Plasma BDNF Research Articles

Genetic Variations of Brain Derived Neurotropic Factor Gene With Premenstrual Syndrome Among Pakistani Menarcheal Girls: A Pilot Study

The premenstrual syndrome (PMS) comprises various physical and emotional symptoms which are associated with the menstrual cycle. The emotional changes might be due to the variation in the levels of BDNF especially lower levels of plasma BDNF may be present at the luteal phase of menstrual cycle. To date, no data were present to associate the link between BDNF gene polymorphism and PMS among young Menarcheal females. So, the goal of this investigation is to find out the possible relationship between BDNF gene polymorphism and PMS among young Menarcheal females of Pakistan. A total of 92 menarcheal girls with age range of 11-14yrs met the inclusion criteria. All participants were screened for the depression and PMS using Zung’s depression scale/ Diagnostic and Statistical Manual of Mental Disorders-IV (DSM IV) criteria and world health organization (WHO) criteria for PMS respectively. Genomic DNA was extracted from oral samples by Salting out method and BDNF genotyping was done using PCR-RFLP analysis. Results showed no significant association (χ2=1.685, p-value=0.431) was observed between BDNF genotyping and PMS among menarcheal girls. BDNF (rs6265) AA and GA genotypes did not show significant association with the risk of PMS. Hence, it was concluded that BDNF gene polymorphism may not be associated with the PMS among Pakistani Menarcheal girls

BDNF corrects NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming through KLF2/HK1 pathway in vascular endothelial cells

NLRP3 inflammasome-mediated vascular EC pyroptosis is a key event in the pathogenesis of atherosclerosis. Dysregulation of glucose metabolism is involved in EC dysfunction. Although BDNF plays a protective role in vascular endothelium physiological activity, the mechanisms underlying this activity are not yet clear. In this study, we investigated the role of BDNF in NLRP3 inflammasome-mediated EC pyroptosis and its associated reprogramming of glucose metabolism. HUVECs were treated with human rBDNF under ox-LDL stimulation. rBDNF alleviated ox-LDL-induced NLRP3 inflammasome formation and HUVEC pyroptosis, as evaluated by NLRP3, caspase1-p10, interleukin-18, and interleukin-1β protein levels, co-localization of NLRP3 and apoptosis-associated speck-like protein, and lactate dehydrogenase release. These effects were prevented by tropomyosin receptor kinase B inhibition and KLF2 silencing. The hyper-activation of glycolysis induced by ox-LDL-induced was mitigated by rBDNF via KLF2 as assessed by glucose uptake, lactate production, and extracellular acidification rate. In addition, the BDNF/KLF2 pathway preserved the mitochondrial membrane potential, intracellular reactive oxygen species generation, electron transport chain processing, oxygen consumption rate, and adenosine triphosphate production. Furthermore, KLF2 interacted with HK1 and HK1 overexpression evoked NLRP3 inflammasome formation. At the clinical level, plasma BDNF and lactate levels were measured in 274 patients who underwent computed tomography and coronary angiography for CAD diagnosis. Patients with CAD had lower BDNF and increased lactate levels than those without CAD. In 94 patients with CAD, circulating BDNF levels were inversely associated with lactate levels. In the receiver operating characteristic analysis of CAD, the areas under the curves for 1/BDNF, lactate, and 1/BDNF+lactate were 0.707, 0.702, and 0.753 respectively. These results indicate that BDNF and lactate are linked in atherosclerotic patients, and BDNF inhibits ox-LDL induced NLRP3 inflammasome formation and pyroptosis in HUVECs via KLF2/HK1-mediated glucose metabolism modulation and mitochondrial homeostasis preservation.

Neoadjuvant Chemotherapy Increases Cytotoxic T Cell, Tissue Resident Memory T Cell, and B Cell Infiltration in Resectable NSCLC.

The combination of programmed cell death protein-1 or programmed death-ligand 1 immune checkpoint blockade and chemotherapy has revolutionized the treatment of advanced NSCLC, but the mechanisms underlying this synergy remain incompletely understood. In this study, we explored the relationships between neoadjuvant chemotherapy and the immune microenvironment (IME) of resectable NSCLC to identify novel mechanisms by which chemotherapy may enhance the effect of immune checkpoint blockade. Genomic, transcriptomic, and immune profiling data of 511 patients treated with neoadjuvant chemotherapy followed by surgery (NCT) versus upfront surgery (US) were compared with determined differential characteristics of the IMEs derived from whole-exome sequencing (NCT= 18; US= 73), RNA microarray (NCT= 45; US= 202), flow cytometry (NCT= 17; US= 39), multiplex immunofluorescence (NCT= 10; US= 72), T-cell receptor sequencing (NCT= 16 and US= 63), and circulating cytokines (NCT= 18; US= 73). NCT was associated with increased infiltration of cytotoxic CD8+ T cells and CD20+ B cells. Moreover, NCT was associated with increases in CD8+CD103+ and CD4+CD103+PD-1+TIM3- tissue resident memory T cells. Gene expression profiling supported memory function of CD8+ and CD4+ T cells. However, NCT did not affect T-cell receptor clonality, richness, or tumor mutational burden. Finally, NCT was associated with decreased plasma BDNF (TrkB) at baseline and week 4 after surgery. Our study supports that, in the context of resectable NSCLC, neoadjuvant chemotherapy promotes antitumor immunity through T and B cell recruitment in the IME and through a phenotypic change toward cytotoxic and memory CD8+ and CD4+ memory helper T cells.

Plasma BDNF Levels Following Transcranial Direct Current Stimulation Allow Prediction of Synaptic Plasticity and Memory Deficits in 3×Tg-AD Mice.

Early diagnosis of Alzheimer’s disease (AD) supposedly increases the effectiveness of therapeutic interventions. However, presently available diagnostic procedures are either invasive or require complex and expensive technologies, which cannot be applied at a larger scale to screen populations at risk of AD. We were looking for a biomarker allowing to unveil a dysfunction of molecular mechanisms, which underly synaptic plasticity and memory, before the AD phenotype is manifested and investigated the effects of transcranial direct current stimulation (tDCS) in 3×Tg-AD mice, an experimental model of AD which does not exhibit any long-term potentiation (LTP) and memory deficits at the age of 3 months (3×Tg-AD-3M). Our results demonstrated that tDCS differentially affected 3×Tg-AD-3M and age-matched wild-type (WT) mice. While tDCS increased LTP at CA3-CA1 synapses and memory in WT mice, it failed to elicit these effects in 3×Tg-AD-3M mice. Remarkably, 3×Tg-AD-3M mice did not show the tDCS-dependent increases in pCREBSer133 and pCaMKIIThr286, which were found in WT mice. Of relevance, tDCS induced a significant increase of plasma BDNF levels in WT mice, which was not found in 3×Tg-AD-3M mice. Collectively, our results showed that plasticity mechanisms are resistant to tDCS effects in the pre-AD stage. In particular, the lack of BDNF responsiveness to tDCS in 3×Tg-AD-3M mice suggests that combining tDCS with dosages of plasma BDNF levels may provide an easy-to-detect and low-cost biomarker of covert impairment of synaptic plasticity mechanisms underlying memory, which could be clinically applicable. Testing proposed here might be useful to identify AD in its preclinical stage, allowing timely and, hopefully, more effective disease-modifying interventions.

Plasma BDNF is a more reliable biomarker than erythrocyte omega-3 index for the omega-3 fatty acid enrichment of brain

Enriching brain DHA is believed to be beneficial for the prevention and treatment of several neurological diseases, including Alzheimer’s disease. An impediment in assessing the effectiveness of the treatments is the lack of a reliable biomarker for brain DHA. The commonly used erythrocyte omega-3 index is not suitable for brain because of the involvement of unique transporter at the blood brain barrier (BBB). We recently showed that dietary lysophosphatidylcholine (LPC)-DHA significantly increases brain DHA, which results in increase of brain BDNF. Since there is bidirectional transport of BDNF through the BBB, we tested the hypothesis that plasma BDNF may be used as biomarker for brain DHA enrichment. We altered the brain DHA in rats and mice over a wide range using different dietary carriers of DHA, and the correlations between the increase in brain omega-3 index with the increases in plasma BDNF and the erythrocyte index were determined. Whereas the increase in brain omega-3 index positively correlated with the increase in plasma BDNF, it negatively correlated with the erythrocyte index. These results show that the plasma BDNF is more reliable than the erythrocyte index as biomarker for assessing the effectiveness of omega-3 supplements in improving brain function.

Relationship between occupational aluminium exposure and histone lysine modification through methylation

BackgroundAluminium is an environmental neurotoxin to which human beings are extensively exposed. However, the molecular mechanism of aluminium toxicity remains unclear. MethodsThe changes in cognitive function of aluminum exposed workers under long-term occupational exposure were evaluated, and the relationship between cognitive changes, plasma memory related BDNF and EGR1 protein expression, and variations of epigenetic markers H3K4me3, H3K9me2, H3K27me3 expression levels in blood was explored. ResultsMMSE, DSFT, DST scores in cognitive function and the levels of plasma BDNF and EGR1 protein expression decreased with the increase of blood aluminum level. H3K4me3, H3K9me2, H3K27me3 expression levels in peripheral blood lymphocytes of aluminum exposed workers were statistically different (all P<0.05). H3K4me3, H3K9me2 and H3K27me3 expression levels in lymphocytes were correlated with blood aluminum level. BDNF, EGR1 protein level and H3K4me3, H3K9me2, H3K27me3 expression levels have different degrees of correlation. There was a linear regression relationship between plasma BDNF, H3K4me3 and H3K9me2. H3K9me2 had a greater effect on BDNF than H3K4me3. There is a linear regression relationship between EGR1, H3K4me3 and H3K27me3, and the influence of H3K4me3 on EGR1 is greater than that of H3K27me3 on EGR1. ConclusionAlummnum may regulate the expression of BDNF and EGR1 by regulating H3K4me3, H3K27me3 and H3K9me2, and affect the cognitive function of workers by affecting the expression of BDNF and EGR1.

Effect of exenatide, metformin and folic acid on experimentally induced metabolic–cognitive syndrome in rats

Background: Metabolic syndrome (MetS) and its relationship with cognitive impairment has been the subject of extensive research. Purpose: This study was designed to determine the effect of MetS on cognitive function, and the possibility of modulating this effect by exenatide, metformin and folic acid. Materials and Methods: 30 adult male albino rats were divided in 5 groups. Group (I): received a standard rat chow, group (II): none treated rats with MetS fed with 60% fructose added to the standard rat chow, group (III): rats with MetS treated with exenatide, group (IV): rats with MetS treated with metformin, group (V): rats with MetS treated with folic acid. At the end of the experiment, fasting blood glucose, fasting plasma insulin, HOMA-IR index, serum triglyceride, HDL-C, dopamine and BDNF levels in brain tissue were measured and cognitive performance was assessed by Morris water maze (MWM) test. Results: rats with MetS showed increased levels of fasting blood glucose, fasting plasma insulin, HOMA-IR index, arterial blood pressure, serum triglycerides, decreased HDL-C, dopamine and BDNF and showed memory impairment in MWM test. All treated groups resulted in decrease in fasting blood glucose, fasting plasma insulin, HOMA-IR index, arterial blood pressure, and serum triglycerides and increase in HDL-C, dopamine and BDNF as well as improvement in MWM test. Conclusion: MetS was associated with cognitive impairment. Exenatide, metformin and folic acid improved cognitive function in addition to improvement of metabolic parameters.

Antidepressant-like effect of flaxseed in rats exposed to chronic unpredictable stress.

IntroductionDepression is a serious mental illness. However, a significant proportion of patients with depression fail to achieve remission with antidepressant therapies. This study was conducted to explore the antidepressant‐like effect of flaxseed oil and flour in an animal model with depression‐like behaviors induced by chronic unpredictable stress (CUS).MethodsRats were randomly divided into five groups: normal control (Sham–Sham), CUS plus saline (S‐SN), CUS plus escitalopram (S‐Esc), CUS plus flaxseeds oil (S‐FO), and CUS plus flaxseed flour (S‐FF). Behaviors were tested using sucrose preference test and forced swimming test. The serum BDNF concentration, hippocampal BDNF mRNA, and protein expression were measured by enzyme‐linked immunosorbent assay, real‐time PCR, and Western blot, respectively.ResultsThe sucrose preference rate was significantly higher in S‐FO and S‐FF rats than in S‐SN and S‐Esc rats (p < .01), and lower in S‐Esc rats than in Sham–Sham rats (p < .01). The immobility time was significantly shorter in S‐FO and S‐FF rats than in S‐SN rats (p < .01), and shorter in S‐Esc rats than in S‐SN rats (p < .01). Plasma BDNF concentrations were significantly lower in S‐FO, S‐FF, and S‐Esc rats than in Sham–Sham rats (p < .01); BDNF was lower in S‐FO, S‐FF, and S‐SN rats than in S‐Esc rats. The hippocampal BDNF protein expression was significantly higher in S‐Esc rats than in S‐SN rats (p < .05). The hippocampal BDNF mRNA expression was significantly higher in S‐Esc rats than in S‐SN rats (p < .01). The BDNF gene expression in plasma and the hippocampus negatively correlated with the immobility time (p < .05), but BDNF gene expression in the hippocampus positively correlated with the sucrose preference rate (p < .05).ConclusionFlaxseed oil and flaxseed flour exert antidepressant‐like effect in rats exposed to chronic stress. Flaxseed may have a therapeutic effect on depression.

The effect of combined scalp acupuncture and cognitive training in patients with stroke on cognitive and motor functions.

To investigate the effect of combined scalp acupuncture and cognitive training on cognitive and motor functioning in patients with stroke during the recovery stage. Seventy patients with post-stroke cognitive impairment were randomly divided into an experimental group and a control group. Patients in the experimental group additionally received scalp acupuncture and cognitive training, while the control group received sham scalp acupuncture and cognitive training. The cognitive and motor functioning of all patients were assessed using MMSE, LOTCA, and FMA, before and 12 weeks after treatment. In addition, the plasma BDNF and NGF levels were measured from peripheral blood samples using ELISA kits. After 12 weeks, the MMSE, LOTCA and FMA scores were significantly higher in the experimental group than in the control group. In the experimental group, there was an improvement in the total MMSE score, orientation, spatial executive function, the total LOTCA score, and the score of command of language orientation post-treatment. Significant improvements of BDNF and NGF were found in the experimental group after treatment, while only significant improvements of NGF was found in the control group after treatment. Both BDNF and NGF in the experiment group were higher than those in the control group at the last day of treatment. Combined scalp acupuncture and cognitive training can efficiently enhance cognitive and motor functions in patients with stroke during the recovery stage, which may be a more effective rehabilitation treatment after stroke than routine therapy and rehabilitation training alone.

Depressive symptoms in schizophrenia patients: A possible relationship between SIRT1 and BDNF

ObjectivesDepressive symptoms are commonly seen in schizophrenia. Increasing evidence implicates that both SIRT1 and BDNF closely related to the development of depression. So we here aimed to explore the effect of BDNF and SIRT1 on the depressive symptoms, and also explore the risk factors for the depressive symptoms in schizophrenia patients. MethodsA group of 203 participants (case/controls, 174/29) was recruited in the present work. Significant depression was classified by the CDSS score 7 or above. The psychotic symptoms and cognitive functions in schizophrenia patients were evaluated by PANSS and RBANS respectively. And the plasma concentration of SIRT1 and BDNF were measured in 167 participants (case/controls, 138/29). ResultsCompared to healthy subjects, schizophrenia patients exhibited notably lower levels of BDNF (P < 0.05). And we observed that patients with depression displayed a worse psychotic symptom (P < 0.01), a poorer cognitive function(P < 0.05), as well as lower plasma BDNF and SIRT1 levels (Bonferroni corrected P < 0.05) compared to those no depressive patients. And the SIRT1 levels were positively correlated with BDNF levels in the case group (P < 0.001). And the regression analysis showed that negative symptoms and general psychopathology in PANSS, attention and delayed memory in RBANS, BDNF and SIRT1 were independent risk factors for depressive symptoms in schizophrenia. ConclusionAside from the association with psychotic symptoms, we provided evidence suggesting that low BDNF and SIRT1 concentration value may be responsible for the occurrence of depression in schizophrenic patients.

1817-P: Metabolic Surgery Affects Brain Glucose Metabolism, Cognitive Function, and Neuroplasticity in Humans

Risk of neurodegenerative disorders, cognitive dysfunction and impaired neuroplasticity (NP) is increased in obesity. We evaluated the effect of metabolic surgery (RYGB) on insulin sensitivity, brain glucose utilization, cognitive function and NP. Thirteen obese subjects (BMI 46±4.9 kg/m2; HbA1c 40.1±5.9 mmol/mol; age 42.4±9.8 years) with no history of psychiatric illness and psychoactive drug use and major brain disorders were recruited. Subjects underwent a 75 gr OGTT during a 60 min FDG dynamic brain PET study, standardized neurocognitive tests and NP by psychophysical technique at baseline and 6-months after RYGB. Plasma glucose, insulin, GLP-1, GIP, VIP, BDNF and leptin were measured during OGTT. After RYGB, BMI declined (45.7±1.6 to 34.3±1.6 kg/m2; p&amp;lt;0.001) and insulin sensitivity improved (HOMA-IR 4.7±0.9 to 1.6±0.4; P=0.006). Cerebral glucose metabolic rate (CMRg; by voxel-wise paired analysis) declined in several brain regions (p=0.005, kE&amp;gt;50). Token and Trail Making Test score change correlated with CMRg change in orbitofrontal (r=0.6, r=-0.81), parietal (r=0.64, r=-0.77), temporal (r=0.6, r=-0.78) and visual cortex (r=0.64, r=-0.75), hippocampus (r=0.6, r=-0.71) and caudate/putamen (r=0.64, r=-0.80; all p=0.03 or less), respectively. After RYGB, NP increased (0.01± 0.03 to 0.11±0.04; p=0.008) and correlated with CMRg change in orbitofrontal cortex (r=0.59; p=0.03) and hippocampus (r=0.58; p=0.03). CMRg of several cortical and subcortical areas correlated with HOMA-IR (p&amp;lt;0.001) but not with BMI. GLP-1/GIP levels increased (P&amp;lt;0.002) with no correlation with CMRg, VIP or BDNF levels. Fasting leptin decreased (73.8±45.5 to 14.3±5.9 pmol/l; p&amp;lt;0.008) and correlated with CMRg change in hippocampus (r=0.6; r=0.03). These results show that metabolic surgery modulates CMRg in brain areas involved in cognitive function and neuroplasticity, suggesting reduction of brain glucose utilization decrease may contribute to brain neuroprotection. Disclosure G. Daniele: None. A. Dardano: None. D. Volterrani: None. A. Ciccarone: None. L. Giusti: None. G. Aghakhanyan: None. G. Ceccarini: None. F. Santini: None. C. Moretto: None. P. Binda: None. C. Lunghi: None. M. Morrone: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Board Member; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited.

An increase in plasma brain derived neurotrophic factor levels is related to n-3 polyunsaturated fatty acid efficacy in first episode schizophrenia: secondary outcome analysis of the OFFER randomized clinical trial

RationaleN−3 polyunsaturated fatty acids (n−3 PUFA) influence multiple biochemical mechanisms postulated in the pathogenesis of schizophrenia that may influence BDNF synthesis.ObjectivesA randomized placebo-controlled study was designed to compare the efficacy of a 26-week intervention composed of either 2.2 g/day of n−3 PUFA or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. The secondary outcome measure of the study was to describe the association between n−3 PUFA clinical effect and changes in peripheral BDNF levels.MethodsSeventy-one patients aged 16–35 were enrolled in the study and randomly assigned to the following study arms: 36 to the EPA + DHA group and 35 to the placebo group. Plasma BDNF levels were assessed three times, at baseline and at weeks 8 and 26 of the intervention. BDNF levels were determined in plasma samples using Quantikine Human BDNF ELISA kit. Plasma BDNF level changes were further correlated with changes in the severity of symptoms in different clinical domains.ResultsA significantly greater increase in plasma BDNF levels was observed in the intervention compared to the placebo group (Cohen’s d = 1.54). Changes of BDNF levels inversely correlated with change in depressive symptoms assessed using the Calgary Depression Rating Scale in Schizophrenia (Pearson’s r = − 0.195; p = 0.018).ConclusionsThe efficacy of a six-month intervention with n−3 PUFA observed in first-episode schizophrenia may be related to an increase in BDNF levels, which may be triggered by the activation of intracellular signaling pathways including transcription factors such as cAMP-reactive element binding protein.

Increased levels of plasma IL-1b and BDNF can predict resistant depression patients.

There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence. This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (RD) or Bipolar Affective Disorder (BAD) patients under conventional treatment. The population evaluated was comprised of 34 RD, 43 BAD, and 41 controls. Subclinical atherosclerosis markers were evaluated using ultrasonography, tomography, and exercise stress test. Plasma concentrations of TNFα, IL-1β, IL-6, and BDNF were measured using Luminex100™. The usCRP concentration was measured using turbidimetric immunoassay. IL1B, IL6, and TNFA expression were determined using TaqMan®. For the statistical analysis, the significance level was established at p<0.05. Concerning subclinical atherosclerosis markers, only O2 consumption was reduced in the BAD group (p = 0.001). Although no differences were found in gene expression, BDNF and IL-1β plasma concentration was increased in the RD group (p = 0.002 and p = 0.005, respectively) even with an antidepressant treatment, which suggests that these drugs have no effect in IL-1β secretion and that the inflammasome may play a role in therapy response. Taken together, both BDNF and IL-1β plasma concentrations could be used to the early identification of RD patients.

Probability of TCD-Normalization in the “Drepagreffe” Trial Comparing Transplantation to Chronic Transfusion in Sickle Cell Anemia Children with Abnormal-Transcranial Doppler Is Associated with Lower Ang-2 and BDNF Plasma Levels

Sickle cell anemia (SCA) is a chronic illness that causes an increased risk of stroke and progressive brain and cognitive dysfunction. SCA-related cerebral vasculopathy includes vascular remodeling, abnormal arterial velocities and infarction. We studied the relationship between cytokines, velocities, and blood parameters in SCA-children enrolled in the “Drepagreffe” trial, a French prospective, Mendelian-randomized trial with 2 arms (transfusions/transplantation) defined by random-availability of a HLA-matched sibling. This trial enrolled SCA-children younger than 15, regularly transfused for abnormal-TCD history, with at least one non-SCA sibling, and parents agreeing to HLA-typing and transplantation. Between 12/2010 and 6/2013, 67 SCA-children (7 with stroke history) were enrolled. Thirty-two had a matched-sibling donor (MSD) and were transplanted, while 35 (no donor) were included in the transfusion arm.Hypoxia/angiogenesis and brain injury-related factor expression at 1-year was one of the trial secondary outcome. Elevated plasma BDNF and PDGF-AA have been shown to be significantly associated with high cerebral velocities (Hyacinth 2012). Chronic transfusion has been shown to reduce vascular endothelial activation and thrombogenicity in SCA-children with abnormal-TCD (Hyacinth 2014) but no study has been performed in transplanted SCA-children. Plasma samples were obtained at enrollment and 1-year post-enrollment and stored frozen. The expression of the following cytokines (VEGF, Ang-1, Ang-2, FGFb, HGF, PDGF-BB, BDNF) was assessed with a multiplex immunoassay (Bio-Techne). Ang-2, and BDNF levels were confirmed with specific enzyme-linked immunosorbent assays (ELISA, Bio-Techne). Blood parameters, velocities, ischemic lesions and stenoses were assessed at enrollment and 1-year post-enrollment.At 1-year, the percentage of patients with normalized-TCD (velocities<170cm/sec) was significantly higher in transplanted patients than in those maintained on chronic transfusion (27/32 (84%) vs 17/35 (49%), respectively; p=0.001). As shown (Table), leukocytes, neutrophils, platelets, reticulocytes, LDH, bilirubin, ferritin, HbS% were highly significantly lower in transplanted children than in those maintained on chronic transfusion, while hemoglobin and HbA% were highly significantly higher. Ang-2 and HGF were significantly lower in transplanted children than in those on chronic transfusion (p<0.001 and p=0.002, respectively). Velocities recorded in the artery with the highest values were significantly positively correlated with Ang-2 (r=0.385, p=0.015) and BDNF (r=0.444, p=0.005). Logistic regression analysis showed that TCD-normalization was significantly associated with the transplantation arm (OR=5.72 (95%CI:1.79-18.27); p=0.003). High hemoglobin (OR=1.49 per 1g/dL increase; 95%CI: 1.08-2.06; p=0.014) and HbA% (OR=1.05 per1% increase; 95%CI: 1.01-1.10; p=0.014) were significantly positively associated with TCD-normalization, but not independently. Higher levels of Ang-2 (OR=0.51 per 1 pg/mL increase, 95%CI:0.29-0.91; p=0.023) and BDNF (OR=0.69 per 1 pg/mL increase, 95%CI:0.50-0.94; p=0.02) were negatively and independently significantly associated with TCD-normalization. Multivariate analysis, also including the treatment arm, showed that BDNF remained an independent risk factor for a lack of TCD-normalization (OR=0.65, 95%CI:0.45-0.92: p=0.017).This study confirms the association between high levels of BDNF and high velocities, and suggests that transplantation increases the likelihood of TCD-normalization compared to transfusion, and is associated with reduced Ang-2 expression in plasma, which may reflect improved brain oxygenation. DisclosuresThuret:Addmedica: Research Funding; bluebird bio: Research Funding; Novartis: Research Funding. Pondarré:Addmedica: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Blue Bird Bio: Honoraria. Bernaudin:AddMedica: Honoraria; Pierre fabre: Research Funding; Cordons de Vie: Research Funding; BlueBirdBio: Consultancy.

PO-238 Urinary metabolomics study on the anti-depression effect of different exercise modes on CUMS model rats

Objective To study the effects of different exercise modes on CUMS depression model rats by 1H-NMR metabolomics technique, and to explore the mechanism of exercise anti-depression and to find the best exercise mode.&#x0D; Methods Forty-eight male SD rats were divided into control group (group C), model group (group M), aerobic exercise group (group A), and resistance exercise group (group R), 12 per group. The group C was routinely reared, chronic mild unpredictable stress + orphaned 8 weeks to establish a depression model of CUMS rats. In the 5th week of modeling, rats in group A and group R were trained in aerobic and resistance exercise for 4 weeks. The changes of body mass were observed during the experiment. The effects of exercise on the behavior of CUMS rats were observed by sucrose preference experiment and open field experiment. The levels of plasma BDNF, CORT and 5-HT were measured to reveal the pathological changes of the model. 1H-NMR metabolomics techniques combined with multivariate statistical analysis methods were used to investigate the regulation of urinary endogenous metabolites and the regulation of metabolic pathways in CUMS depression rats. &#x0D; Results 1) After four weeks of modeling, compared with the group C, the body weight, saccharide water preference rate, the crossing number and the number of erectings in the group M, group A and group R were significantly lower (P&lt;0.05 or P&lt; 0.01), indicating that the modeling was successful; after eight weeks of modeling, compared with the group C, the body weight, saccharide water preference rate, the crossing number and the number of erectings in the group M, was significantly lower (P&lt;0.01). There was no significant difference in the group A and group R. 2)Compared with group C, the levels of BDNF and 5-HT in group M were significantly decreased (P&lt;0.05 or P&lt;0.01), the level of CORT was significantly increased (P&lt;0.01), and the levels of BDNF, 5-HT and CORT in group A were not significantly different, the CORT levels were significantly increased in group R(P &lt;0.01), BDNF and 5-HT levels were not significantly different; compared with group M, BDNF, 5-HT levels in group A were significantly increased (P &lt;0.05) and the level of CORT was significantly decreased (P&lt;0.01), the levels of BDNF and 5-HT in group R were significantly increased (P&lt;0.01), but there was no significant difference in CORT level. Compared with group A, the levels of BDNF and 5-HT in group R were not significant,but CORT levels increased significantly (P&lt;0.05). 3)A total of 14 potential biomarkers in the urine of CUMS depression model rats were found . Compared with group C, the levels of leucine, valine, lactic acid, citric acid, inositol, pyruvic acid, β-hydroxybutyric acid, acetoacetic acid, trimethylamine, pantothenic acid, β-hydroxyisovaleric acid, alanine and succinic acid in the urine of group M were significantly increased, and the level of α-ketoglutaric acid was significantly decreased (P&lt;0.05 or P&lt;0.01). Group A can significantly callback 8 potential biomarkersof leucine, lactic acid, citric acid, pyruvic acid, β-hydroxybutyric acid, alanine, lactic acid and pantothenic acid (P&lt;0.05 or P&lt;0.01) , the group R can significantly callbackt the 6 potential biomarkers of lactic acid, acetoacetic acid, inositol, trimethylamine, β-hydroxy isovaleric acid and alanine. Two types of exercise can regulate urinary metabolites in depressed rats. 4) 1H-NMR metabolic pathway analysis showed that aerobic exercise mainly improves the urine metabolism of depressed rats by regulating TCA cycle, pantothenic acid and COA biosynthesis, and pyruvate metabolism. The resistance exercise mainly improved the urine metabolism characteristics of depressed rats by regulating the synthesis and degradation of ketone bodies, pyruvate metabolism and inositol phosphate metabolism.&#x0D; Conclusions Aerobic exercise and resistance exercise all can effectively improve depressive symptoms, adjust the urine biomarkers of depressed rats to varying degrees, which may be related to different metabolic pathways involved in exercise modes.&#x0D;

Effect of electroconvulsive therapy on brain-derived neurotrophic factor levels in patients with major depressive disorder.

ObjectivesBrain‐derived neurotrophic factor (BDNF) has been associated with depression and its treatment response. The aim of the present study was to explore the effect of electroconvulsive therapy (ECT) on serum and plasma BDNF levels and change of Montgomery–Asberg Depression Rating Scale (MADRS) and their associations in patients with major depressive disorder (MDD).MethodsThe study included thirty patients suffering from MDD. Their serum and plasma BDNF levels were examined before ECT (baseline) and after the first, fifth, and last ECT session. The severity of the depression and the response to ECT were measured with MADRS.ResultsElectroconvulsive therapy caused no significant changes in serum BDNF levels. Plasma BDNF levels decreased during the fifth ECT session between the baseline and the 2‐hr samples (p = 0.019). No associations were found between serum or plasma BDNF levels and remission. The correlations between plasma and serum BDNF levels in each measurement varied between 0.187 and 0.636.ConclusionsNeither serum nor plasma BDNF levels were systematically associated with the clinical remission. However, the plasma BDNF levels somewhat varied during the ECT series. Therefore, the predictive value of BDNF for effects of ECT appears to be at least modest.

Reduced brain-derived neurotrophic factor is associated with childhood trauma experiences and number of depressive episodes in severe mental disorders

BackgroundAlthough several studies have found reduced plasma BDNF levels in patients with severe mental disorders, the sample sizes have been small and have exhibited variation and heterogeneity. Furthermore, long-term neurobiological changes following childhood trauma and clinical severity have been linked to a reduction in BDNF levels. Accordingly, we aim to clarify, using the largest sample size to date, the role of plasma BDNF in individuals with severe mental disorders in relation to the number of episodes, current remission status, and childhood trauma experiences. MethodsThe study sample comprised 1446 individuals (schizophrenia: SZ [n = 589]; bipolar disorder: BD [n = 254]; and healthy control: HC [n = 603]) all recruited from the same catchment area. A subsample (N = 629) of this larger group had a history of childhood trauma, and some (N = 195) participated in a one-year follow-up study. The level of BDNF in plasma was measured, and childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Diagnoses and episodes were obtained using the Structured Clinical Interview (SCID). ResultsPatients with SZ or BD had lower levels of plasma BDNF than did the HC group (p = 0.002, p = 0.003, respectively). Within patients, reduced plasma BDNF levels were associated with more depressive episodes (p = 0.04). Longer time in remission after depressive episodes was associated with higher plasma BDNF levels (p = 0.02), and patients reporting childhood sexual abuse exhibited lower plasma BDNF levels (p = 0.049) than patients without sexual abuse. ConclusionOur study confirms that patients with a severe mental disorder exhibit reduced BDNF levels. While the strongest reduction in BDNF was observed in patients reporting childhood sexual abuse, reduced BDNF levels were also associated with more depressive episodes. Accordingly, further studies are warranted to determine whether treatment that increases BDNF levels may be beneficial to these individuals.

Dance training is superior to repetitive physical exercise in inducing brain plasticity in the elderly.

Animal research indicates that a combination of physical activity and sensory enrichment has the largest and the only sustaining effect on adult neuroplasticity. Dancing has been suggested as a human homologue to this combined intervention as it poses demands on both physical and cognitive functions. For the present exploratory study, we designed an especially challenging dance program in which our elderly participants constantly had to learn novel and increasingly difficult choreographies. This six-month-long program was compared to conventional fitness training matched for intensity. An extensive pre/post-assessment was performed on the 38 participants (63–80 y), covering general cognition, attention, memory, postural and cardio-respiratory performance, neurotrophic factors and–most crucially–structural MRI using an exploratory analysis. For analysis of MRI data, a new method of voxel-based morphometry (VBM) designed specifically for pairwise longitudinal group comparisons was employed. Both interventions increased physical fitness to the same extent. Pronounced differences were seen in the effects on brain volumes: Dancing compared to conventional fitness activity led to larger volume increases in more brain areas, including the cingulate cortex, insula, corpus callosum and sensorimotor cortex. Only dancing was associated with an increase in plasma BDNF levels. Regarding cognition, both groups improved in attention and spatial memory, but no significant group differences emerged. The latter finding may indicate that cognitive benefits may develop later and after structural brain changes have taken place. The present results recommend our challenging dance program as an effective measure to counteract detrimental effects of aging on the brain.

Altered cardiovascular function is related to reduced BDNF in Parkinson’s disease

ABSTRACTBrain-derived neurotrophic factor (BDNF) has been linked to cardiovascular health and function, however, the exact role is yet to be understood. The current study examined the relationship of circulatory BDNF with vascular function in Parkinson’s disease (PD).ELISA was used to determine plasma BDNF in PD patients and healthy control (CT). Additionally, forearm resting blood flow (RBf), vascular resistance (RVr), venous capacitance (RVc), and venous outflow (RVo) as well as post occlusion blood flow (OcBf), vascular resistance (OcVr), venous capacitance (OcVc), and venous outflow (OcVo) were obtained using strain-gauge plethysmography.Simple linear regression showed that being PD patient can predict (p < 0.05) 12.9% of BDNF, 16.8% of RVc, 15.0% of OcVc, and 13.6% of OcVo. Subsequent stepwise regression included BDNF, RVc, OcVc, and OcVo, showed that being PD patient predicted (p < 0.05) 58.0% of BDNF, 47.7% of OcVo, and 15.1% of OcVc. Another simple linear regression demonstrated that BDNF predicted (p < 0.05) 18.5% of OcBf, 22.0% of OcVr, and 24.1% of OcVc in PD. In a subsequent stepwise linear regression, BDNF explained 26% ofOcVr (p = 0.008) and 42% of OcVc (p = 0.002) in PD.The study showed that BDNF is reduced and related to altered vascular function in PD. The results suggest that BDNF might contribute to preserving and maybe improving vascular function in PD.

Tai Chi Improves Cognition and Plasma BDNF in Older Adults With Mild Cognitive Impairment: A Randomized Controlled Trial

Background. Effects of Tai Chi (TC) on specific cognitive function and mechanisms by which TC may improve cognition in older adults with amnestic mild cognitive impairment (a-MCI) remain unknown. Objective. To examine the effects of TC on cognitive functions and plasma biomarkers (brain-derived neurotrophic factor [BDNF], tumor necrosis factor-α [TNF-α], and interleukin-10 [IL-10]) in a-MCI. Methods. A total of 66 older adults with a-MCI (mean age = 67.9 years) were randomized to either a TC (n = 33) or a control group (n = 33). Participants in the TC group learned TC with a certified instructor and then practiced at home for 50 min/session, 3 times/wk for 6 months. The control group received educational material that covered information related to cognition. The primary outcome was cognitive performance, including Logical Memory (LM) delayed recall, Block Design, Digit Span, and Trail Making Test B minus A (TMT B-A). The secondary outcomes were plasma biomarkers, including BDNF, TNF-α, and IL-10. Results. At the end of the trial, performance on the LM and TMT B-A was significantly better in the TC group compared with the control group after adjusting for age, gender, and education (P < .05). Plasma BDNF level was significantly increased for the TC group, whereas the other outcome measures were similar between the 2 groups after adjusting for age and gender (P < .05). Conclusions. TC training significantly improved memory and the mental switching component of executive function in older adults with a-MCI, possibly via an upregulation of BDNF.