Plasma Brain-derived Neurotrophic Factor Levels Research Articles

Association Between Objectively Measured Physical Activity and Plasma BDNF in Adolescents: DADOS Study

Brain-derived neurotrophic factor (BDNF) is suggested to play a key role in moderating the benefits of physical activity (PA) on cognition. Previous research found that PA may have an impact on peripheral BDNF expression. The aim of our study was to analyze the association between objectively measured PA with circulating BDNF in a group of active adolescents. Two hundred thirty-four adolescents (132 boys) aged 13.9 ± 0.3years old from the DADOS study were included in this cross-sectional analysis. PA was assessed by GENEActiv triaxial accelerometer. Participants wore the accelerometer on their non-dominant wrist for 6 consecutive 24-h days, including weekends. PA was expressed as the average (min/day) of light, moderate, and vigorous PA. Fasting plasma BDNF concentrations at rest were measured using an enzyme-linked immunosorbent assay. Partial correlations and linear regression analyses were performed with a significance level established at p < 0.05. No correlations were found between BDNF and PA variables. Plasma levels of BDNF at rest were not significantly associated with daily PA in either boys or girls (p > 0.05). Based on previous research and our own data, the association between daily PA and baseline levels of BDNF remains inconclusive. Further research is needed to shed light on the relationship between regular PA and BDNF in adolescents.

Serum hs-CRP, YKL-40 and brain-derived neurotrophic factor (BDNF) associated biomarkers in non-dipper hypertension profile?

Abstract Background: Twenty-four hours dynamic blood pressure (BP) behaviour displays dipper profile defined as nocturnal systolic BP (SBP) reduction&gt;10% compared to daytime. Non-dipper profile, nocturnal absence of SBP fall, associates an increased cardiovascular risk. We investigated the concomitant association of inflammatory bio-markers - high-sensitivity- C-reactive protein (hs-CRP), Human Chitinase3-like1 (YKL-40) and autonomic nervous system (total brain-derived neurotrophic factor, BDNF) with respect to non-dipping blood pressure status. Material and method: Using 24h automatic BP measurements, 80 known hypertensive patients were divided into two groups: dipper group included fifty-one dipper patients (age 55.6 ±13.5 years) and non-dipper group consisted of 29 non-dipper subjects (62.07±12.03 years). Serum levels of hs-CRP were evaluated with enhanced immunoturbidimetric assay. Plasma levels of YKL-40 were measured by commercial sandwich ELISA using microplate coated with a monoclonal antibody for CHI3L1. Plasma levels of total BDNF were determined using quantitative sandwich enzyme-linked immunoassay. Statistical analysis of obtained data was performed. Results: In the non-dipper group, a significant positive association with age over 60 years, hs-CRP values above 1.90 mg/dl was observed along with increased mean values of YKL-40. Non-dipper status is independently and statistically significantly associated with elevated levels of hs-CRP (OR: 3.248, 95% CI: 1.022-10.317, p=0.046) in multivariate odds ratio analysis. No statistically significant positive association between a median total BDNF plasma level of 1430 pg/ml and the non-dipper hypertension profile was identified. Conclusion: Our study demonstrated that patients over 60 years, in particular, have a higher probability to present a non-dipping pattern of hypertension. hs-CRP and YKL-40 values are more likely to increase in the non-dipping hypertensive patients, and hs-CRP values above 1.9 mg/dl can identify the presence of a non-dipper blood pressure profile.

Correlates of neurocognitive functions in individuals at ultra-high risk for psychosis - A 6-month follow-up study

Cognitive deficits are evident at the prodromal phase of psychosis. It has been noted that brain-derived neurotrophic factor (BDNF) is correlated with cognition in both preclinical and clinical studies. However, to our knowledge, no study has evaluated blood BDNF levels and their association with cognitive impairment in individuals at ultra-high risk for psychosis (UHR). We included 13 individuals at UHR and 30 healthy controls (HC) matched by sex, age, and educational level. Plasma BDNF levels were measured at baseline and 6 months. Neurocognitive functions (executive functions, speed of processing, verbal learning and memory, working memory) were examined at 6 months. Regression analyses were conducted to examine the relationship between BDNF levels and cognitive performance. BDNF levels were lower in UHR group than in HC group both at baseline and at 6 months (P = 0.001, and P = 0.007, respectively). There were no associations between plasma BDNF levels and all of the cognitive domains in both groups. Our findings showed that peripheral BDNF levels were not related to cognitive deficits in UHR and HC groups while the lower BDNF level in the former persisted up to 6 months. Further research is needed in a large sample.

Plasma and serum brain-derived neurotrophic factor (BDNF) levels and their association with neurocognition in at-risk mental state, first episode psychosis and chronic schizophrenia patients

Objectives: Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive processes. Since cognitive deficits are a core feature of psychotic disorders, the investigation of BDNF levels in psychosis and their correlation with cognition has received increased attention. However, there are no studies investigating BDNF levels in individuals with an at-risk mental state (ARMS) for psychosis. Hence, the aims of the present study were: (1) assessing peripheral BDNF levels across different (potential) stages of psychosis; (2) investigating their association with cognition.Methods: Plasma and serum BDNF levels and neuropsychological performance were assessed in 16 ARMS, six first-episode psychosis (FEP), and 11 chronic schizophrenia (CS) patients. Neuropsychological assessment covered intelligence, verbal memory, working memory, attention and executive functioning.Results: Both plasma and serum BDNF levels were highest in CS, intermediate in FEP and lowest in ARMS. Multiple regression analysis revealed a significant positive association of plasma BDNF levels with planning ability across all groups.Conclusions: The lower peripheral BDNF levels in ARMS compared to FEP and CS might point towards an important drop of this neurotrophin prior to the onset of frank psychosis. The associations of peripheral BDNF with planning-abilities match previous findings.

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.

Impact of Rye Kernel-Based Evening Meal on Microbiota Composition of Young Healthy Lean Volunteers With an Emphasis on Their Hormonal and Appetite Regulations, and Blood Levels of Brain-Derived Neurotrophic Factor.

Rye kernel bread (RKB) evening meals improve glucose tolerance, enhance appetite regulation and increase satiety in healthy volunteers. These beneficial effects on metabolic responses have been shown to be associated with increased gut fermentation. The present study aimed to elucidate if RKB evening meals may cause rapid alterations in microbiota composition that might be linked to metabolic-, immune-, and appetite- parameters. Gut-brain axis interaction was also studied by relating microbiota composition to amount of brain-derived neurotrophic factor (BDNF) in blood plasma. Nineteen healthy volunteers, ten women and nine men aged 22–29 years, BMI < 25 (NCT02093481) participated in the study performed in a crossover design. Each person was assigned to either white wheat bread (WWB) or RKB intake as a single evening meal or three consecutive evenings. Stool and blood samples as well as subjective appetite ratings were obtained the subsequent morning after each test occasion, resulting in four independent collections per participant (n = 76). DNA was extracted from the fecal samples and V4 hypervariable region of the bacterial 16S rRNA genes was sequenced using next generation sequencing technology. Higher abundance of Prevotella and Faecalibacterium with simultaneous reduction of Bacteroides spp. were observed after RKB meals compared to WWB. The associations between metabolic test variables and microbiota composition showed a positive correlation between Bacteroides and adiponectin levels, whereas only Prevotella genus was found to have positive association with plasma levels of BDNF. These novel findings in gut-brain interactions might be of importance, since decreased levels of BDNF, that plays an essential role in brain function, contribute to the pathogenesis of several major neurodisorders, including Alzheimer's. Thus, daily consumption of Faecalibacterium- and/or Prevotella-favoring meals should be investigated further for their potential to prevent neurodegenerative processes in the brain.

Impact of prolonged neuromuscular electrical stimulation on metabolic profile and cognition-related blood parameters in type 2 diabetes: A randomized controlled cross-over trial

AimsThis study aimed to examine the effect of prolonged neuromuscular electrical stimulation (NMES) on the metabolic profile and cognition-related blood parameters in patients with type 2 diabetes mellitus (T2DM). MethodsFourteen patients with T2DM (63.2 ± 3.0 years, 76.1 ± 3.5 kg) participated in a randomized controlled cross-over study, in which 8-week-long NMES interventions were performed on both legs. The NMES training protocol consisted of 40-min sessions, 5 days per week, for 8 weeks. The relative changes in glucose and lipid profiles, and cognition-related blood parameters were evaluated. ResultsNMES training induced significant changes in the fasting glucose concentration (p < 0.05) and percent body fat (p < 0.05), although there were no significant changes in HbA1c and blood lipid levels (p ≥ 0.05). The change in plasma brain-derived neurotrophic factor (BDNF) levels was significantly higher in the NMES period than in the control period (p < 0.05). ConclusionsThis study showed that an 8-week NMES training program could induce greater changes in the blood glucose concentration, percent body fat, and plasma BDNF levels than the control intervention in patients with T2DM. NMES training might prove to be an alternative exercise method for patients who might have difficulties in performing adequate voluntary exercise.

Intravenous infusion of xenon-containing liposomes generates rapid antidepressant-like effects

AimSimilar to ketamine, xenon gas acts as a glutamatergic N-methyl-d-aspartate receptor antagonist, but devoid of propensity to cause untoward effects. Herein, we loaded xenon gas into a liposomal carrier called xenon-containing liposomes (Xe-liposome) for systemic delivery, and investigated its effect as an antidepressant and also analyzed synaptic biomarkers including brain-derived neurotrophic factor (BDNF), protein kinase B (AKT), mammalian target of rapamycin (mTOR), protein kinase C (PKC) and extracellular signal-regulated kinase-1/2 (ERK1/2) in blood and brain. MethodsXe-liposomes (15 μl/mg) were prepared by a pressurized freeze-thaw method, and injected via the lateral tail vein (0.6 mL/rat) in male Wistar rats. The uncaging of xenon gas from circulating Xe-liposome was facilitated by continuous ultrasound application externally on the neck over the internal common carotid artery. One-hour after Xe-liposome infusion, animals were assessed for depression-like behaviors using a forced swimming test (FST), and spontaneous locomotor activity. Blood, as well as frontal cortex and hippocampal samples were obtained for immunoblotting and/or enzyme-linked immune sorbent assays. ResultsAcute intravenous infusion of Xe-liposome, at 6 mg/kg, showed an increase in swimming time in the FST (p < 0.006), indicating antidepressant-like phenotypes. Higher doses of Xe-liposomes (9 mg/kg) failed to improve swimming duration. This behavioral discrepancy was not associated with locomotion aberrations, as gross activity of rats remained similar for both doses. In biochemical analyses of frontal cortex, protein levels of BDNF increased by 64%, and enhanced phosphorylation of AKT (43%) and mTOR (93%) was observed at the 6 mg/kg dose level of Xe-liposomes, while these biomarkers and phosphorylated PKC and ERK1/2 levels remained unchanged at the higher dose. Moreover, Xe-liposomal treatment did not change the plasma and protein levels of BDNF, and phosphorylated AKT, mTOR, PKC and ERK1/2 hippocampal expressions. ConclusionXe-liposomes mediate a rapid antidepressant-like effect through activation of AKT/mTOR/BDNF signaling pathway.

Exercise Leads to Better Clinical Outcomes in Those Receiving Medication Plus Cognitive Behavioral Therapy for Major Depressive Disorder.

The aim of this study is to investigate the effects of exercise as an add-on therapy with antidepressant medication and cognitive behavioral group therapy (CBGT) on treatment outcomes in low-active major depressive disorder (MDD) patients. We also explored whether exercise reduces the residual symptoms of depression, notably cognitive impairment and poor sleep quality, and aimed to identify putative biochemical markers related to treatment response. Sixteen low-active MDD patients were recruited from a mental health day treatment program at a local hospital. Eight medicated patients performed an 8-week exercise intervention in addition to CBGT, and eight medicated patients attended the CBGT only. Twenty-two low-active, healthy participants with no history of mental health illness were also recruited to provide normal healthy values for comparison. Results showed that exercise resulted in greater reduction in depression symptoms (p = 0.007, d = 2.06), with 75% of the patients showing either a therapeutic response or a complete remission of symptoms vs. 25% of those who did not exercise. In addition, exercise was associated with greater improvements in sleep quality (p = 0.046, d = 1.28) and cognitive function (p = 0.046, d = 1.08). The exercise group also had a significant increase in plasma brain-derived neurotrophic factor (BDNF), p = 0.003, d = 6.46, that was associated with improvements in depression scores (p = 0.002, R2 = 0.50) and sleep quality (p = 0.011, R2 = 0.38). We provide evidence that exercise as an add-on to conventional antidepressant therapies improved the efficacy of standard treatment interventions. Our results suggest that plasma BDNF levels and sleep quality appear to be good indicators of treatment response and potential biomarkers associated with the clinical recovery of MDD.

Plasma brain-derived neurotrophic factor (pBDNF) and executive dysfunctions in patients with major depressive disorder

Objectives: Executive dysfunctions are frequently seen in patients with major depressive disorder (MDD) and normalise in many cases during effective antidepressant therapy. This study investigated whether a normalisation of executive dysfunctions during antidepressant treatment correlates with or can be predicted by clinical parameters or levels of brain-derived neurotrophic factor (BDNF).Methods: In 110 MDD patients with executive dysfunctions (percentile <16), executive functions and plasma BDNF levels were analysed at baseline, and days 14 and 56 of an antidepressant treatment. BDNF exon IV and P11 methylation status was studied at baseline.Results: Eighty patients (73%) experienced a normalisation of executive dysfunctions, while 30 (27%) suffered from persistent dysfunctions until day 56. Patients with persistent dysfunctions had significantly higher HAMD scores at days 14 and 56, and lower plasma BDNF levels at each time point than patients with a normalisation of dysfunctions (F1= 10.18; P = 0.002). This was seen for verbal fluency, but not processing speed. BDNF exon IV and p11 promoter methylation was not associated with test performance.Conclusions: Our results corroborate a concomitant amelioration of executive dysfunctions with successful antidepressant therapy and support a role of BDNF in the neural mechanisms underlying the normalisation of executive dysfunctions in MDD.ClinicalTrials.gov number: NCT00974155; EudraCT: 2008-008280-96

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.

Exercise-induced time-dependent changes in plasma BDNF levels in people with schizophrenia

Objective: To investigate the short and long-term outcomes of a concurrent exercise protocol (CEP) on plasma Brain-derived neurotrophic factor (BDNF) levels and the effect of this intervention in the self-esteem and mental health in people with schizophrenia (SZ).

Potential Biomarkers with Plasma Cortisol, Brain-derived Neurotrophic Factor and Nitrites in Patients with Acute Ischemic Stroke

Acute Ischemic Stroke (AIS) represents an economic challenge for health systems all over the globe. Changes of neuroactive steroids have been found in different neurological diseases. We have previously demonstrated that old patients with AIS show changes of plasma cortisol and estradiol concentrations, in that increased steroid levels are associated with a deterioration of neurological status and a worse cognitive decline. The present study assessed in patients with AIS if changes of behavior, Brain-Derived Neurotrophic Factor (BDNF) and Nitrites (NO-2) bear a relationship with the degree of hypercortisolism. We recruited patients hospitalized within the first 24 hours of AIS. Subjects were divided into two groups, each one composed of 40 control subjects and 40 AIS patients, including men and women. The neurological condition was assessed using the National Institute of Health Stroke Scale (NIHSS) and the cognitive status with the Montreal Cognitive Assessment (MoCA). The emotional status was evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS), whereas the Modified Rankin Scale (MRS) was used to determine the functional condition. BDNF and NO-2 plasma levels were measured by ELISA and the Griess reaction method, respectively. We found that in AIS patients, increased plasma cortisol was negatively correlated with plasma BDNF and NO-2 levels, neurological condition, cognition, functional responses and emotional status, suggesting a relationship between the declines of clinical, behavioral and blood parameters with stress-induced cortisol elevation. Nitrites and BDNF may represent potential biomarkers for cortisol negative effects on the area of cerebral ischemia and penumbra, potentiating ischemic cell damage.

Brain-Derived Neurotrophic Factor and Major Depressive Disorder: Evidence from Meta-Analyses.

Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) is associated with the pathophysiology of major depressive disorder (MDD). In this mini review, we explored the association between BDNF and MDD using meta-analytic evidence. Our findings indicated that the Val66Met polymorphism in the BDNF gene was not associated with MDD or hippocampal volume in patients with MDD. However, plasma/serum levels of BDNF were decreased in patients with acute MDD compared with healthy controls. Both antidepressant treatment and electroconvulsive therapy increased plasma and serum levels of BDNF in patients with MDD. Val66Met polymorphism in the BDNF gene was associated with an antidepressant response in patients with MDD. Taken together, we did not detect any plausible evidence regarding Val66Met polymorphism in the BDNF gene contributing to a risk of MDD. However, peripheral BDNF levels are decreased in patients with MDD, and the polymorphisms are associated with treatment response. In conclusion, BDNF is best understood to be a biomarker for the state of MDD and its treatment response rather than a risk factor for MDD.

Plasma Brain Derived Neurotrophic Factor Level and Its Gene Polymorphism in Toxic Suicidal Behavior

Suicide represents a major health problem, it is suggested that multiple factors influence the rate of suicide. Brain derived neurotrophic factor (BDNF) is considered a reliable biological marker of suicide. Its level decreases in all suicidal victims whether or not they are suffering from psychiatric troubles. The objective of this work was to compare BDNF levels and single nucleotide polymorphism in suicidal and non-suicidal groups to explore whether suicide is related to BDNF related mechanisms. Plasma BDNF levels were screened in conjunction with tracking of the 196 G/A (val66met, rs6265) polymorphism in 89 suicidal patients that visited the toxicology unit and 89 control. The pattern of gene polymorphism did not show significant differences between suicidal patients and control. However, the plasma BDNF levels were higher in suicidal cases. It can be concluded that the combined assessment of BDNF showed no difference in genotyping between suicide and control groups. However, higher levels of plasma BDNF were detected in the samples taken from suicide attempters.

Inflammatory biomarkers responses after acute whole body vibration in fibromyalgia.

The aims of this study were 1) to characterize the intensity of the vibration stimulation in women diagnosed with fibromyalgia (FM) compared to a control group of healthy women (HW) matched by age and anthropometric parameters, and 2) to investigate the effect of a single session of whole body vibration (WBV) on inflammatory responses. Levels of adipokines, soluble tumor necrosis factor receptors (sTNFr1, sTNFr2), and brain-derived neurotrophic factor (BDNF) were determined by enzyme-linked immunosorbent assay. Oxygen consumption (VO2) was estimated by a portable gas analysis system, heart rate (HR) was measured using a HR monitor, and perceived exertion (RPE) was evaluated using the Borg scale of perceived exertion. Acutely mild WBV increased VO2 and HR similarly in both groups. There was an interaction (disease vs vibration) in RPE (P=0.0078), showing a higher RPE in FM compared to HW at rest, which further increased in FM after acute WBV, whereas it remained unchanged in HW. In addition, there was an interaction (disease vs vibration) in plasma levels of adiponectin (P=0.0001), sTNFR1 (P=0.000001), sTNFR2 (P=0.0052), leptin (P=0.0007), resistin (P=0.0166), and BDNF (P=0.0179). In conclusion, a single acute session of mild and short WBV can improve the inflammatory status in patients with FM, reaching values close to those of matched HW at their basal status. The neuroendocrine mechanism seems to be an exercise-induced modulation towards greater adaptation to stress response in these patients.

Plasticity after pediatric cochlear implantation: Implication from changes in peripheral plasma level of BDNF and auditory nerve responses

IntroductionSensory neural hearing loss could lead to some structural and physiological changes in the auditory pathways, such as alteration in the expression of neurotrophins. These factors, especially Brain-Derived Neurotrophic Factor (BDNF), play an important role in synaptic functions and experience-related plasticity. Restoring cochlear function after hearing loss is possible through cochlear implantation (CI). Evaluation of the blood concentration changes of neurotrophins as prerequisites of plasticity could help scientists to determine the prognosis of CI as in the candidacy procedure or enhancing prosthesis function by adding the exact needed amount of BDNF to the electrode array. MethodsHere we have studied the plasma BDNF concentration before CI surgery and 6 months after using CI device in 15 pediatric CI recipients and compared this level with changes of BDNF concentration in 10 children who were using hearing aid (H.A). In addition, we searched for a possible correlation between post-surgery plasma BDNF concentration and electrical compound action potential (ECAP) and comfort-level (C-level) thresholds. ResultsPlasma BDNF concentration in children with CI increased significantly after CI surgery, while this difference in H.A group was not significant. Analysis of repeated measures of ECAP and C-level thresholds in CI group showed that there were some kinds of steadiness during follow- up sessions for ECAP thresholds in basal and E16 of middle electrodes, whereas C-level thresholds for all selected electrodes increased significantly up to six months follow-up. Interestingly, we did not find any significant correlation between post-surgery plasma BDNF concentration and ECAP or C-level threshold changes. ConclusionIt is concluded that changes in C-level threshold and steady state of ECAP thresholds and significant changes in BDNF concentration could be regarded as an indicator of experienced-related plasticity after CI stimulation.

Evaluation of plasma brain-derived neurotrophic factor levels and self-perceived cognitive impairment post-chemotherapy: a longitudinal study

BackgroundPreliminary evidence suggests that changes in plasma brain-derived neurotrophic factor (BDNF) levels may contribute to the occurrence of chemotherapy-associated cognitive impairment (CACI), and a previous study suggested that carriers of the BDNF Met homozygous genotype are protected from CACI.MethodsThis multicenter, prospective cohort study involved chemotherapy-receiving early-stage breast cancer (ESBC) patients. Self-perceived cognitive function was longitudinally assessed using the validated FACT-Cog (ver. 3) across three time points: Prior to chemotherapy (T1), during chemotherapy (T2), and at the end of chemotherapy (T3). Plasma BDNF levels were quantified using enzyme-linked immunosorbent assay. Genotyping was performed using Sanger Sequencing.ResultsA total of 51 chemotherapy-receiving ESBC patients (mean age: 52.6 ± 9.5 years) were recruited, and 11 patients (21.6%) reported subjective cognitive impairment post-chemotherapy. Overall, there was a reduction in median plasma BDNF levels over time (T1: 5423.0 pg/ml; T2: 5313.6 pg/ml; T3: 4050.3 pg/ml; p < 0.01). After adjusting for confounding factors, longitudinal analysis revealed that BDNF levels were associated with self-reported concentration deficit (p = 0.032). Carriers of Val/Val (p = 0.011) and Val/Met (p = 0.003) BDNF genotypes demonstrated a significant reduction in plasma BDNF levels over time; however, plasma BDNF levels were similar across all time points among Met homozygous carriers (p = 0.107).ConclusionThere was a statistically significant change in BDNF levels post-chemotherapy in ESBC patients, and plasma BDNF levels were associated with self-perceived concentration deficit in patients receiving chemotherapy.

Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome.

Brain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS. To compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS. This is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS. 67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p = 0.028). Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group (p = 0.04). There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p = 0.47). There was no correlation between the BDNF levels and length of hospital stay (p = 0.68) among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p = 0.045). Plasma BDNF level was significantly increased in NAS infants during the first 48 h when compared to non-NAS infants. The correlations between plasma BDNF levels and the severity of NAS warrant further study. These results suggest that BDNF may play a neuromodulatory role during withdrawal after in utero opiate exposure.

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.