Increased Plasma Brain-derived Neurotrophic Factor Research Articles

An Examination into the Effects of a Nutraceutical Supplement on Cognition, Stress, Eye Health, and Skin Satisfaction in Adults with Self-Reported Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory (p = 0.037), but not for working memory (p = 0.418) or verbal learning (p = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire (p = 0.022), increased plasma brain-derived neurotrophic factor (p = 0.030), decreased plasma malondialdehyde (p = 0.040), and increased skin carotenoid concentrations (p = 0.006). However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.

Pimavanserin treatment increases plasma brain-derived neurotrophic factor levels in rats.

Pimavanserin, a serotonin 5HT-2A receptor inverse agonist is the first-line, FDA-approved treatment of hallucinations and delusions associated with Parkinson's Disease psychosis (PDP), which occurs in up to 50% of PD patients. The neurobiological mechanism underlying the therapeutic effectiveness of Pimavanserin in PDP remains unknown. Several earlier studies have shown that treatment with 5HT-2A antagonists and other drugs acting on the serotonergic system such as SSRIs increase Brain derived neurotrophic factor (BDNF) levels in rodents. BDNF is synthesized as the precursor proBDNF, that undergoes cleavage intra or extracellularly to produce a mature BDNF (mBDNF) protein. mBDNF is believed to play a key role in neuroplasticity and neurogenesis. The present study tested the hypothesis that treatment with Pimavanserin is associated with higher and sustained elevations of mBDNF. Adult Sprague-Dawley male rats were treated with Pimavanserin, Fluoxetine or vehicle for 4 weeks (chronic) or 2 h (acute). BDNF levels were determined by enzyme-linked Immunosorbent assay (ELISA). We found significant increases in plasma mBDNF levels in rats following chronic Pimavanserin treatment, but not in Fluoxetine-treated rats. No significant changes in mBDNF levels were found in the prefrontal cortex or hippocampus following Pimavanserin or Fluoxetine treatment. These findings suggest that increase in mBDNF levels could be a contributing mechanism for the neuroprotective potential of Pimavanserin.

Abstract TMP118: Brain Derived Neurotrophic Factor Secretion From Lungs Mediate The Post-stroke Functional Recovery After Systemic Administration Of MSCs

Background: Bone marrow derived mesenchymal stromal cells (MSCs) have been actively tested in clinical trials. After intravenous (IV) administration, vast majority of them are trapped in lung vasculature, with only few reaching brain. Even though MSCs are short-lived in the lungs, their beneficial effects on post-stroke recovery extends for weeks, suggesting a paracrine mechanism of action. Integrins expression on MSCs is known to mediate the lung entrapment by binding to ICAM1-expressing endothelial cells (ECs). Furthermore, ECs can perform paracrine functions by releasing neurotrophins, such as brain derived neurotrophic factor (BDNF). We explored EC-MSC interaction in lungs, and its effect on BDNF release from lung ECs, in an experimental stroke model. Methods: Human lung ECs (Cell Biologics) were cultured at P3. Human MSCs were isolated from bone marrow of healthy donor and P3 MSCs were used for experiments. Serum from stroke patients with NIH Stroke Scale (NIHSS) severity ranging from 0 to 10 was collected at 24 hours after stroke. Co-culture experiments were done in trans-well plates. BDNF mRNA was isolated using Qiagen RNeasy kit. Middle Cerebral Artery Occlusion model (filament model) was used in C57BL/6 mice. Modified Neurological Severity Score (mNSS) was used for functional assessment in mice stroke model. Results: Human primary lung ECs exposed to plasma from stroke patients as well as recombinant TNF-α showed robust increase in BDNF secretion, with MSCs enhancing the secretion furthermore. BDNF mRNA was robustly increased in whole mouse lungs as well as lung ECs. IV MSC administration robustly increased plasma BDNF and BDNF mRNA expression in mouse lung ECs. Furthermore, IV MSCs provided better functional recovery as compared to IV BDNF. Conclusion: BDNF is already known to be neuroprotective. Our results show that BDNF secretions increase from lung ECs after IV MSC administration, which could mediate functional recovery in mice after stroke.

Increased plasma brain-derived neurotrophic factor (BDNF) as a potential biomarker for and compensatory mechanism in mild cognitive impairment: a case-control study.

Background: Previous meta-analyses examining the continuum of Alzheimer’s disease (AD) concluded significantly decreased peripheral brain-derived neurotrophic factor (BDNF) in AD. However, across different meta-analyses, there remain inconsistent findings on peripheral BDNF levels in individuals with mild cognitive impairment (MCI). This issue has been attributed to the highly heterogenous clinical and laboratory factors. Thus, BDNF’s level, discriminative accuracy for identifying all-cause MCI and its subtypes, and its associations with other biomarkers and neurocognitive domains, remain largely unknown.Methods: To address this heterogeneity, we compared a healthy control cohort (n=56, 45 female) to an MCI cohort (n=40, 28 female), to determine whether plasma BDNF, hs-CRP, and DHEA-S can differentiate healthy from MCI individuals, including two MCI subtypes (amnestic [aMCI] and non-amnestic [non-aMCI]). The associations between BDNF with other biomarkers and neurocognitive tests were examined. Adults with cerebral palsy were included as sensitivity analyses.Results: Compared to healthy controls, BDNF was significantly higher in all-cause MCI, aMCI, and non-aMCI. Furthermore, BDNF had good (AUC=0.84, 95% CI=0.74 to 0.95, p<0.001) and excellent discriminative accuracies (AUC=0.92, 95% CI=0.84 to 1.00, p<0.001) for all-cause MCI and non-amnestic MCI, respectively. BDNF was significantly and positively associated with plasma hs-CRP (β=0.26, 95% CI=0.02 to 0.50, p=0.038), despite attenuated association upon controlling for BMI (β=0.15, 95% CI=-0.08 to 0.38, p=0.186). Multiple inverse associations between BDNF and detailed neurocognitive tests were also detected.Conclusions: These findings suggest BDNF is increased as a compensatory mechanism in preclinical dementia, supporting the neurotrophic and partially the inflammatory hypotheses of cognitive impairment.

Dual Profile of Environmental Enrichment and Autistic-Like Behaviors in the Maternal Separated Model in Rats.

Background: Environmental Enrichment (EE) has been suggested as a possible therapeutic intervention for neurodevelopmental disorders such as autism. Although the benefits of this therapeutic method have been reported in some animal models and human studies, the unknown pathophysiology of autism as well as number of conflicting results, urge for further examination of the therapeutic potential of EE in autism. Therefore, the aim of this study was to examine the effects of environmental enrichment on autism-related behaviors which were induced in the maternal separation (MS) animal model. Material and Methods: Maternally separated (post-natal day (PND) 1–14, 3 h/day) and control male rats were at weaning (PND21) age equally divided into rats housed in enriched environment and normal environment. At adolescence (PND42–50), the four groups were behaviorally tested for direct social interaction, sociability, repetitive behaviors, anxiety behavior, and locomotion. Following completion of the behavioral tests, the blood and brain tissue samples were harvested in order to assess plasma level of brain derived neurotrophic factor (BDNF) and structural plasticity of brain using ELISA and stereological methods respectively. Results: We found that environmental enrichment reduced repetitive behaviors but failed to improve the impaired sociability and anxiety behaviors which were induced by maternal separation. Indeed, EE exacerbated anxiety and social behaviors deficits in association with increased plasma BDNF level, larger volume of the hippocampus and infra-limbic region and higher number of neurons in the infra-limbic area (p < 0.05). Conclusion: We conclude that environmental enrichment has a significant improvement effect on the repetitive behavior as one of the core autistic-like behaviors induced by maternal separation but has negative effect on the anxiety and social behaviors which might have been modulated by BDNF.

Hypertriglyceridemia-induced brain-derived neurotrophic factor in rat submandibular glands

ObjectivesSalivary glands produce brain-derived neurotrophic factor (BDNF), which increases plasma BDNF content. Salivary BDNF influences the hippocampus and enhances anxiety-like behaviors. Dyslipidemia affects the brain, promoting depression and anxiety-like behaviors. This study was performed to investigate whether hypertriglyceridemia influences salivary BDNF expression. MethodsHypertriglyceridemia was induced in rats by high-fat diet intake for 10 weeks. BDNF protein levels in the saliva and submandibular glands were measured using enzyme-linked immunosorbent assay (ELISA). Bdnf mRNA levels in the submandibular gland were determined using real-time polymerase chain reaction. ResultsA hypertriglyceridemia rat model was established. Body weight did not differ between the control and hypertriglyceridemia groups. Bdnf mRNA and protein expression was increased in the submandibular gland in the hypertriglyceridemia group compared to the control group. BDNF expression was also significantly increased in the saliva of the hypertriglyceridemia group. ConclusionsThis is first study to show that hypertriglyceridemia induces BDNF expression in the rat submandibular gland and suggests that salivary BDNF is associated with lipid metabolism.

Effect of vortioxetine vs. escitalopram on plasma BDNF and platelet serotonin in depressed patients

Escitalopram and vortioxetine are efficacious antidepressants. They directly target serotonin (5-HT) system, but vortioxetine mechanism of action is distinct from the one of selective serotonin reuptake inhibitors (SSRIs). Treatment with SSRIs decrease platelet 5-HT concentration and increase peripheral brain-derived neurotrophic factor (BDNF) levels. Since vortioxetine has a multimodal mechanism of action, it is expected to have a greater effect on circulatory BDNF concentration, compared to conventional antidepressants. This longitudinal study aimed to explore and compare the effects of 4-weeks of treatment with vortioxetine and escitalopram on plasma BDNF and platelet 5-HT concentration in patients with major depressive disorder (MDD). The results revealed that vortioxetine significantly increased plasma BDNF concentration (p = .018) and significantly decreased platelet 5-HT concentration (p < .001). Treatment with escitalopram significantly decreased platelet 5-HT concentration (p < .001), but it did not affect plasma BDNF concentration (p = .379). Response to vortioxetine was not predicted by baseline plasma BDNF or platelet 5-HT concentration, but response to escitalopram was predicted by baseline platelet 5-HT concentration. These effects might be due to vortioxetine unique mechanism of action, but the clinical implications are unclear. It remains to be determined whether this finding extends during long-term vortioxetine treatment, and which, if any, clinical effects emerge from BDNF increase.

Effects of exercise on BDNF-TrkB signaling in the paraventricular nucleus and rostral ventrolateral medulla in rats post myocardial infarction

Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling in the paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) is associated with cardiovascular regulation. Exercise increases plasma BDNF and attenuates activation of central pathways in the PVN and RVLM post myocardial infarction (MI). The present study assessed whether MI alters BDNF-TrkB signaling and intracellular factors Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Akt in the PVN and RVLM of male Wistar rats with or without exercise or treatment with the TrkB blocker ANA-12. A 4-week period of treadmill exercise training was performed in MI rats. A separate experiment was conducted with 2.5 mg/kg ANA-12 in sedentary MI rats. At 5 weeks post MI, in both the PVN and RVLM, the ratio of full-length TrkB (TrkB.FL) and truncated TrkB (TrkB.T1) was decreased. 0.5 mg/kg ANA-12 did not affect BDNF-TrkB signaling and cardiac function post MI, but 2.5 mg/kg ANA-12 further decreased ejection fraction (EF). Exercise increased mature BDNF (mBDNF) and decreased Akt activity in the PVN, whereas in the RVLM, exercise did not affect mBDNF but lowered p-CaMKIIβ. ANA-12 prevented the exercise-induced increase in mBDNF in the PVN and decrease in p-CaMKIIβ in the RVLM. In conclusion, exercise decreases Akt activity in the PVN and decreases p-CaMKIIβ in the RVLM post MI. BDNF-TrkB signaling only mediates the decrease in p-CaMKIIβ in the RVLM. The exercise-induced decreases in Akt activity in the PVN and p-CaMKIIβ in the RVLM may contribute to the attenuation of the decrease in EF and sympathetic hyperactivity post MI.

Increased plasma Brain-Derived Neurotrophic Factor (BDNF) levels in females with schizophrenia

Brain-Derived Neurotrophic Factor (BDNF) acts as a critical regulator of synaptogenesis and synaptic plasticity. Sex differences have been demonstrated in many aspects of schizophrenia. This study tested for sex-specific differences in peripheral BDNF levels in people with schizophrenia and healthy controls. We measured circulating plasma BDNF levels in 95 people with schizophrenia and 80 healthy controls. Plasma BDNF levels were significantly elevated in females with schizophrenia compared to males with schizophrenia and to female healthy controls. These results suggest that sex differences in peripheral BDNF levels may contribute to other sex related differences in schizophrenia.

Efficiency of long-term vinpocetine administration in the treatment of dizziness and associated statodynamic disorders in patients with chronic cerebrovascular insufficiency (EDELWEISS study)

Complaints of dizziness are common in patients diagnosed with chronic cerebrovascular insufficiency (CCVI). Effective therapy of these patients is one of the most urgent problems of outpatient neurological practice. Objective: to evaluate the efficiency and safety of long-term administration of vinpocetine (Cavinton Comforte) in the treatment of dizziness in patients with CCVI. Patients and methods . A total of 139 patients took part in an open-label parallel-group clinical study. Vinpocetine (Cavinton Comforte) and vestibular exercises were prescribed in Group 1 (n=69); vestibular exercises were used in Group 2 (n=70). The efficiency of treatment was evaluated using a visual analog scale (VAS) in assessing vertigo and dizziness, the Dizziness Handicap Inventory (DHI), the Drug Attitude Inventory (DAI), the Montreal Cognitive Assessment (MoCA), the 5-point Likert scale, and videonystagmographic tests. Plasma brain-derived neurotrophic factor (BDNF) concentrations were analyzed before and after treatment. The total duration of the investigation was 8 months (6 months of therapy and 2 months of follow-up after therapy discontinuation). Results and discussion . The administration of vinpocetine significantly decreased the subjective intensity of vertigo and dizziness (on the VAS) and improved daily activities in patients (on the DHI) and a number of parameters according to the video nystagmographic tests: pursuit and saccadic eye movement tests. According to the DNI scores, the improvement changes in the patients' condition significantly correlated with increased plasma BDNF expression throughout the follow-up (Pearson's correlation coefficient>0.5). The use of vinpocetine could improve cognitive functions (on the MoCA and the 5-point Likert scale) and increase patient adherence to the therapy performed (on the DAI). The clinically significant effect in improving the statodynamic function was shown by vinpocetine at 2 months of its administration and was highest at 5 months; there was a significant improvement in cognitive function at 6 months. The long-term use of vinpocetine was not associated with the risk of serious adverse events. Conclusion . The findings allow vinpocetine to be recommended for long-term (at least 5 months) treatment of vertigo, dizziness, and cognitive impairment in patients with CCVI, in this case, the clinical effect is achieved through stimulating neuroplasticity, inducing BDNF synthesis in particular.

Brain-derived neurotrophic factor: Biopsychosocial correlates and exercise response in mild traumatic brain injury

Recovery from mild traumatic brain injury (mTBI) is a dynamic, complex process, and pre-clinical research highlights brain-derived neurotrophic factor (BDNF) as an important mediator in functional and pathophysiologic outcomes. Although BDNF appears to also be a significant factor in recovery in humans, its role is less understood. Our purpose was (1) to examine the association of serum and platelet-poor plasma concentrations of BDNF to relevant biopsychosocial outcomes of mTBI recovery (i.e., neurocognitive performance [attention, processing speed, memory, executive functioning], sleep, balance, mood, and self-reported symptoms) and (2) to assess BDNF response to a single-session of aerobic exercise (40 minutes of stationary cycling at 65%–75% maximum heart rate). There were 36 participants (ages 18–40; 19 male, 17 female) in 2 groups: (1) mTBI participants (n = 26) who were 14–25 days post-injury were randomized to either aerobic or non-aerobic exercise (low intensity stretching) and (2) demographically-matched, non-injured participants (n = 10) who participated in a single session of aerobic exercise. Results indicate that serum BDNF concentration has significant ( p = 0.05), inverse relationships with both sleep dysfunction and state levels of anxiety. No significant association between exercise type and serum BDNF was found, but there was a small to medium effect size (= 0.08) for increased plasma BDNF after aerobic exercise in mTBI vs non-injured participants. Overall, peripheral BDNF concentrations are poorly correlated, which suggests they reflect different tissue sources. Serum BDNF was more sensitive to select biopsychosocial outcomes, particularly sleep quality and anxiety, regardless of injury status. Additionally, aerobic exercise may play a role in enhancing platelet-poor plasma BDNF response in the post-acute period after mTBI.

Increased Plasma Brain-Derived Neurotrophic Factor 10.5 h after Intake of Whole Grain Rye-Based Products in Healthy Subjects.

It has previously been shown in short-term interventions that kernel-based whole grain (WG) rye products have beneficial effects on test markers related to obesity and type 2 diabetes (T2D). T2D increases the risk of several severe health issues, including declined cognitive functions. The protein brain-derived neurotrophic factor (BDNF) is suggested to be a potential biomarker for neuronal integrity. The aim of this study was to investigate the effect on plasma BDNF concentrations, 10.5 h after the intake of WG rye. Healthy young adults were provided late evening meals consisting of WG rye kernel-based bread (RKB) or a white wheat flour-based bread (reference product (WWB)), in a randomized cross-over design. The BDNF concentrations were investigated at fasting in the morning 10.5 h after single evening meals with RKB and WWB, and also after three consecutive evening meals with RKB and WWB, respectively. No difference was observed in the BDNF concentrations depending on the priming setting (p > 0.05). The RKB evening meals increased the BDNF concentrations by 27% at fasting (p = 0.001), compared to WWB. The increase of BDNF after the RKB indicate that, in addition to anti-diabetic properties, the dietary fiber in WG rye may support neuronal integrity.

Response of brain-derived neurotrophic factor to combining cognitive and physical exercise

Purpose: Brain-derived neurotrophic factor (BDNF) is well known for its potential to promote brain plasticity. It has been proposed that combining cognitive and physical exercise (CCPE) may have the potential to generate more synergistic benefits in cognitive function than either cognitive exercise (CE) or physical exercise (PE) alone. The purpose of this study was to examine acute responses of peripheral BDNF levels and cognitive performance to CE, PE, and CCPE.Methods: Thirteen healthy adult men participated in four experimental sessions; a 30-min CE, a 30-min cycling PE at an intensity of 60% peak oxygen uptake, a 30-min CCPE at the same intensity as PE, and a 30-min session of complete rest. Plasma BDNF levels and cognitive performance were measured before and after each session.Results: Both PE and CCPE significantly increased plasma BDNF levels (p < .05). CE led to no significant increase (p ≥ .05), and there was no significant difference in peripheral BDNF levels between PE and CCPE (p ≥ .05). No session induced a significant change in cognitive performance (p ≥ .05).Conclusions: Our study suggests that CE and PE have different responses of peripheral BDNF levels and that CCPE had no additional or synergistic effect on peripheral BDNF levels compared with PE alone. This study offers further insights into the potential mechanisms underlying the respective roles of CE, PE, and CCPE for peripheral BDNF levels and cognitive performance.

Brain-derived neurotrophic factor as a biomarker for cognitive recovery in acute schizophrenia: 12-week results from a prospective longitudinal study

It is generally accepted that impaired cognitive function is a core feature of schizophrenia. There is evidence for the role of brain-derived neurotrophic factor (BDNF) in cognitive function. Olanzapine was reported to yield cognitive improvement in patients with schizophrenia. In this study, we performed a prospective, open-label, 12-week observation trial to investigate whether peripheral BDNF may represent a potential biomarker for the effect of cognitive improvement induced by olanzapine in patients with schizophrenia. In total, 95 patients with acute schizophrenia were enrolled in the study. We also recruited 72 healthy individuals for a control group. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate symptom severity and treatment response. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma BDNF levels were measured with an enzyme-linked immunosorbent assay. Of the 95 patients consented into the study, 68 completed the 12-week follow up. Our results showed that schizophrenia patients with acute exacerbation had significantly poorer performance than that of the controls (Ps < 0.01). A significantly decreased plasma level of BDNF in patients was observed compared with the controls (F = 7.77, P = 0.006). A significant improvement in each PANSS subscore and total score was observed when the patients completed this study (Ps < 0.01). Additionally, 12-week olanzapine treatment exhibited significant improvements in RBANS immediate memory, attention, and total scores (P = 0.018, 0.001, and 0.007, respectively). Along with the clinical improvement, plasma BDNF levels after 12-week olanzapine monotherapy (4.67 ± 1.74ng/ml) were also significantly increased compared with those at baseline (3.38 ± 2.11ng/ml) (P < 0.01). Spearman's correlation analysis showed that the increase in plasma levels of BDNF is significantly correlated with the change in the RBANS total scores (r = 0.28, P = 0.02) but not with the change in the PANSS total scores (r = - 0.18, P = 0.13). There is a significant correlation of BDNF increase with the change of RBANS attention subscore (r = 0.27, P = 0.028). Our findings suggest that olanzapine improves psychiatric symptoms and cognitive dysfunction, particularly attention and immediate memory, in patients with acute schizophrenia, in parallel with increased plasma BDNF levels. Plasma BDNF levels may be a potential biomarker for cognitive recovery in acute schizophrenia.

Chronic administration of ellagic acid improved the cognition in middle-aged overweight men

This study aimed to investigate if ellagic acid has beneficial effects on cognitive deficits in middle-aged overweight individuals and to propose a possible mechanism. A total of 150 middle-aged male participants, including 76 normal-weight and 74 overweight men, aged between 45 to 55 years, were recruited for this study. Both normal-weight and overweight participants were administered either 50 mg ellagic acid or placebo cellulose daily for 12 weeks. Blood lipids, peripheral brain-derived neurotrophic factor (BDNF), and saliva cortisol were assessed on the last day of the procedure to investigate the effects induced by ellagic acid. The results revealed that ellagic acid treatment improved the levels of blood lipid metabolism with a 4.7% decline in total cholesterol, 7.3% decline in triglycerides, 26.5% increase in high-density lipoprotein, and 6.5% decline in low-density lipoprotein. Additionally, ellagic acid increased plasma BDNF by 21.2% in the overweight group and showed no effects on normal-weight participants. Moreover, the increased saliva cortisol level in overweight individuals was inhibited by 22.7% in a 12-week ellagic acid treatment. Also, compared with placebo, overweight individuals who consumed ellagic acid showed enhanced cognitive function as measured by the Wechsler Adult Intelligence Scale-Revised and the Montreal Cognitive Assessment. To the best of our knowledge, this is the first report showing that ellagic acid prevents cognitive deficits through normalization of lipid metabolism, increase in plasma BDNF level, and reduction of saliva cortisol concentration. These results indicate that ellagic acid has a potential to restore cognitive performance related to mild age-related declines.

Elevated brain derived neurotrophic factor levels in plasma reflect in vivo functional viability of infused mesenchymal stem cells for stroke in rats.

Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow elicits functional recovery in rat stroke models and clinical studies in patients are ongoing. Brain derived neurotrophic factor (BDNF) is a neurotrophic factor produced by MSCs and may contribute to their therapeutic efficacy. The purpose of the current study was to determine if BDNF is elevated in infarcted brain and in which compartment of blood (plasma or serum) after intravenous MSC infusion in a middle cerebral artery occlusion (MCAO) model in the rat. In rats, a permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament and MSCs were intravenously administered 6 h after right MCAO induction. Enzyme-linked immunosorbent assay (ELISA) analysis of brain, serum and plasma BDNF were performed after the MSC infusion following the MCAO induction. Lesion volume was assessed using magnetic resonance imaging. Functional outcome was assessed using the Limb Placement Test. Infused MSCs reduced lesion volume and elicited functional improvement compared to the vehicle infused group. ELISA analysis of the MSC treated group revealed an increase BDNF levels in the infarcted hemisphere of the brain and plasma, but not in serum. The MSC group showed a greater increase in BDNF levels than sham control. In the MSC group, the expression of increased plasma BDNF levels correlated with increased brain BDNF levels. These results support the hypothesis that BDNF levels in plasma, but not serum, may be more appropriate to detect circulating BDNF in vivo following MSC infusion in a cerebral infarction rat model of ischemic stroke. Further, plasma BDNF might reflect in vivo functional viability of infused MSCs after stroke.

Tobacco use is associated with increased plasma BDNF levels in depressed patients.

Since serum Brain Derived Neurotrophic Factor (BDNF) levels are higher in tobacco smokers than in non-smokers and since Major Depressive Disorder (MDD) is associated with a 2-fold increased risk of smoking, we assessed the association of smoking and plasma BDNF levels in 359 depressed MDD patients. Plasma BDNF levels were positively correlated with the magnitude of tobacco consumption (current number of cigarettes/day and number of packs/year). Accordingly, current tobacco users had significantly higher plasma BDNF levels than non-users. In further studies of MDD, peripheral measures of BDNF should take into account tobacco use.

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.

Electroconvulsive therapy (ECT) and aerobic exercise training (AET) increased plasma BDNF and ameliorated depressive symptoms in patients suffering from major depressive disorder

BackgroundTo treat patients suffering from major depressive disorder (MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three-arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2. plasma BDNF (pBDNF). Methods60 patients with MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 45 min, three times a week. Both depression severity and pBDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication. ResultspBDNF levels increased over time in all three study conditions, though, highest increase was observed in the ECT + EAT condition, and lowest increase was observed in the AET condition. Depressive symptoms decreased in all three conditions over time, though, strongest decrease was observed in the ECT + AET condition. The combination of ECT + AET led to significantly greater remission rates than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression. ConclusionsThe pattern of results suggests that ECT, AET and particularly their combination are promising directions for the treatment of patients suffering from MDD, and that it remains unclear to what extent pBDNF is key and a reliable biomarker for MDD.

Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

Major depressive disorder is a devastating mental illness leading to a lifetime prevalence of higher than 16% on individuals. The treatment delay and inevitable adverse effects are major limitations of current depression interventions. Emerging evidence indicates that curcumin produced significant antidepressant properties in depression in both rodents and humans without adverse effects. Therefore, it is necessary to further clarify the antidepressant actions of curcumin and the underlying mechanism in depressed patients. A total of 108 male adults aged between 31 and 59 years were systematically recruited in Tianjin Anding Hospital. Subjects were administered the Chinese version of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale that measures different scores of depressive symptoms. The subjects were asked to take 2 capsules containing either 1000 mg of curcumin or placebo soybean powder daily for 6 weeks on the basis of their current antidepressant medications. The plasma levels of interleukin 1β, tumor necrosis factor α, brain-derived neurotrophic factor, and salivary cortisol were measured by enzyme-linked immunosorbent assay before and after curcumin or placebo treatment during the 6-week procedure. Chronic supplementation with curcumin produced significant antidepressant behavioral response in depressed patients by reduction of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale scores. Furthermore, curcumin decreases inflammatory cytokines interleukin 1β and tumor necrosis factor α level, increases plasma brain-derived neurotrophic factor levels, and decreases salivary cortisol concentrations compared with placebo group. These findings indicate the potential benefits of further implications of supplementary administration of curcumin to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder.