in bipolar group who were on oxcarbazepine monotherapy was found statistically significant (p=0.02) in comparison to healthy controls. In bipolar group, the YMRS score and serum BDNF at baseline have an inverse relation(r=−0.59) whereas change of the YMRS score had a positive correlation (r=0.67) with the change of serum BDNF over 4 weeks.ConclusionIn bipolar mania serum BDNF level is low and it is found to be increased with short term monotherapy with oxcarbazepine.

Stress-induced change in serum BDNF is related to quantitative family history of alcohol use disorder and age at first alcohol use

Previous research in animal models suggests that brain-derived neurotrophic factor (BDNF) is involved in stress-modulated alcohol consumption. However, relatively few studies have investigated this issue in humans, and results of existing studies have been heterogeneous. The primary aim of the current study was to examine the within-subjects effect of acute stress (timed math plus cold pressor) on serum BDNF levels (ΔBDNF: post- minus pre-stress) in healthy social drinkers (N=68, 20 male). A secondary aim was to explore which heritable and environmental factors in our limited sample might exert the greatest influences on ΔBDNF. Importantly, presence versus absence of the BDNF Val66Met polymorphism (rs6265), which has often been discounted in studies of human serum BDNF, was included as a between-subjects control variable in all statistical analyses. Our results indicated that acute stress decreased serum BDNF. Further, multiple regression analyses revealed that quantitative family history of alcohol use disorder (qFH) and age at first alcohol use together accounted for 15% of the variance in ΔBDNF. Thus, the influences of qFH and age at first alcohol use may explain some of the heterogeneity that exists in previous studies of human serum BDNF. These results parallel findings in animal models and suggest that stress-related changes in serum BDNF are influenced by both heritable (qFH) and environmental (early alcohol consumption) factors.

Association between smoking, nicotine dependence, and BDNF Val66Met polymorphism with BDNF concentrations in serum.

Nicotine use is associated with the upregulation of brain-derived neurotrophic factor (BDNF) in serum. An association between smoking and the BDNF Val(66)Met polymorphism has also been found. The aim of this study is to examine the levels of serum BDNF in never-smokers, former smokers, and current smokers-with and without nicotine dependence-and to examine the interaction of the polymorphism and smoking status with serum BDNF. We used baseline serum and gene data of BDNF on 2,088 participants from the Netherlands Study of Depression and Anxiety (NESDA) to investigate smoking-BDNF association while controlling for potential confounding variables. Nicotine dependence was assessed with the Fagerstrom Test for Nicotine Dependence (FTND). Smokers with and without nicotine dependence had higher levels of serum BDNF than former and never-smokers. Nicotine dependence and number of cigarettes smoked per day did not add to the prediction of serum BDNF; however, total number of smoking years was a significant predictor of serum BDNF. There was no association of BDNF Val(66)Met, nor an interaction of this polymorphism and smoking status, with serum BDNF. Current smoking and higher number of smoking years are associated with higher levels of serum BDNF, and this is independent of the BDNF genotype. Nicotine dependence itself is not associated with a further increase or decrease of serum BDNF. Longitudinal investigations that address changes in serum BDNF in incident smokers and/or in quitters may be useful to understand the association of smoking with BDNF.