Plasma Brain-derived Neurotrophic Factor Concentrations Research Articles

Differences In Plasma And Serum BDNF In Response To Acute HIIE

PURPOSE: Circulating concentrations of brain-derived neurotrophic factor (BDNF) are reported to increase with acute exercise in a dose-dependent manner; however, the sources of elevated plasma and serum BDNF may differ as workload increases. Elevated plasma BDNF concentrations are believed to reflect release by the brain, which can indicate positive adaptations in brain health, whereas elevations in serum may reflect increased platelet release by the spleen. The popularity and documented benefits of high intensity interval exercise (HIIE), prompted the aim of this study to clarify the acute effects of low-volume, supramaximal HIIE on circulating BDNF. Furthermore, to examine a possible explanation for the changes in plasma BDNF, irisin, a protein involved in the mechanism linking muscle contraction and hippocampal BDNF release, was measured in plasma. METHODS: Healthy, sedentary males (N=11) participated in HIIE on a cycle ergometer (10 x 20 seconds of maximal pedaling against 5.5% of the subject’s body weight x 10 seconds of rest). Whole blood samples were collected from the antecubital vein prior to, immediately after (POST), and 15 minutes after (15POST) HIIE for BNDF and irisin analyses. RESULTS: At rest, serum BDNF concentrations were nearly 40-fold greater compared to plasma. Although no changes in plasma BDNF were observed after HIIE, serum BDNF increased at POST and 15POST (F (2,40) = 7.277, p = 0.002). Plasma irisin concentrations significantly decreased at POST (p = 0.029). In addition, a positive association between the total change in irisin and total change in plasma BDNF approached significance (r = 0.501, p = 0.097). CONCLUSIONS: These findings demonstrated that this low-volume, supramaximal HIIE protocol was sufficient for elevating serum BDNF, but not adequate for increasing circulating plasma BDNF in sedentary males. These results may suggest that the intensity of physical activity can differentially affect plasma and serum levels of BDNF. Additional research on HIIE volume and the mechanisms underlying BDNF responses (e.g. irisin) is warranted.

Brain-derived neurotrophic factor (BDNF) plasma concentration in patients diagnosed with premature ovarian insufficiency (POI)

Premature ovarian insufficiency (POI) is defined as a cessation of function of ovaries in women younger than 40 years old. Brain-derived neurotrophic factor (BDNF) is a protein critically involved in neuronal growth and metabolism. BDNF also has been shown to be important regulator of oocyte maturation. Recent data show that BDNF can be potentially involved in POI pathology. The aim of the study was to assess the BDNF plasma concentrations in patients diagnosed with idiopathic POI. 23 women diagnosed with POI (age 31 ± 7 years) and 18 (age 31 ± 3) controls were included to the study, matched according to age and body mass index. The BDNF concentrations were measured using competitive enzyme-linked immunosorbent assay (ELISA). Hormonal and metabolic parameters were measured in all individuals, in controls in late follicular phase. The POI group demonstrated lower mean plasma concentrations of BDNF (429.25 ± 65.52 pg/ml) in comparison to healthy controls (479.75 ± 34.75 pg/ml, p = 0.0345). The BDNF plasma concentration correlated negatively (R = −0.79, p < 0.001) with number of months since last menstrual period. There was a positive correlation between BDNF and progesterone in controls. In conclusion, POI patients show significantly lower BDNF plasma concentration and it correlates with the duration of amenorrhea. This observation brings important potential insights to the pathology of POI.

Effect of Physical Activity on Cognitive Development: Protocol for a 15-Year Longitudinal Follow-Up Study

The aim of the study is to investigate the relationship between physical activity as assessed by accelerometers and cognitive development across the human age ranges (from children and adolescents to adults). Additionally, this study seeks to explore whether physical activity contributes to cognitive development via modification of plasma insulin-like growth factor 1 (IGF-1) and brain-derived neurotrophic factor (BDNF). In the study, 500 preschool children (3.5–5.5 years old) are taking part in 6 triennial assessment waves over the span of 15 years. At each wave, participant measures included (a) 7-day physical activity monitoring using ActiGraph's GT3X accelerometers, (b) the evaluation of cognitive development, (c) anthropometric and physical fitness assessments, (d) plasma IGF-1 and BDNF concentrations, and (e) retrospective questionnaires. Linear regression models are used to examine the effect of physical activity on cognitive development; plasma IGF-1 and BDNF concentrations are considered as mediators into data analyses. The results of the study may help to inform future health interventions that utilize physical activity as a means to improve cognitive development in children, adolescents, and adults. Additionally, the study may assist in determining whether the putative effects occur via modification of plasma IGF-1 or BDNF concentrations.

Decreased plasma concentrations of brain-derived neurotrophic factor in preeclampsia

BackgroundPreeclampsia (PE) is a disease characterized by excessive maternal inflammatory response. Early studies suggested that brain-derived neurotrophic factor (BDNF) modulates inflammation. The main objective of this study was to investigate BDNF plasma concentrations in PE women and to compare with BDNF concentrations from normotensive pregnant women. We also investigated the association among the plasma concentrations of BDNF and inflammatory mediators, and maternal clinical features. MethodsBDNF plasma concentrations were measured by ELISA in 38 PE women (17 early onset and 21 late onset) and in 20 normotensive pregnant women (Norm) matched for gestational age (Norm<34weeks: n=8; Norm≥34weeks: n=12). Correlation analyses between laboratory parameters and clinical characteristics were evaluated through Spearman's coefficients. ResultsBDNF concentration was lower in PE women than in normotensive pregnant women, but no difference was detected between the subgroups of PE women and normotensive pregnant women. BDNF correlated negatively with annexin A1, and positively with body mass index and diastolic blood pressure. No correlation was significant in normotensive pregnant women. ConclusionsLower BDNF plasma concentrations and cross-talk between BDNF and AnxA1 signaling pathways might be involved in PE pathogenesis.

Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis

The aim of this study was to evaluate neuroendocrine activation during stress in patients with recently diagnosed multiple sclerosis before starting the immunomodulatory therapy (EDSS score≤2.0). We verified the hypothesis that certain cognitive and affective dysfunction is present already at this early stage of the disease. The sample consisted of 38 subjects, which involved patients who were recently diagnosed multiple sclerosis and age- and sex-matched healthy volunteers. Stroop test served as mental stress model enabling measurement of cognitive performance. Present results showed increased state anxiety, depression scores and poorer performance in the Stroop test in the group of patients compared to healthy subjects. The cognitive dysfunction was particularly evident in male patients with simultaneously decreased concentrations of the brain-derived neurotrophic factor (BDNF) in plasma. The patients at this stage of the disease have not yet developed the hyperactivity of the hypothalamic-pituitary-adrenocortical axis. They showed normal levels of plasma copeptin and reduced aldosterone response to mental stress test in women only. Concentrations of plasma copeptin were higher in men compared to women. Very early stages of multiple sclerosis are accompanied by disturbances in psychological well-being, mild cognitive dysfunction and decreased plasma concentrations of BDNF, particularly in male patients.

Effect of Intensive Training on Mood With No Effect on Brain-Derived Neurotrophic Factor.

Monitoring mood state is a useful tool for avoiding nonfunctional overreaching. Brain-derived neurotrophic factor (BDNF) is implicated in stress-related mood disorders. To investigate the impact of intensified training-induced mood disturbance on plasma BDNF concentrations at rest and in response to exercise. Eight cyclists performed 1 wk of normal (NT), 1 wk of intensified (INT), and 1 wk of recovery (REC) training. Fasted blood samples were collected before and after exercise on day 7 of each training week and analyzed for plasma BDNF and cortisol concentrations. A 24-item Profile of Mood State questionnaire was administered on day 7 of each training week, and global mood score (GMS) was calculated. Time-trial performance was impaired during INT (P = .01) and REC (P = .02) compared with NT. Basal plasma cortisol (NT = 153 ± 16 ng/mL, INT = 130 ± 11 ng/mL, REC = 150 ± 14 ng/ml) and BDNF (NT = 484 ± 122 pg/mL, INT = 488 ± 122 pg/mL, REC = 383 ± 56 pg/mL) concentrations were similar between training conditions. Likewise, similar exercise-induced increases in cortisol and BDNF concentrations were observed between training conditions. GMS was 32% greater during INT vs NT (P < .001). Consistent with a state of functional overreaching (FOR), impairments in performance and mood state with INT were restored after 1 wk of REC. These results support evidence for mood changes before plasma BDNF concentrations as a biochemical marker of FOR and that cortisol is not a useful marker for predicting FOR.

A prospective, longitudinal study of platelet serotonin and plasma brain-derived neurotrophic factor concentrations in major depression: effects of vortioxetine treatment.

Various antidepressants occupy brain serotonin transporter (SERT), decrease platelet serotonin (5-HT) concentration, and normalize reduced plasma brain-derived neurotrophic factor (BDNF) concentrations in depressed patients. Vortioxetine is a recently introduced antidepressant with a multimodal mechanism of action. In addition to SERT inhibition, vortioxetine acts via different 5-HT receptors. To further elucidate its mechanism of action, we have investigated the effects of vortioxetine on platelet 5-HT and plasma BDNF concentrations in patients with major depression. Platelet 5-HT and plasma BDNF concentrations were determined in 44 healthy subjects at baseline and in 44 depressed patients before and after 4weeks of treatment with vortioxetine (5-15mg daily). Platelet 5-HT concentration was determined using the ortho-phthalaldehyde-enhanced fluorometric method, and plasma BDNF concentration using a commercial enzyme-linked immunosorbent assay (Quantikine ELISA, R&D Systems). At baseline, platelet 5-HT concentrations did not differ between depressed and control subjects, but plasma BDNF values were lower (p = 0.011; ω = 0.80) in depressed patients than in healthy subjects. Vortioxetine treatment significantly (p < 0.0001; ω = 0.80) decreased platelet 5-HT concentration and significantly (p = 0.004; ω = 0.80) increased plasma BDNF concentration in depressed patients compared to their baseline values. Age, gender, and smoking were not significantly associated with platelet 5-HT and plasma BDNF concentrations. Despite a novel mechanism of action, vortioxetine shares some common effects with other antidepressants. This study is the first to show that, in addition to clinical improvement, 4weeks of treatment with vortioxetine (5-15mg daily), decreased platelet 5-HT and increased plasma BDNF concentrations in depressed patients.

The relationship between brain-derived neurotrophic factor, irisin and cognitive skills of endurance athletes

ABSTRACTObjective: The objective of this study was to assess the cognitive performance of endurance athletes and its relation with circulating brain-derived neurotrophic factor (BDNF) and irisin levels.Methods: 26 endurance athletes (14 elite orienteers (mean ± SD: age = 26.33 ± 4.08, body weight = 70.33 ± 4.64, body height = 177.7 ± 6.1), 12 pentathletes (mean ± SD: age = 29.42 ± 5.32, body weight = 74.77 ± 6.59, body height = 180.8 ± 3.8)) and ten sedentary (mean ± SD: age = 27.30 ± 2.06, body weight = 76.65 ± 12.50, body height = 176.9 ± 5.2) men at almost same ages and educational levels participated in this study. Cognitive functions were analyzed with mini-mental-state examination (MMSE) and Isaacs’ Set Test of Verbal Fluency (IST) tests. Insulin-like growth factor-1 (IGF-1), BDNF and irisin levels were measured in the blood samples.Results: The MSSE and IST scores of the endurance athletes were higher than that of the sedentary control group (P < 0.05). Serum IGF-1 levels were higher in the pentathletes (111.18 ± 22.26 ng mL−1) than the orienteers (85.89 ± 19.32 ng mL−1) (P < 0.05). Plasma BDNF (2.78 ± 0.81, 4.28 ± 1.03, and 3.93 ± 0.77 ng mL−1 in the sedentary, orienteers and pentathletes, respectively) and irisin (3.25 ± 0.70, 6.16 ± 0.99, and 6.58 ± 1.09 µg mL−1 in the sedentary, orienteers and pentathletes, respectively) concentrations of the endurance trained athletes were higher than that of the sedentary control group (P < 0.05). Positive correlation between the cognitive function test results and BDNF and irisin concentrations were observed (P < 0.05). There was also a positive correlation between the circulating irisin and BDNF concentrations (P < 0.05).Conclusion: These results suggested that irisin and BDNF levels positively correlated with cognition in the endurance trained athletes.

BDNF Concentrations Are Elevated During Acute Resistance Exercise In Experienced, Resistance-trained Men

Background: Brain-derived neurotrophic factor (BDNF) has been demonstrated to have an important role in neuronal remodeling and modulating synaptic plasticity and neurotransmitter release. Acute elevations in BDNF concentrations have been seen during exercise, the understanding in resistance trained (RT) men, and the difference between high intensity (HI) and high volume (HV) protocols is limited. PURPOSE: To examine the response of BDNF to acute bouts of HI and HV in experienced, RT men. METHODS: Twenty experienced resistance trained men (23.5 ± 2.6 y, 1.79 ± 0.05 m, 75.7 ± 13.75) volunteered for this study. To ensure participants were trained, 10 weeks of supervised training occurred prior to the acute bout. The first 2-weeks was a preparatory phase, after which participants were randomized into either a HV (n = 10, 4 x 10-12RM, 1-min rest) or HI (n = 10, 4 x 3-5RM, 3-min rest) training protocol. Participants trained for an additional 8 weeks (4 d·week-1). During the acute training session resting blood draws were obtained prior to (PRE), immediately (IP), 30 min (30P), and 60 min (60P) post-exercise. Plasma BDNF concentrations were determined using a multiplex signaling assay kit and analyzed with MAGPIX® technology. Data were analyzed using a group x time repeated measures ANOVA. Additionally, area under curve (AUC) was calculated and analyzed with an independent t-test. RESULTS: The repeated measures ANOVA demonstrated a significant (p=0.019) main effect for time. BDNF concentrations were significantly elevated from PRE (1911.63 ± 447.79 pg·ml-1) at 30P (3579.47 ± 680.04 pg·ml-1), and 60P (3307.75 ± 536.80 pg·ml-1). In addition, BDNF concentrations were significantly greater at 30P than IP (2624.37 ± 399.67 pg·ml-1). When collapsed across time, the BDNF response during HV (3572.92 ± 545.33 pg·ml-1) tended to be higher (p = 0.079) than during HI (2138.69 ± 545.33 pg·ml-1). However, no significant interactions (p=0.325), or differences for AUC (p=0.257) were observed. CONCLUSIONS: The results of this study indicate BDNF increases in response to a resistance training stress in resistance trained men. However, comparisons between HV and HI training indicates a trend towards a difference in the BDNF response.

Plasma Brain-Derived Neurotrophic Factor as a Biomarker for the Main Types of Mild Neurocognitive Disorders and Treatment Efficacy: A Preliminary Study.

Decreased levels of brain-derived neurotrophic factor (BDNF) are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs). In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram) in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer's disease (MNCD-AD); 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD) according to Frisoni et al. (2002) and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94%) to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy.

Neither cortisol nor brain-derived neurotrophic factor is associated with serotonin transporter in bipolar disorder

Converging evidence indicates the hypothalamus–pituitary–adrenal axis and serotonergic neurons exert reciprocal modulatory actions. Likewise, brain-derived neurotrophic factor (BDNF) has been implicated as a growth and differentiation factor in the development of serotonergic neurons. The aim of this study was to examine the interaction of cortisol and BDNF on serotonin transporter (SERT) in bipolar disorder (BD). Twenty-eight BD and 28 age- and gender-matched healthy controls (HCs) were recruited. 123I-ADAM with single-photon emission computed tomography (SPECT) was applied for measurement of SERT availability in the brain, which included the midbrain, thalamus, putamen and caudate. Ten milliliters of venous blood was withdrawn, when the subject underwent SPECT, for the measurement of the plasma concentration of cortisol and BDNF. SERT availability was significantly decreased in the midbrain and caudate of BD compared with HCs, whereas plasma concentration of cortisol and BDNF did not show a significant difference. The linear mixed-effect model revealed that there was a significant interaction of group and cortisol on SERT availability of the midbrain, but not BDNF. Linear regression analyses by groups revealed that cortisol was associated with SERT availability in the midbrain in the HCs, but not in BD. Considering previous studies, which showed a significant association of cortisol with SERT availability in the HCs and major depressive disorder (MDD), our result replicated a similar finding in HCs. However, the negative finding of the association of cortisol and SERT availability in BD, which was different from MDD, suggests a different role for cortisol in the pathophysiology of mood disorder.

Plasma brain-derived neurotrophic factor levels after severe traumatic brain injury

Objective: Severe traumatic brain injury (TBI) is associated with a 30–70% mortality rate. Nevertheless, in clinical practice there are no effective biomarkers for the prediction of fatal outcome following severe TBI. Therefore, the aim was to determine whether brain-derived neurotrophic factor (BDNF) plasma levels are associated with intensive care unit (ICU) mortality in patients with severe TBI.Methods: This prospective study enrolled 120 male patients who suffered severe TBI (Glasgow Coma Scale 3–8 at emergency room admission). The plasma BDNF level was determined at ICU admission (mean 6.4 hours after emergency room admission).Results: Severe TBI was associated with a 35% mortality rate and 64% of the patients presented severe TBI with multi-trauma. The mean plasma BDNF concentration among the severe TBI victims was 704.2 ± 63.4 pg ml−1 (±SEM). Nevertheless, there were no significant differences between BDNF levels in the survivor (700.2 ± 82.8 pg ml−1) or non-survivor (711.6 ± 97.4 pg ml−1) groups (p = 0.238) or in the isolated TBI (800.4 ± 117.4 pg ml−1) or TBI with multi-trauma groups (650.5 ± 73.9 pg ml−1) (p = 0.109).Conclusions: Plasma BDNF concentrations did not correlate with either short-term fatal outcome or type of injury following severe TBI.

Brain-derived neurotrophic factor correlates with functional and cognitive impairment in non-disabled older individuals

We used a complete battery of geriatric and psychometric tests to evaluate whether plasma-borne brain-derived neurotrophic factor (BDNF), a master molecule in neuroplasticity, is associated with the severity of functional and cognitive impairment in non-disabled older individuals. There was a significant positive correlation between BDNF plasma concentrations and the Barthel index, a measurement of the ability of individuals to perform the activities of daily living (p=0.03) and the concentration subcategory measured with the mini mental state examination (MMSE) test (p=0.01). Furthermore, plasma BDNF inversely and significantly correlated with the blood eosinophil count (p=0.01), the total cholesterol concentration (p=0.04), and high-density lipoprotein cholesterol (p=0.04). However, BDNF did not correlate with any other socio-demographic or clinical characteristics, other analytical parameters measured in the blood, or any other geriatric assessment scales. Our results suggest that BDNF may play a role in the pathophysiology of functional impairment in the elderly and in some aspects of cognitive function. However, more studies are needed to understand the relationship between circulating BDNF and functional impairment to determine if BDNF represents a candidate biomarker for this type of cognitive impairment.

Assessing brain-derived neurotrophic factor as a novel clinical marker of endometriosis

To evaluate novel clinical markers of endometriosis including the neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin 4/5 (NT4/5) and compare them to others previously reported in the literature including cancer antigen 125 (CA-125) and C-reactive protein (CRP). Prospective study. University hospital. One hundred thirty-eight women were prospectively and consecutively recruited (April 2011-April 2015; cases: undergoing endometriosis surgery, n = 96; controls: benign gynecological surgery, n = 24 combined with healthy women, no history of pelvic pain, not undergoing surgery, n = 18). Collection of peripheral blood, gynecological and demographic information, eutopic biopsy in women undergoing laparoscopy. Circulating BDNF, NGF, NT4/5, CA-125, and CRP were quantified by ELISA. Plasma concentrations of BDNF were significantly greater in women with endometriosis (1,091.9 pg/mL [640.4-1,683.1]; n = 68, untreated) than in controls (731.4 pg/mL [352.1-1,176.2]; n = 36), whereas circulating NGF, NT4/5, CA-125, and CRP were not different. When assessed for their ability to differentiate between women with revised Classification of the American Society of Reproductive Medicine stage 1 and 2 or stage 3 and 4 disease and controls, BDNF was the only putative marker able to identify stage 1 and 2 disease, with a sensitivity and specificity of 91.7% and 69.4%, respectively, using an arbitrary cutoff value of 1,000 pg/mL. We also demonstrated that circulating BDNF in women with endometriosis who were receiving ovarian suppression for disease was equivalent to that in the control group. This suggests that BDNF may also offer the opportunity to monitor patient response to treatment. Plasma BDNF is a potentially useful clinical marker of endometriosis that is superior to NGF, NT4/5, CA-125, and CRP.

Mechanisms linking depression co-morbid with obesity: An approach for serotonergic type 3 receptor antagonist as novel therapeutic intervention.

Despite of the enormous research, therapeutic treatment for depression has always been a serious issue. Even though depression and obesity are individual abnormal health conditions, each act as a triggering factor for the other. Obese individuals are twice prone to develop depression than that of non-obese persons. The exact mechanism how obesity increases the risk for depression still remains an area of interest for research in neuropsychopharmacology. Depression and obesity share some common pathological pathways such as hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis, dysregulation of oxidant/antioxidant system balance, higher level of inflammatory cytokines, leptin resistance, altered plasma glucose, insulin resistance, reduced neuronal brain derived neurotrophic factor (BDNF) and decreased serotonergic neurotransmission in various regions of brain. The antidepressant-like effect of 5-HT3 receptor antagonists through allosteric modulation of serotonergic pathways is well evident from several research investigations belonging to our and some in other laboratories. Furthermore, serotonin regulates diet intake, leptin, corticosterone, inflammatory mechanisms, altered plasma glucose, insulin resistance and BDNF concentration in brain. The present review deals with various biological mechanisms involved in depression co-morbid with obesity and 5-HT3 receptor antagonists by modulation of serotonergic system as a therapeutic target for such co-morbid disorder.

Prolonged hyperglycemia & hyperinsulinemia increases BDNF mRNA expression in the posterior ventromedial hypothalamus and the dorsomedial hypothalamus of fed female rats.

Brain-derived neurotrophic factor (BDNF) plays a key role in neuronal development, synaptic plasticity, and the central control of energy homeostasis. Peripheral metabolic signals such as leptin and glucose regulate hypothalamic BDNF gene expression. However, the effects of long-term hyperglycemia and/or hyperinsulinemia on BDNF mRNA levels in the hypothalamus and other brain regions where BDNF regulates physiological functions have not been investigated. Therefore, using in situ hybridization we examined whether high glucose, high insulin, or both affected BDNF gene expression in vivo. Ovariectomized, estrogen-replaced adult rats were fitted with indwelling jugular catheters and infused for 48 h with: saline (control), glucose (hyperglycemia-hyperinsulinemia), glucose with insulin (hyperinsulinemia only), diazoxide (Dzx) (control), or glucose with Dzx (hyperglycemia only). Glucose infusion (Hyperglycemia and hyperinsulinemia) significantly increased BDNF mRNA expression in the posterior ventromedial nucleus of the hypothalamus (pVMH) and in the dorsomedial nucleus of the hypothalamus (DMH). Unexpectedly, infusion of the KATP channel opener Dzx also increased BDNF mRNA expression in the pVMH and DMH. In contrast, no significant changes in BDNF mRNA expression were observed in the groups that were hyperinsulinemic only or hyperglycemic only. BDNF mRNA expression did not differ as a function of treatment in the anterior VMH, paraventricular nucleus of the hypothalamus, the hippocampus, or the amygdala. Hyperglycemia with and without hyperinsulinemia decreased BDNF mRNA levels in the pituitary. Plasma BDNF concentrations were not changed by any of the treatments. Our results suggest that hyperinsulinemia alone does not affect BDNF mRNA expression in the hypothalamus, hippocampus, or pituitary. Our study is the first to distinguish that within the hypothalamus, prolonged high glucose levels in non-fasted rats regulates BDNF gene expression in a brain nuclei-specific fashion.

Brain-derived neurotrophic factor and substrate utilization following acute aerobic exercise in obese individuals.

Brain-derived neurotrophic factor (BDNF) serves as a vital regulator of neuronal proliferation and survival, and has been shown to regulate energy homeostasis, glucose metabolism and body weight maintenance. Elevated concentrations of plasma BDNF have been associated with obesity and type 2 diabetes mellitus. Acute aerobic exercise transiently increases circulating BDNF, potentially correcting obesity-related metabolic impairment. The present study aimed to compare acute aerobic exercise elicited BDNF responses in obese and normal-weight subjects. Furthermore, we aimed to investigate whether acute exercise-induced plasma BDNF elevations would be associated with improved indices of insulin resistance, as well as substrate utilization [carbohydrate oxidation (CHOoxi) and fat oxidation (FAToxi)]. Twenty-two healthy, untrained subjects [11 obese (four men and seven women; age = 22.91 ± 4.44 years; body mass index = 35.72 ± 4.17 kg/m(2)) and 11 normal-weight (five men and six women; age = 23.27 ± 2.24 years; body mass index = 21.89 ± 1.63 kg/m(2))] performed 30 min of continuous submaximal aerobic exercise at 75% maximal oxygen consumption. Our analyses showed that the BDNF response to acute aerobic exercise was similar in obese and normal-weight subjects across time (time: P = 0.015; group: P = not significant) and was not associated with indices of IR. Although no differences in the rates of CHOoxi and FAToxi were found between both groups, total relative energy expenditure was significantly lower in obese subjects compared to normal-weight subjects (3.53 ± 0.25 versus 5.59 ± 0.85; P < 0.001). These findings suggest that acute exercise-elicited BDNF elevation may not be sufficient to modulate indices of IR or the utilization of either carbohydrates or fats in obese individuals.

Diurnal Variation of Plasma Brain-Derived Neurotrophic Factor Levels in Women with Functional Hypothalamic Amenorrhea

Background: Brain-derived neurotrophic factor (BDNF) is strongly related to hormonal networks and is modulated by hypothalamic activity. Objective: To evaluate plasma BDNF concentration in patients with functional hypothalamic amenorrhea (FHA), with reference to the BDNF circadian rhythm and its relation with the cortisol (F) rhythm, and to assess whether the duration of amenorrhea might influence the BDNF:F ratio in FHA. Design: This was an observational study evaluating 36 amenorrheic and 30 eumenorrheic women. Setting: Basal values of BDNF and hormones were examined in blood samples collected from 7:00 to 9:00 h in all the women. Basal BDNF and F levels were determined in blood samples collected in 12 subjects from each group at 8:00, 12:00, 16:00, 20:00, and 24:00 h. Results: BDNF plasma levels are significantly lower in amenorrheic women (p < 0.001) than in the follicular phase of eumenorrheic women. There are no correlations between BDNF values (p > 0.05), sex steroids, and F in FHA. Low plasma BDNF levels in FHA are not significantly correlated with duration of amenorrhea. The 24-hour variation of BDNF in amenorrheic women is significantly lower when compared to the control group, and normal daily variations of BDNF disappeared in FHA patients. F preserved its circadian rhythm in both groups. Conclusions: Interactions between BDNF, the hypothalamus-pituitary-adrenal axis, and sex steroids might be critical in clinical conditions of modified homeostasis/adaptation, such as FHA.

Plasma concentrations of BDNF and IGF-1 in abstinent cocaine users with high prevalence of substance use disorders: relationship to psychiatric comorbidity.

Recent studies have identified biomarkers related to the severity and pathogenesis of cocaine addiction and common comorbid psychiatric disorders. Monitoring these plasma mediators may improve the stratification of cocaine users seeking treatment. Because the neurotrophic factors are involved in neural plasticity, neurogenesis and neuronal survival, we have determined plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1) and IGF-1 binding protein 3 (IGFBP-3) in a cross-sectional study with abstinent cocaine users who sought outpatient treatment for cocaine (n = 100) and age/body mass matched controls (n = 85). Participants were assessed with the diagnostic interview ‘Psychiatric Research Interview for Substance and Mental Disorders’. Plasma concentrations of these peptides were not different in cocaine users and controls. They were not associated with length of abstinence, duration of cocaine use or cocaine symptom severity. The pathological use of cocaine did not influence the association of IGF-1 with age observed in healthy subjects, but the correlation between IGF-1 and IGFBP-3 was not significantly detected. Correlation analyses were performed between these peptides and other molecules sensitive to addiction: BDNF concentrations were not associated with inflammatory mediators, lipid derivatives or IGF-1 in cocaine users, but correlated with chemokines (fractalkine/CX3CL1 and SDF-1/CXCL12) and N-acyl-ethanolamines (N-palmitoyl-, N-oleoyl-, N-arachidonoyl-, N-linoleoyl- and N-dihomo-γ-linolenoyl-ethanolamine) in controls; IGF-1 concentrations only showed association with IGFBP-3 concentrations in controls; and IGFBP-3 was only correlated with N-stearoyl-ethanolamine concentrations in cocaine users. Multiple substance use disorders and life-time comorbid psychopathologies were common in abstinent cocaine users. Interestingly, plasma BDNF concentrations were exclusively found to be decreased in users diagnosed with both primary and cocaine-induced disorders for mood and anxiety disorders. In summary, BDNF, IGF-1 and IGFBP-3 were not affected by a history of pathological use of cocaine supported by the absence of associations with other molecules sensitive to cocaine addiction. However, BDNF was affected by comorbid mood disorders. Further research is necessary to elucidate the role of BDNF and IGF-1 in the transition to cocaine addiction and associated psychiatric comorbidity.

Insulin resistance and brain-derived neurotrophic factor levels in chronic kidney disease

Insulin resistance is a frequent abnormality in chronic kidney disease (CKD) appearing in early stages. Factors known to promote insulin resistance in CKD patients include disorders of ion and acid-base equilibrium and circulating uremia toxins. Recent research has focused on the central nervous system as the source of the brain-derived neurotrophic factor (BDNF). The aim of our work was to study plasma BDNF concentrations in stage 3 and 4 CKD patients in relationship with insulin resistance and distribution of adipose tissue. Plasma BDNF concentrations were measured in a study group of 31 patients, including a subgroup of 20 non-diabetic subjects. Additionally dual-energy X-ray absorptiometry (DXA) was performed. Homeostatic model assessment of insulin resistance (HOMA-IR) and homeostatic model assessment of B-cell function (HOMA-beta) indices were calculated. Two separate analyses were performed. In the first analysis performed in all 31 CKD patients, there were no correlations between BDNF and: body mass index (BMI), android, gynoid fat distribution, HOMA-IR and HOMA-beta. In the second analysis performed in 20 CKD patients without diabetes, BDNF was negatively related to gynoid fat (Rs = -0.47, P = 0.034) and women revealed significantly lower levels of BDNF than men (P = 0.046). Normotensive patients disclosed significantly higher BDNF levels than hypertensive patients in the whole CKD group (P = 0.039) and in the non-diabetic subgroup (P = 0.028). No correlations between BDNF and eGFR were found. Female sex and arterial hypertension are associated with lower BDNF plasma concentration in CKD patients.