Lower Brain-derived Neurotrophic Factor Research Articles

Low brain-derived neurotrophic factor and high vascular cell adhesion molecule-1 levels are associated with chronic kidney disease in patients with type 2 diabetes mellitus

BackgroundPatients with type 2 diabetes mellitus (DM) have a high prevalence of chronic kidney disease (CKD). Energy imbalance and inflammation may be involved in the pathogenesis of CKD. We examined the effects of brain-derived neurotrophic factor (BDNF) and vascular cell adhesion molecule-1 (VCAM-1) on CKD in patients with type 2 DM.MethodsPatients with type 2 DM were enrolled for this cross-sectional study. Fasting serum was prepared to measure the BDNF and VCAM-1 levels. An estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 was used as the criterion for identifying patients with CKD.ResultsOf the 548 enrolled participants, 156 had CKD. Patients with CKD exhibited significantly lower BDNF (median of 21.4 ng/mL, interquartile range [IQR]: 17.0–27.0 ng/mL vs. median of 25.9 ng/mL, IQR: 21.0–30.4 ng/mL, P <0.001) and higher VCAM-1 (median of 917 ng/mL, IQR: 761–1172 ng/mL vs. median of 669 ng/mL, IQR: 552–857 ng/mL, P <0.001) levels than those without CKD. Serum BDNF levels were inversely correlated with VCAM-1 levels (Spearman’s rank correlation coefficient = -0.210, P <0.001). The patients were divided into four subgroups based on median BDNF and VCAM-1 levels (24.88 ng/mL and 750 ng/mL, respectively). Notably, patients in the high VCAM-1 and low BDNF group had the highest prevalence (50%) of CKD. Multivariate logistic regression revealed a significantly higher odds ratio (OR) of CKD in the high VCAM-1 and low BDNF group (OR = 3.885, 95% CI: 1.766–8.547, P <0.001), followed by that in the high VCAM-1 and high BDNF group (OR = 3.099, 95% CI: 1.373–6.992, P =0.006) compared with that in the low VCAM-1 and high BDNF group. However, the risk of CKD in the low VCAM-1 and low BDNF group was not significantly different from that in the low VCAM-1 and high BDNF group (P =0.266).ConclusionCKD in patients with type 2 DM is associated with low serum BDNF and high VCAM-1 levels. BDNF and VCAM-1 have a synergistic effect on CKD. Thus, BDNF and VCAM-1 can be potential biomarkers for CKD risk stratification in patients with type 2 DM.

Investigating Neuroplasticity Changes Reflected by BDNF Levels in Astrocyte-Derived Extracellular Vesicles in Patients with Depression.

To investigate the neuroplasticity hypothesis of depression by measuring brain-derived neurotrophic factor (BDNF) levels in plasma astrocyte-derived extracellular vesicles (ADEVs) and to evaluate their potential as biomarkers for depression compared with plasma BDNF levels. Thirty-five patients with major depressive disorder (MDD) and 35 matched healthy controls (HCs) were enrolled. Plasma ADEVs were isolated using a combination of ultracentrifugation and immunoaffinity capture. Isolated ADEVs were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. BDNF levels were quantified in both ADEVs and plasma. ALG-2-interacting protein X (Alix) and cluster of differentiation 81 (CD81) levels, two established extracellular vesicle markers, were measured in ADEVs. After false discovery rate correction, patients with MDD exhibited higher CD81 levels (P FDR = 0.040) and lower BDNF levels (P FDR = 0.043) in ADEVs than HCs at baseline. BDNF levels in ADEVs normalized to CD81 (P FDR = 0.002) and Alix (P FDR = 0.040) remained consistent with this finding. Following four weeks of selective serotonin reuptake inhibitor treatment (n=10), CD81 levels in ADEVs decreased (P FDR = 0.046), while BDNF levels normalized to CD81 increased (P FDR = 0.022). BDNF levels in ADEVs were more stable than in plasma. Exploratory analysis revealed no correlation between BDNF levels in ADEVs and plasma (ρ=0.117, P = 0.334). This study provides human in vivo evidence supporting the neuroplasticity hypothesis of depression by demonstrating altered BDNF levels in ADEVs. ADEVs may be more suitable for developing biomarkers of depression than plasma-derived biomarkers.

Role of Lactobacillus plantarum-Derived Extracellular Vesicles in Regulating Alcohol Consumption.

Alcohol Use Disorder (AUD), characterized by repeated alcohol consumption and withdrawal symptoms, poses a significant public health issue. Alcohol-induced impairment of the intestinal barrier results in alterations in intestinal permeability and the composition of the intestinal microbiota. Such alterations lead to a reduced relative abundance of intestinal lactic acid bacteria. However, the role of gut microbiota in alcohol consumption is not yet fully understood. In this study, we explore the mechanism by which gut microbiota regulates alcohol consumption, specifically using extracellular vesicles derived from Lactobacillus plantarum (L-EVs). L-EVs were administered to Sprague-Dawley rats either through intraperitoneal injection or microinjection into the ventral tegmental area (VTA), resulting in a significant reduction in alcohol consumption 72 hours after withdrawal. The observed reduction was akin to the effect of an intra-VTA microinjection of Brain-Derived Neurotrophic Factor (BDNF). Intriguingly, the microinjection of K252a (a Trk B antagonist) into the VTA blocked the reducing effect of L-EVs on alcohol consumption. The intraperitoneal injection of L-EVs restored the diminished BDNF expression in the VTA of alcohol-dependent rats. Furthermore, L-EVs rescued the low BDNF expression in alcohol-incubated PC12 cells. In conclusion, our study demonstrates that L-EVs attenuated alcohol consumption by enhancing BDNF expression in alcohol-dependent rats, thus suggesting the significant therapeutic potential of L-EVs in preventing excessive alcohol consumption.

Platelet Levels of Brain-Derived Neurotrophic Factor in Adults with Autism Spectrum Disorder: Is There a Specific Association with Autism Spectrum Psychopathology?

To date, although several studies have investigated the circulating levels of brain-derived neurotrophic factor (BDNF) in children with autism spectrum disorder (ASD), only a few authors have addressed their evaluation in adults. Furthermore, an important limitation of these studies lies in the fact that circulating BDNF is stored in platelets and released into the circulation when needed. To the best of our knowledge, a very limited number of studies have related peripheral BDNF values to platelet counts, and yet no study has evaluated intra-platelet BDNF levels in adults with ASD. In this framework, the aim of the present work is to pave the way in this field and evaluate platelet BNDF levels in adult ASD patients, as well as their correlation with autistic symptoms and related psychopathological dimensions. We recruited 22 ASD and 22 healthy controls, evaluated with the Adult autism subthreshold spectrum (AdAS Spectrum), the Social Anxiety Spectrum-self report (SHY-SR), the Trauma and loss spectrum-self report (TALS-SR), the Work and Social Adjustment Scale (WSAS), and the Mood Spectrum-self report for suicidality. Intra-platelet BDNF levels were also assessed. The results highlighted lower BDNF levels in the ASD group; moreover, AdAS Spectrum and WSAS total score as well as AdAS Spectrum Restricted interest and rumination, WSAS Private leisure activities, TALS-SR Arousal, and SHY-SR Childhood domains were significant negative predictors of platelet BDNF levels.

BDNF, proBDNF and proBDNF/BDNF ratio with electroencephalographic abnormalities in children with attention deficit hyperactivity disorder: Possible relations to cognition and severity.

Attention deficit hyperactivity disorder (ADHD) with and without subclinical epileptogenic discharges (SED) have been suggested to negatively affect cognitive abilities of children with ADHD. The role of brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in ADHD is in need of being investigated. The aims were to evaluate the levels of serum BDNF, proBDNF and the proBDNF/BDNF ratio in addition to the potential impacts of SED on the children's cognitive abilities and the severity of ADHD. The included participants with ADHD were 30 children with normal electroencephalogram (EEG) (G1) and 30 children with SED (G2), together with 30 healthy children (G3). The cognitive abilities and severity of the disorder were evaluated. The biochemical measures were determined by ELISA. The presence of coexisting SED and nocturnal enuresis has led to a deleterious effect on cognitive processes but not on the severity. The focal epileptogenic discharge was the most common among children in G2. The levels of BDNF in Groups 1 and 2 were less than those in G3. The higher proBDNF/BDNF ratio could be related to the low BDNF levels rather than high proBDNF levels. The findings of this study highlight the importance of investigating the presence of SED and nocturnal enuresis in children with ADHD. Targeting strengthening of cognitive abilities in children with coexisting ADHD and SED is advised. The role of proBDNF in the pathophysiology of ADHD needs further investigation.

Exploring the Effect of Acute and Regular Physical Exercise on Circulating Brain-Derived Neurotrophic Factor Levels in Individuals with Obesity: A Comprehensive Systematic Review and Meta-Analysis.

Obesity is a major global health concern linked to cognitive impairment and neurological disorders. Circulating brain-derived neurotrophic factor (BDNF), a protein crucial for neuronal growth and survival, plays a vital role in brain function and plasticity. Notably, obese individuals tend to exhibit lower BDNF levels, potentially contributing to cognitive decline. Physical exercise offers health benefits, including improved circulating BDNF levels and cognitive function, but the specific impacts of acute versus regular exercise on circulating BDNF levels in obesity are unclear. Understanding this can guide interventions to enhance brain health and counter potential cognitive decline in obese individuals. Therefore, this study aimed to explore the impact of acute and regular physical exercise on circulating BDNF in individuals with obesity. The target population comprised individuals classified as overweight or obese, encompassing both acute and chronic protocols involving all training methods. A comprehensive search was conducted across computerized databases, including PubMed, Academic Search Complete, and Web of Science, in August 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Initially, 98 studies were identified, from which 16 studies, comprising 23 trials, met the selection criteria. Substantial heterogeneity was observed for both acute (I2 = 80.4%) and long-term effects (I2 = 88.7%), but low risk of bias for the included studies. A single session of exercise increased circulating BDNF levels among obese patients compared to the control group (ES = 1.25, 95% CI = 0.19 to 2.30, p = 0.021). However, with extended periods of physical exercise, there was no significant increase in circulating BDNF levels when compared to the control group (ES = 0.49, 95% CI = -0.08 to 1.06, p = 0.089). These findings highlight the need to consider exercise duration and type when studying neurobiological responses in obesity and exercise research. The study's results have implications for exercise prescription in obesity management and highlight the need for tailored interventions to optimize neurotrophic responses. Future research should focus on elucidating the adaptive mechanisms and exploring novel strategies to enhance BDNF modulation through exercise in this population. However, further research is needed considering limitations such as the potential age-related confounding effects due to diverse participant ages, lack of sex-specific analyses, and insufficient exploration of how specific exercise parameters (e.g., duration, intensity, type) impact circulating BDNF.

Exploring the Neurogenetic Landscape of Autism Spectrum Disorder: The Role of Brain-Derived Neurotrophic Factor (BDNF) Gene in the Complex Web of Neurodevelopment

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with varied manifestations including altered metabolic profiles. Recent research highlights the potential role of Brain-Derived Neurotrophic Factor (BDNF), a hormone derived from adipose tissue, in the pathology of ASD. BDNF levels are reportedly correlated with the severity of autism symptoms, suggesting a link between metabolic dysfunction and the disorder. Objective: This study aims to deepen the understanding of BDNF levels in individuals with ASD and to explore the implications for diagnosis, treatment, and management of the disorder. It seeks to elucidate the relationship between low BDNF levels and increased autism severity, and to identify potential therapeutic interventions targeting BDNF dysregulation. Methods: EDTA blood samples (5ml each) from 140 participants (108 with ASD and 32 healthy controls) were collected across various hospitals in Karachi. Plasma serum levels of BDNF were analyzed following a six-month follow-up. A comprehensive statistical analysis was performed, focusing on the relationship between BDNF levels and autism severity, and evaluating diagnostic and therapeutic implications of BDNF dysregulation. Results: Analysis revealed that lower BDNF serum levels were consistently associated with higher autism severity. Specifically, 60-70% of participants with ASD scored below 8 on the Mini-Mental State Examination (MMSE), indicating significant cognitive impairment. The statistical significance of these findings was confirmed with p-values <0.05. Conclusion: The study confirms that low BDNF levels are significantly associated with greater severity of autism symptoms, underscoring the importance of metabolic factors in the pathogenesis of ASD. BDNF stands out as a potential biomarker for early ASD diagnosis and personalized treatment strategies. Future Prospects: Future research should aim to delineate the mechanistic relationship between BDNF dysregulation and ASD pathology. Longitudinal studies are needed to assess the long-term effects of BDNF modulation on ASD outcomes and to validate its effectiveness as both a diagnostic and prognostic marker.

Dietary intake of methyl donor nutrients in relation to metabolic health status, serum levels of brain-derived neurotrophic factor and adropin

There is a lack of evidence on dietary intake of methyl donor nutrients with metabolic health status and related biomarkers. Thus, this study aimed to assess the relation between methyl donor nutrients intake and metabolic health status with regarding the interactive roles of brain-derived neurotrophic factor (BDNF) and adropin in Iranian adults. This cross-sectional survey was conducted among 527 Iranian adults (45.7% female) selected by multistage cluster random-sampling method. A validated food frequency questionnaire was used to evaluate participants' dietary intake. Metabolic unhealthy status was defined by Wildman criteria as having ≥ 2 of hyperglycemia, hypertriglyceridemia, hypo-HDL-cholesterolemia, hypertension, chronic inflammation, and insulin resistance. Concentrations of metabolic parameters, BDNF and adropin were determined using fasting blood samples. An inverse association was found between methyl donor nutrients intake and metabolically unhealthy status in multivariable-adjusted model (ORT3 vs. T1=0.30; 95%CI: 0.12-0.75). This association was especially significant among overweight/obese adults and was stronger in women. Additionally, consumption of vitamin B6 and choline was separately related to reduced odds of metabolically unhealthy status. Methyl donor intake was not significantly related to low BDNF (ORT3 vs. T1=0.93; 95%CI: 0.60-1.44) and adropin (ORT3 vs. T1=0.71; 95%CI: 0.44-1.15). However, the interaction between high methyl donor nutrients intake and high BDNF was related to lower odds of metabolically unhealthy status in multivariable-adjusted model (ORMDNS∗BDNF=0.27; 95%CI: 0.11-0.67). Higher intake of methyl donor nutrients, alone and in interaction with BDNF levels, was associated with decreased odds of metabolically unhealthy status in Iranian adults.

Revealing the heterogeneity of plasma protein and cognitive decline trajectory among Mild Cognitive Impairment patients by clustering of brain atrophy features

Alzheimer's disease (AD) is suggested to be a heterogeneous disorder, but limited studies explore the heterogeneity of the Mild Cognitive Impairment (MCI) stage. This study aimed to tackle such problems using the CIMLR (Cancer Integration via Multikernel Learning) algorithm to cluster brain structural features extracted from T1-weighted Magnetic Resonance Images of MCI patients from Alzheimer's Disease Neuroimaging Initiative. The demographic and cognitive results, characteristics of brain structural features, plasma biomarkers, and longitudinal cognitive trajectory were analyzed for each cluster. The CIMLR clustering analysis revealed four distinct clusters. Cluster 1 is the oldest group but has had mild atrophy and moderate progression with elevated Tumor Necrosis Factor Receptor 2 level; and low Brain-Derived Neurotrophic Factor and CD40 Ligand levels. Cluster 2 showed the highest risk for aggressive MCI progression, with abnormal Leptin, Adiponectin, and Creatine kinase-MB values. Cluster 3 exhibited a low level of Monokine Induced by Gamma Interferon and mild atrophy that shared similar patterns with Cluster 1. Cluster 4 represented the healthiest group during longitudinal tracking, with the mildest Parahippocampal atrophy, which was found to be positively correlated with cognitive impairment and amino acid levels. The longitudinal analyses showed the potential of Hepatocyte Growth Factor as a marker for slow cognitive impairment; Cortisol and Neurofilament Light Polypeptide as prognosis markers for aggressive MCI progression. These findings may lay out new suggestions for further research contributing to the accurate diagnosis and precision medicine for dementia and AD.

Stress during pregnancy and fetal serum BDNF in cord blood at birth

IntroductionAdverse environments during pregnancy impact neurodevelopment including cognitive abilities of the developing children. The mediating biological alterations are not fully understood. Maternal stress may impact the neurotrophic regulation of the offspring as early as in utero and at birth. Brain-derived neurotrophic factor (BDNF) is essential for neurodevelopment. Short-term higher levels of BDNF in mice upon stressors associate with lower BDNF later in life, which itself associates with depression in animals and humans. Stress including glucocorticoids may impact BDNF, but there is a lack of data at birth. This study investigated if stress near term associates with fetal BDNF at birth in humans. MethodsPregnant women near term who underwent primary cesarean sections (at 38.80±0.64 weeks), were included in this study (n=41). Stress at the end of pregnancy was assessed before the cesarean section by determining maternal depressive symptoms (EDPS), maternal state and trait anxiety (STAI-S and STAI-T), maternal prenatal distress (PDQ), stress over the past month (PSS), prenatal attachment to the offspring (PAI), maternal social support (F-Sozu), maternal early life stress (CTQ), socioeconomic status, and the glucocorticoids cortisol and cortisone (n=40) in amniotic fluid at birth. The association with fetal BDNF was analyzed. Cord blood serum of n=34 newborns at birth was analyzed for BDNF and newborn anthropometrics (weight, length and head circumference per gestational age at birth) were assessed. The association of fetal BDNF with anthropometrics at birth was analyzed. ResultsAfter a BDNF-outlier (>3 SD) was removed, higher fetal BDNF associated significantly with maternal depressive symptoms (r=0.398, p=0.022), with lower socioeconomic status as assessed by the average number of people per room in the household (r=0.526, p=0.002) and with borderline significance with net income per person in the household (r=-0.313, p=0.087) in the bivariate analyses. In multivariable analysis, BDNF stayed positively associated with maternal depressive symptoms (β=0.404, 95% CI [7.057, 306.041], p=0.041) and lower net income per person in the household (β=-0.562, 95% CI [-914.511, −60.523], p=0.027) when controlling for maternal age, maternal pre-pregnancy BMI, fetal sex and gestational age. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed in bivariate analyses or in multivariable analyses when controlling for maternal BMI and fetal sex. ConclusionMaternal depressive symptoms and lower socioeconomic status associated with higher fetal BDNF when controlling for confounders. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed. Further studies should investigate how early altered BDNF associate with the development and possibly psychopathology of the offspring.

Independent Impact of Brain-Derived Neurotrophic Factor on Cardiovascular Prognosis in Coronary Heart Disease Patients: A Prospective Cohort Study

Abstract Objectives: Brain-derived neurotrophic factor (BDNF) as a biomarker of depressive symptoms manifests a novel role in the cardiovascular system. This study aims to indicate the association of BDNF levels between depressive symptoms and the cardiovascular prognosis in coronary heart disease (CHD) patients. Methods: Participants were recruited from hospitalized CHD patients between November 18, 2020 and November 26, 2021, in the First Affiliated Hospital of Shantou University Medical College. Serum BDNF levels were measured by the enzyme-linked immunosorbent assays. Depressive symptom was evaluated using Patient Health Questionnaire (PHQ-9). The cardiovascular events were the endpoint outcomes across the 12-month follow-up. Kaplan–Meier curves and Cox proportional hazards regression models were used to investigate the relationship of serum BDNF levels between depressive symptom and prognosis. Results: A total of 102 CHD patients (60.6 ± 10.4 year, 76% male) were enrolled. Based on the median serum BDNF levels, the participants were grouped into those “low BDNF (≤0.65 ng/mL)” versus “high BDNF (≥0.65 ng/mL).” CHD patients with low BDNF levels had a higher prevalence of depressive symptoms (PHQ–9 ≥10) compared with high BDNF levels. Within a median 540 days of follow-up, low serum BDNF increased the risk of cardiovascular events (adjusted hazard ratio = 3.26; 95% confidence interval = 1.18–9.02, P = 0.02) after adjustment for confounding factors. Conclusions: CHD patients with low serum BDNF levels were significantly associated with an increased risk of cardiovascular events, independently of depressive symptoms.

An acute bout of resistance exercise increases BDNF in hippocampus and restores the long-term memory of insulin-resistant rats.

A sedentary lifestyle, inadequate diet, and obesity are substantial risk factors for Type 2 diabetes mellitus (T2DM) development. A major picture of T2DM is insulin resistance (IR), which causes many impairments in brain physiology, such as increased proinflammatory state and decreased brain-derived neurotrophic factor (BDNF) concentration, hence reducing cognitive function. Physical exercise is a non-pharmacological tool for managing T2DM/IR and its complications. Thus, this study investigated the effects of IR induction and the acute effects of resistance exercise (RE) on memory, neurotrophic, and inflammatory responses in the hippocampus and prefrontal cortex of insulin-resistant rats. IR was induced by a high-fat diet and fructose-rich beverage. Insulin-resistant rats performed acute resistance exercise (IR.RE; vertical ladder climb at 50-100% of the maximum load) or rest (IR.REST; 20min). Cognitive parameters were assessed by novel object recognition (NOR) tasks, and biochemical analyses were performed to assess BDNF concentrations and inflammatory profile in the hippocampus and prefrontal cortex. Insulin-resistant rats had 20% worse long-term memory (LTM) (p < 0.01) and lower BDNF concentration in the hippocampus (-14.6%; p < 0.05) when compared to non-insulin-resistant rats (CON). An acute bout of RE restored LTM (-9.7% pre vs. post; p > 0.05) and increased BDNF concentration in the hippocampus (9.1%; p < 0.05) of insulin-resistant rats compared to REST. Thus, an acute bout of RE can attenuate the adverse effects of IR on memory and neurotrophic factors in rats, representing a therapeutic tool to alleviate the IR impact on the brain.

Circulating levels of brain-derived neurotrophic factor (BDNF) in patients with bipolar disorders may be influenced by mitochondrial dysfunction, inflammation, and history of childhood trauma

BackgroundBipolar disorders are underpinned by deregulated immune processes including chronic inflammation. The crosstalk between immune factors and homeostatic molecules remains scarcely studied. The brain-derived neurotrophic factor is a neurotrophic molecule essential for neuronal and synaptic homeostasis. We explored correlations between BDNF levels and factors known to contribute to sustained inflammation, namely mitochondrial dysfunction (mtDNAcn), inflammation, and history of childhood maltreatment (CM). Methods175 patients with BD assessed either during acute mood episode or when euthymic and 85 healthy controls were included. CM history was assessed by the Childhood Trauma Questionnaire. Circulating levels of inflammatory molecules, BDNF and mitochondrial DNA copy number were determined. Correlations between the studied parameters were analyzed. ResultsLow levels of BDNF were observed during acute mood episodes (mania/mixed/depression). We observed that IL-12/23p40 levels and history of CM were negatively correlated with circulating BDNF levels in acutely ill patients. In euthymic patients we found that while TNFα levels correlate negatively with BDNF levels, that of IL16, VEGF and mtDNAcn were positively correlated. Linear regression showed that: (i) in the whole BD sample, low mtDNAcn levels were associated with low BDNF levels (ii) in acutely ill BD patients, high CTQ-AE scores, and high IL-12/23p40 levels were associated with low BDNF levels. (ⅲ) in euthymic BD patients, low mtDNAcn levels were associated with low BDNF levels. LimitationsWe acknowledge the relatively low sample size. ConclusionsWe identified some of the immune factors possibly influencing the levels of BDNF. Future studies involving larger cohorts are warranted.

Low serum brain-derived neurotrophic factor may predict poor response to cardiac rehabilitation in patients with cardiovascular disease.

It has been shown that serum brain-derived neurotrophic factor (BDNF) is associated with skeletal muscle energy metabolism and that BDNF is a predictor of mortality in heart failure patients. However, little is known about the relationship between BDNF and cardiac rehabilitation (CR). Therefore, this study retrospectively investigated the effects of baseline serum BDNF levels on the CR-induced exercise capacity improvement in patients with cardiovascular disease (CVD). We assigned 99 CVD patients (mean age 71±12 years, male = 60) to Low, Middle, and High groups based on the tertiles of baseline BDNF levels. Cardiopulmonary exercise testing was done using supervised bicycle ergometer twice before and after 3 weeks of CR. Analysis of covariance (ANCOVA) followed by post-hoc analysis using Tukey's HSD test was conducted to assess the multivariate associations between baseline BDNF levels categorized by BDNF tertiles (as independent variable) and %increases in AT and peak VO2 after 3-week CR (as dependent variables) after adjustment for age and gender (as covariates), as a main statistical analysis of the present study. The higher the baseline BDNF levels, the better nutritional status evaluated by the CONUT score (p<0.0001). Baseline anaerobic threshold (AT) and peak oxygen uptake (peak VO2) were similar among the three groups. ANCOVA followed by post-hoc analysis revealed that age- and gender-adjusted %increases in peak VO2 after 3-week CR were positively associated with baseline BDNF levels (p = 0.0239) and Low BDNF group showed significantly lower %increase in peak VO2 than High BDNF group (p = 0.0197). Significant association was not found between baseline BDNF and %increase in AT (p = 0.1379). Low baseline BDNF levels were associated with malnutrition in CVD patients. A positive association between baseline BDNF levels and CR-induced increases in peak VO2 was found. It was suggested that CVD patients with low baseline BDNF levels may be poor responders to CR.

Peripheral Levels of the Brain-Derived Neurotrophic Factor in Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Among its functions, brain-derived neurotrophic factor (BDNF) regulates endothelial and macrophage activation, possibly playing a role in atherosclerotic plaque pathophysiology. Given contradicting reports, this study sought to investigate whether blood levels of BDNF differed between patients with coronary heart disease (CHD) and controls. We explored PubMed, Embase, Web of Science, and Cochrane Library for studies comparing BDNF blood levels in patients with CHD and controls. Random-effect meta-analysis was conducted to calculate the standardized mean differences (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa scale was used to evaluate the quality of included articles, and statistical analyses were conducted using R version 4.0.4. The final analysis comprised 12 investigations covering 1422 CHD cases and 929 controls with mean ages of 59.66±13.56 and 53.78±13.61 years, respectively. The initial analyses revealed a tendency toward low levels of BDNF in the CHD group compared with the control group (SMD= -0.41; 95% CI, -1.12 to 0.30; P=0.26). After the removal of outliers, the difference achieved statistical difference (SMD= -0.56; 95% CI, -0.93 to -0.19; P<0.01). Subgroup analysis demonstrated no significant difference between serum and plasma BDNF levels (P=0.54); however, subgroup analyses of studies investigating plasma BDNF showed that patients with CHD had significantly lower BDNF levels. Serum and plasma BDNF concentrations were considerably lower in patients with CHD than in healthy controls. Further studies of higher quality are required on the potential role of BDNF as a biomarker of CHD pathophysiology and severity.

Mild repetitive TBI reduces brain-derived neurotrophic factor (BDNF) in the substantia nigra and hippocampus: A preclinical model for testing BDNF-targeted therapeutics

Clinical studies have consistently shown that neurodegenerative diseases (NDs) such as Parkinson's disease, Alzheimer's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease show absent or low levels of brain-derived neurotrophic factor (BDNF). Despite this relationship between BDNF and ND, only a few ND animal models have been able to recapitulate the low BDNF state, thereby hindering research into the therapeutic targeting of this important neurotrophic factor. In order to address this unmet need, we sought to develop a reproducible model of BDNF reduction by inducing traumatic brain injury (TBI) using a closed head momentum exchange injury model in mature 9-month-old male and female rats. Head impacts were repetitive and varied in intensity from mild to severe. BDNF levels, as assessed by ELISA, were significantly reduced in the hippocampus of both males and females as well as in the substantia nigra of males 12 days after mild TBI. However, we observed significant sexual dimorphism in multiple sequelae, including magnetic resonance imaging-determined vasogenic edema, astrogliosis (GFAP-activation), and microgliosis (Iba1 activation). This study provides an opportunity to investigate the mechanism of BDNF reduction in rodent models and provides a reliable paradigm to test BDNF-targeted therapeutics for the treatment of ND.

Adherence to Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay Diet in Relation to Serum Brain-Derived Neurotrophic Factor Concentrations and Metabolic Health Status in Adults

BackgroundThere is a lack of data regarding the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet and metabolic health. ObjectivesThis study assessed the relation between MIND diet and metabolic health status relative to serum brain-derived neurotrophic factor (BDNF) concentrations. MethodsThis was a cross-sectional study of 527 adults (286 males and 241 females) recruited from 20 schools in 6 different educational districts of Isfahan, Iran. Dietary intakes of participants were collected by a validated 168-item food frequency questionnaire, and MIND diet score was estimated. Anthropometric indices, blood pressure, biochemical parameters, and BDNF concentrations were assessed for all participants. The metabolically unhealthy (MU) phenotype was determined based on blood pressure, glycemic and lipid profiles, chronic inflammation, and insulin resistance. ResultsThe frequency of MU phenotype among obese/overweight and normal-weight individuals was 79.5 % and 20.5 %, respectively. After adjustment for confounders, individuals in the top tertile of the MIND diet scores had 58 % lower odds of having the MU phenotype than individuals in the bottom tertile (odds ratios [ORs]: 0.42; 95 % confidence interval [CI]: 0.20, 0.90). In the fully adjusted model, females and normal-weight individuals had 81 % (OR: 0.19; 95 % CI: 0.04, 0.83) and 89 % (OR: 0.11; 95 % CI: 0.02, 0.69) lower chance of developing the MU phenotype, respectively. In addition, significant inverse associations between adherence to the MIND diet and high-blood pressure and hypertriglyceridemia were found. No significant association was found between adherence to MIND diet and odds of low BDNF concentrations. ConclusionsAdherence to MIND diet is inversely associated with odds of MU phenotype, especially among women and normal-weight individuals. BDNF concentration is not associated with MIND diet and MU status.

BDNF Signaling in Vascular Dementia and Its Effects on Cerebrovascular Dysfunction, Synaptic Plasticity, and Cholinergic System Abnormality.

Vascular dementia (VaD) is the second most common type of dementia and is characterized by memory impairment, blood-brain barrier disruption, neuronal cell loss, glia activation, impaired synaptic plasticity, and cholinergic system abnormalities. To effectively prevent and treat VaD a good understanding of the mechanisms underlying its neuropathology is needed. Brain-derived neurotrophic factor (BDNF) is an important neurotrophic factor with multiple functions in the systemic circulation and the central nervous system and is known to regulate neuronal cell survival, synaptic formation, glia activation, and cognitive decline. Recent studies indicate that when compared with normal subjects, patients with VaD have low serum BDNF levels and that BDNF deficiency in the serum and cerebrospinal fluid is an important indicator of VaD. Here, we review current knowledge on the role of BDNF signaling in the pathology of VaD, such as cerebrovascular dysfunction, synaptic dysfunction, and cholinergic system impairment.

Peripheral blood diagnostic markers of chronic cerebral hypoperfusion.

To investigate the efficacy of ischemia-modified albumin (IMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), brain-derived neurotrophic factor (BDNF), and visinin-like protein-1 (VILIP-1) in diagnosing chronic cerebral hypoperfusion (CCH). This retrospective study included 84 patients with suspected chronic cerebral ischemia admitted to Sichuan Provincial People's Hospital between February 2021 and April 2022. Arterial spin labeling (ASL) imaging and biological examinations were performed. According to the ASL perfusion imaging patterns, the patients were divided into a CCH group (n = 55) and a non-CCH group (n = 29). Serum markers of the two groups were compared, and correlation analysis was conducted between ischemic marker levels and cerebral blood flow (CBF) in the ischemic region, as measured by ASL. Receiver operating characteristic (ROC) curve analysis was used to evaluate the efficacy of each marker for diagnosing chronic cerebral ischemia. The Delong test was used to compare AUC size between groups. Compared to the non-CCH group, the CCH group exhibited higher IMA levels and lower BDNF concentrations (P < 0.05). However, VILIP-1 and Lp-PLA2 concentrations were not significantly different between the two groups (P > 0.05). Moreover, IMA and BDNF levels were not correlated with CBF in the hypoperfused area. ROC curve analysis demonstrated that the cut-off values of 24.2915 U/mL and 6.714 ng/L for IMA and BDNF achieved a sensitivity of 83.6% and 41.8% and a specificity of 62.1% and 93.1%, respectively. Lastly, the areas under the curve for IMA and BDNF were 0.738 (95% confidence interval [CI], 0.627-0.848) and 0.631 (95% CI, 0.512-0.751), respectively. IMA and BDNF may have clinical value in the diagnosis of CCH.

Neurodegeneration in diabetic retinopathy: An insight on its main signalling pathways

Aims/Purpose: In the latest years neurodegeneration has been considered as one of the main pathological processes involved in proliferative diabetic retinopathy's (PDR) onset and progression. We aimed to increase the understanding on the role of the main signalling molecules that participate in this phenomenon, including apoptotic, excitotoxic and neurotrophic factor pathways.Methods: Participants of both sexes were selected and programmed for vitrectomy by its diabetes mellitus 2 (DM2)‐derived vitreoretinal complications (PDR group, PDRG; n = 20), or by suffering macular hole, epiretinal membrane or rhegmatogenous retinal detachment (as the surrogate control group, SCG; n = 26). Vitreous body (VIT) and plasma (PLS) samples were collected and processed to determine the glutamate, caspase‐3 (CAS‐3) and brain‐derived neurotrophic factor (BDNF) levels. Next‐Generation Sequencing (NGS) techniques were applied to characterize the miRNA expression pattern in both groups.Results: Significantly higher VIT glutamate (p &lt; 0.05) and CAS‐3 (p &lt; 0.05), and significantly lower BDNF (p &lt; 0.05) levels were detected in the PDRG. Significantly higher PLS glutamate (p &lt; 0.05) and CAS‐3 (p &lt; 0.05) levels were found in diabetics. However, PLS levels of BDNF showed no differences between groups (p = 0.80). NGS analysis showed a different miRNA expression pattern between both groups.Conclusions: Diabetes‐induced changes in retinal neurons/glia may be the key to discover preclinical biomarkers for better managing diabetic eyes. Glutamate, caspase‐3 and BDNF, playing important roles in the neurodegenerative processes occurring in PDR, are pivotal candidates to identify diabetics at high risk of sight‐threatening complications. Additionally, certain miRNAs could be playing an important role in these signalling pathways, being involved in PDR's neurodegenerative phenomenon.