Brain-derived Neurotrophic Factor Concentrations Research Articles

Maternal organokines throughout pregnancy as predictors of neonatal anthropometric characteristics and adiposity

AimsTo evaluate the relation between maternal concentrations of progranulin (PGRN), adipocyte fatty acid-binding protein (AFABP), brain-derived neurotrophic factor (BDNF), and fibroblast growth factor 21 (FGF21) throughout pregnancy with neonatal weight and length at birth and at one month of age, as well as with the percentage of fat mass at one month of age. Besides, we evaluated the association between maternal organokine concentrations with pregestational nutritional status and gestational weight gain (GWG).MethodsLongitudinal study of 100 healthy pregnant women and their neonates. Conventional biochemical tests were performed and maternal organokine concentrations were measured by ELISA. Neonatal percent fat mass was determined using the PEA POD system, and weight and length were measured using a soft tape measure and a baby scale. Multiple linear regression models were made to predict neonatal anthropometric measurements and adiposity.ResultsIn all women, PGRN concentrations significantly increased as pregnancy progressed, while AFABP concentrations increased until the third trimester and the highest BDNF concentrations were observed in the second trimester of pregnancy. In contrast, FGF21 concentrations did not change during pregnancy. Only maternal obesity was associated with some differences in AFABP and FGF21 concentrations. Gestational age at birth, maternal age and third-trimester PGRN concentrations predicted weight (gestational age at birth: β=0.11; maternal age: β=-0.033; PGRN: β=0.003, p<0.001) and, together with first-trimester BDNF concentrations, length (gestational age at birth: β=0.76; maternal age: β=-0.21; PGRN: β=0.24; BDNF: β=0.06, p<0.001) at birth. Maternal age and third-trimester BDNF concentrations predicted one-month-old neonate length (maternal age: β=-1.03; BDNF: β=0.45, p<0.001). Pregestational body mass index (pBMI), GWG, second-trimester FGF21 concentrations, and third-trimester AFABP concentrations predicted neonatal fat mass percentage (pBMI: β=-0.58; GWG: β=-0.32; FGF21: β=-0.004; AFABP: β=-1.27, p<0.001) at one month of age.ConclusionMaternal PGRN, AFABP, and BDNF concentrations, but not FGF21, vary throughout pregnancy. These organokines and maternal characteristics can be useful in the prediction of neonatal weight, length, and percentage fat mass.

Bedtime banana and milk intake on sleep and biochemical parameters.

This study aimed to evaluate the effects of milk and banana given as a bedtime snack to patients with primary insomnia on sleep parameters and some biochemical parameters such as brain-derived neurotrophic factor, leptin, and ghrelin. 21 patients with insomnia who met the inclusion criteria participated in this study. The patients were divided into 3 parallel groups: banana, milk and control. The intervention group were given either 1 portion of banana or just 200 mL of whole-fat milk at bedtime. The control group did not consume any non-routine food. Venous blood samples were taken at baseline and after the study from patients to measure brain-derived neurotrophic factor, leptin and ghrelin concentrations. Sleep quality and architecture were determined by polysomnography and Pittsburg Sleep Quality Index. Pittsburg Sleep Quality Index scores of the banana and milk group were found to be lower after intervention (p<0.05). In terms of polysomnography, the total sleep time of the milk group was found to be significantly higher than baseline. Serum ghrelin concentration of the milk group decreased significantly compared to baseline. Bedtime milk or banana intake was effective in dealing with insomnia. Foods rich in tryptophan, such as banana and milk, given at bedtime, may improve sleep parameters and appetite hormones.

Effect of He's qiangtong method of acupuncture on serological levels in patients with acute ischaemic stroke

To investigate the repair effects of He's qiangtong method of acupuncture (involved bloodletting technique with strong action of unblocking) on the neurovascular unit of the patients with acute ischemic stroke (AIS) in terms of serological indicators so as to provide new ideas for the treatment of AIS. Seventy subjects with AIS were randomly divided into an observation group (35 cases, 1 case dropped out) and a control group (35 cases , 4 cases dropped out). Patients in the control group were treated with conventional regimen. In the observation group, the bloodletting was operated, combined with the conventional treatment. Bloodletting was performed at Baihui (GV20), Sishencong (EX-HN1) and bilateral Erjian (EX-HN6), using He's qiangtong method of acupuncture, 3 times a week and for 2 weeks. Before and after treatment, the scores of the national institute of health stroke scale (NIHSS), the modified Rankin scale (MRS), and the Barthel index were evaluated；and the serological levels of the serum brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and blood-brain barrier permeability-associated protein (S100β protein) were detected in the two groups. After treatment, NIHSS score and MRS score were decreased (P<0.01), and Barthel score was increased (P<0.01) in both groups. NIHSS score of the observation group was lower than that of the control group (P<0.01). Compared with those before treatment, the content of BDNF in both groups increased (P<0.05), and VEGF content was elevated in the observation group (P<0.05) after treatment. The total effective rate was 100% (34/34) in the observation group, higher than that (67.74%, 21/31) in the control group (P<0.01). He's qiangtong method of acupuncture can promote the recovery of neurological deficits in AIS patients and effectively improve their motor function and the activity of daily living, which may be related to the reconstruction of neurovascular unit in the brain of AIS patients by increasing the levels of serological repair factors.

Association Between the Enriched Environment Level and Serum Brain-Derived Neurotrophic Factor (BDNF) in Patients with Major Depressive Disorder.

To determine the relationship between the level of EE and serum BDNF in participants with MDD and healthy controls. Participants with MDD without antidepressant treatment and healthy controls were recruited, and their EE level and serum BDNF concentration were determined looking for correlations between their clinical characteristics and the cognitive, social, and physical activities according to the EEI. A total of 25 participants were recruited, of which 6 participants with MDD and the same number of controls were selected in a paired manner. Although no differences were found in the concentration of BDNF between the groups, positive correlations were observed between cognitive EE and BDNF (r = 0.62, p = 0.035), as well as negative social EE and the Hamilton Depression Rating Scale (HDRS) (r = -0.86, p = 0.001). The sum between cognitive and social EE showed a positive correlation with the serum concentration of BDNF (r = 0.34, p = 0.0451). The level of EE is potentially modulating the presence and severity of MDD at a clinical level, but it can also influence at a neuroplastic level through promoting or limiting the concentration of BDNF.

Preclinical safety and efficacy evaluation of the intrathecal transplantation of GMP-grade human umbilical cord mesenchymal stem cells for ischemic stroke.

Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke, but its safety, effectiveness, and mechanism remain to be elucidated. In this study, good manufacturing practice-grade human umbilical cord mesenchymal stem cells (5 × 105 and 1 × 106 cells) and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats. The results showed (1) no significant difference in mortality or general conditions among the three groups. There was no abnormal differentiation or tumor formation in various organs of rats in any group. (2) Compared with saline-treated animals, those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume, with no significant differences between different human umbilical cord mesenchymal stem cell doses. (3) Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up, and the number of positive cells significantly decreased over time. (4) Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group, while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased. (5) Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+ microvessels and doublecortin-positive cells after ischemic stroke. Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+. (6) At 14 days after intrathecal administration, brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day. Taken together, these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats. The mechanisms may include alleviating the local inflammatory response in the peri-infarct region, promoting neurogenesis and angiogenesis, and enhancing the production of neurotrophic factors.

Effects of variation in exercise training load on cognitive performances and neurotrophic biomarkers in patients with coronary artery disease.

This study compared the effects of linear (LP) and nonlinear (NLP) training periodization on cognitive functions, neurotrophic biomarkers [plasma brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)], and cathepsin-B in patients with coronary artery disease (CAD). Forty-four patients with CAD reported to our laboratory on two occasions to undergo testing procedures before and after training sessions, and were then blindly randomized to NLP or LP for 36 training sessions. Visit 1 included blood samples and a maximal cardiopulmonary exercise testing to get maximal oxygen uptake (V̇o2peak). Visit 2 included cognitive functions assessment. Thirty-nine patients completed the study (LP: n = 20, NLP: n = 19), with no observed changes in cognitive performances after the training intervention in either group. IGF-1 concentration decreased in both groups (time-effect: P < 0.001), whereas BDNF concentration increased (time-effect: P < 0.05) without group interaction, and cathepsin-B did not change after the intervention. Associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.18, P = 0.04), and ΔIGF-1 and Δshort-term/working memory (R2 = 0.17, P = 0.01) in the pooled sample, with ΔIGF-1 and ΔBDNF accounting for 10% of the variance in Δshort-term/working memory. In the LP group, associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.45, P = 0.02), ΔBDNF and Δshort-term/working memory (R2 = 0.62, P = 0.004), ΔIGF-1 and Δshort-term/working memory (R2 = 0.31, P = 0.01), and ΔIGF-1 and Δexecutive function (R2 = 0.22, P = 0.04). This study indicates that linear and nonlinear training periodization led to an increase in BDNF, and a decrease in IGF-1, without change in cognitive function in individuals with stable CAD.NEW & NOTEWORTHY We used a novel and supervised iso-energetic training, integrating both moderate- and high-intensity aerobic exercises. Our findings indicate that greater variation in training load did not yield cognitive enhancements, although both protocols exhibited positive effects on brain-derived neurotrophic factor (BDNF) levels. Moreover, this study establishes a clear positive association between short-term and working memory and neurotrophic biomarkers. In addition, the independent predictive value of change in insulin-like growth factor-1 (IGF-1) on improvement in short-term and working memory highlight the close relationship between neurotrophic markers and cognition. Consequently, our results advocate for exercise training interventions targeting neurotrophic biomarkers to enhance cognitive function among individuals with coronary artery disease.

Effect of a 12-Week High Intensity Interval Training on Serum Brain Derived Neurotrophic Factor of Obese Undergraduates

The study investigated the effect of a 12-week High Intensity Interval Training (HIIT) on Serum Brain Derived Neurotrophic Factor (BDNF) among obese undergraduates of the University of Benin. The pretest-posttest randomized experimental design was employed for the study. The study involved a population of one hundred and twenty obese undergraduates, with a sample of twenty-four selected using simple random sampling. The participants’ anthropometric profiles were analyzed descriptively using mean and standard deviation, and the hypothesis was tested using analysis of covariance (ANCOVA) with statistical significance set at a p-value of &lt;0.05. The Bonferroni post-hoc test was conducted to pinpoint the source of the differences between the groups. The results showed a significantly higher increase in Serum BDNF levels (2.07 ± 1.9 vs. 2.38 ± 2.1) in the experimental group. This suggests that the HIIT protocol had a notable impact on the serum BDNF concentration of the obese undergraduates. Therefore, HIIT may serve as an effective intervention for elevating BDNF levels and potentially enhancing brain health. The study recommends that policymakers in Nigeria and other sub-Saharan African nations should prioritize addressing obesity due to its potential cognitive complications.

Вміст гамма-аміномасляної кислоти та мозкоспецифічного нейротрофічного фактора в структурах головного мозку щурів із алкогольною залежністю та після фізичних навантажень

The state of alcohol dependence is usually accompanied by emotional disorders, such as anxiety, depression, and aggressiveness. They arise against the background of disturbances in central neurotransmission and neurotrophic processes. Exercise is effective in restoring some damaged brain functions. The aim of our work was to identify disturbances in the g-aminobutyric acid (GABA) and brain-derived neurotrophic factor (BDNF) regulatory systems and the possibilities of their correction by exercise in rats with alcohol dependence. Alcohol dependence was modeled by ingesting food with alcohol at a dose of 1.25 g per kg body weight for 30 days, followed by alcohol withdrawal for 10 days. In rats under alcohol withdrawal, we found an imbalance of GABAergic activity between the frontal neocortex, hippocampus, and amygdala, a decrease in BDNF concentrations in the frontal neocortex, hippocampus, and serum, accompanied by increased anxiety levels. Wheel running during alcohol withdrawal (30 min daily for 10 days) restored the balance of GABA content in the brain structures and the reduced levels of BDNF (excluding reduced GABA and BDNF content in the frontal neocortex), and also reduced anxiety. Exercise increased hippocampal weight, which was decreased in alcohol-dependent animals. The negative correlation was found between indices of hippocampal weight and GABA concentration in hippocampus in intact and alcohol-dependent animals, which persisted even after exercise. The findings suggest that exercise is effective in restoring GABAergic and BDNF signaling impaired by alcohol intake. Restoration of synchronizing GABAergic regulation and BDNF levels contributes to anxiety reduction in alcohol-dependent rats

Ultra-processed foods intake in relation to metabolic health status, serum brain-derived neurotrophic factor and adropin levels in adults

BackgroundIn recent years, there has been a lot of discussion over the impact of ultra-processed foods (UPFs) intake on overall health of subjects. However, the association between UPFs intake and metabolic unhealthy (MU) status is still in a state of ambiguity. The current study assessed the relationship between UPFs intake and MU status with regard to brain-derived neurotrophic factor (BDNF) and adropin levels.MethodsA sample of Iranian adults (aged 20–65 years) was selected to participate in this cross-sectional study using a multistage cluster random-sampling method. UPFs intake was assessed by a validated food frequency questionnaire and NOVA classification. Concentrations of metabolic parameters, BDNF and adropin were determined through fasting blood samples. MU status was assessed according to the criteria proposed by Wildman.ResultsThe overall prevalence of MU phenotype among study participants (n = 527) was 42.5%. Higher intake of UPFs was associated with elevated odds of MU status in multivariable-adjusted model (ORT3 vs. T1=1.88; 95%CI: 1.02–3.45). Moreover, a positive association was observed between UPFs intake and hypertriglyceridemia after controlling all confounders (ORT3 vs. T1=2.07; 95%CI: 1.15–3.73). However, each tertile increase in UPFs intake was not significantly associated with serum BDNF (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\beta\\:$$\\end{document}=0.15; 95%CI: -0.05, 0.34; P = 0.14) and adropin (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\beta\\:$$\\end{document}=-1.37; 95%CI: -6.16, 3.42; P = 0.58) levels in multivariable-adjusted linear regression models.ConclusionOur findings suggested that higher consumption of UPFs was related to increased likelihood of MU status among a sample of Iranian adults. Further longitudinal studies are needed to verify the directionality and generalizability of the results to all adult populations.

Assessment of brain-derived neurotrophic factor and irisin concentration in children with chronic kidney disease: a pilot study

Patients suffering from chronic kidney disease (CKD) are particularly placed at risk of multiorgan complications. One of them is malnutrition, which adds up to a higher mortality factor among them. This study was designed to determine the usefulness of brain-derived neurotrophic factor (BDNF) and irisin assays in the assessment of CKD development. The study group included 28 children with CKD at stages 2-5 treated conservatively. The outcome of our study revealed decreased serum BDNF and irisin levels in CKD patients, whereas urine concentrations were increased for BDNF and decreased for irisin, comparing to healthy controls. There was a positive correlation between anthropometric measures and urine BDNF concentration, as well as anthropometric measures and both serum and urine irisin levels in the study group, however no dependence of the tested markers on the stage of CKD was observed. In recent years, a role of myokines was described as vital for maintaining metabolic homeostasis therefore we suspect a potential role of these multifaceted markers in detecting malnutrition in CKD children.

Sport technology in combination with neural guidance channels loaded with Inula helenium extract for peripheral nervous system repair

The peripheral nervous system (PNS) consists of nerves that extend beyond the brain and spinal cord, connecting the body to the central nervous system (CNS). Peripheral nerve injuries, caused by trauma, compression, or disease, often result in sensory and motor deficits. In the current study, a nanofibrous neural conduit was developed by loading Inula helenium extract into electrospun PCL/gelatin scaffolds. Then, the scaffolds were characterized in vitro using different analysis methods. Then, the electrospun sheets were rolled up to produce neural conduits. Finally, the healing efficacy of the developed system was investigated in a rat model of sciatic nerve injury. Results showed that the animals that were treated with both treadmill exercise and the Inula helenium extract-loaded conduits had significantly better functional recovery and histopathological recovery. ELISA assay showed that the hybrid treatment method increased tissue concentrations of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) and decreased tumor necrosis factor- α (TNF- α) tissue levels.

Neuroinflammatory Biomarkers and Their Associations With Cognitive, Affective, and Functional Outcomes 3 to 12 Months After a Traumatic Brain Injury: A Pilot Study.

Neuroinflammation is an important feature of traumatic brain injury (TBI) that remains poorly understood in the 3- to 12-month period post-TBI. The purpose of our pilot study was to examine the relationships between biomarkers of neuroinflammation and functional outcomes in TBI patients 3 to 12months postinjury. TBI patients (n =36) 3 to 12months post-TBI were recruited from a South Florida TBI clinic from May 2022 to June 2023. The Disability Rating Scale, Satisfaction with Life Scale, NIH Toolbox Sorting Working Memory, Neuro-Quality of Life Cognitive Function, Anxiety, Depression, and Sleep assessments were performed. Multiple plasma biomarkers were assayed. Analysis of variance was used to compare between-group results. Linear regression was performed to analyze relationships between biomarkers and outcomes. Brain-derived neurotrophic factor concentrations were higher as postinjury time interval increased and were associated with cognitive battery outcomes. S-100β and glial fibrillary acidic protein were associated with anxiety score and hospital length of stay; S-100β was also associated with depression. Interleukin 6 was associated with cognitive function score and time since injury. We found S-100β, glial fibrillary acidic protein, Interleukin 6, and brain-derived neurotrophic factor to play a larger role in the TBI recovery period than other biomarkers examined. Clinicians should continue to monitor for symptoms post-TBI, as the neuroinflammatory process continues to persist even into the later rehabilitation stage.

Associations between Urinary Phthalate Metabolites with BDNF and Behavioral Function among European Children from Five HBM4EU Aligned Studies.

Based on toxicological evidence, children's exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6-12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children's total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS-IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: -8.8%; 95% CI: -16.7, -0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children's exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a "urine concentration bias" that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations.

Increased Salivary BDNF and Improved Fundamental Motor Skills in Children Following a 3-Month Integrated Neuromuscular Training in Primary School.

Brain-derived neurotrophic factor (BDNF) is a protein involved in synaptic transmission and neuronal plasticity, which underlie the processes of learning and memory formation. Acute exercise and exercise training increase BDNF concentration. We aimed to evaluate the effects of a 3-month integrated neuromuscular training (INT) on salivary BDNF concentration and the mastery of fundamental motor skills in school-aged children. An additional goal was to explore the associations between potential changes in BDNF and fundamental motor skills. Sixty-seven primary school-aged children were randomly allocated to control (N = 32; 7.52 ± 0.31 y) or INT groups (N = 35; 7.56 ± 0.29 y). A 3-month INT was applied during the warm-up of physical education (PE) classes, twice weekly. Salivary BDNF was measured using a sandwich-enzyme-linked immunosorbent assay and the mastery of fundamental motor skills was assessed using the CAMSA test, at baseline and after 3 months. The children in the INT group, as compared to the children in the control group, exhibited higher salivary BDNF (F = 8.865; p = 0.004), higher scores for sidestep (F = 13.240, p = 0.001), 1-foot hop (F = 11.684, p = 0.001), kick (F = 4.010, p = 0.050), the sum of locomotor skills (F = 18.799, p < 0.0001), and the sum of control and manipulative skills (F = 8.151, p = 0.006), as well as the total sum of fundamental motor skills (F = 11.266, p = 0.001) after the 3 months. Interestingly, the increase in salivary BDNF concentration after the 3-month INT was associated with an improvement in locomotor skills (beta = 0.385; p = 0.039; adjusted R2 = 0.088) and the total improvement in fundamental motor skills (beta = 0.428; p = 0.020; adjusted R2 = 0.124). A school-based 3-month INT increased salivary BDNF and improved the mastery of fundamental motor skills in children, highlighting the positive impact of this intervention for a pediatric population.

Circadian rhythm of brain-derived neurotrophic factor in serum and plasma.

The neurotrophic growth factor brain-derived neurotrophic factor (BDNF) plays a crucial role in various neurodegenerative and psychiatric diseases, such as Alzheimer's disease, schizophrenia and depression. BDNF has been proposed as a potential biomarker for diagnosis, prognosis and monitoring therapy. Understanding the factors influencing BDNF levels and whether they follow a circadian rhythm is essential for interpreting fluctuations in BDNF measurements. We aimed to investigate the circadian rhythm of BDNF by collecting multiple peripheral venous blood samples from young, healthy male participants at 12 different time points over 24h. In addition, vital parameters, cortisol and insulin like growth factor 1 (IGF1) were measured to explore potential regulatory mechanisms, interfering variables and their correlations with BDNF concentration. The findings revealed that plasma BDNF did not exhibit any significant fluctuations over 24h, suggesting the absence of a circadian rhythm. However, serum BDNF levels decreased during sleep. Furthermore, serum BDNF showed a positive correlation with heart rate but a negative correlation with IGF1. No significant correlation was observed between cortisol and BDNF or IGF1. Although plasma BDNF suggests steady-state conditions, the decline of serum BDNF during the nocturnal period could be attributed to physical inactivity and associated with reduced haemodynamic blood flow (heart rate reduction during sleep). The type of sample collection (peripheral venous cannula vs. blood sampling using a butterfly system) does not significantly affect the measured BDNF levels. The sample collection during the day did not significantly affect BDNF analysis, emphasizing the importance of considering activity levels rather than timing when designing standardized protocols for BDNF assessments.

The effect of salidroside in promoting endogenous neural regeneration after cerebral ischemia/reperfusion involves notch signaling pathway and neurotrophic factors

BackgroundSalidroside is the major bioactive and pharmacological active substance in Rhodiola rosea L. It has been reported to have neuroprotective effects on cerebral ischemia/reperfusion (I/R). However, whether salidroside can enhance neural regeneration after cerebral I/R is still unknown. This study investigated the effects of salidroside on the endogenous neural regeneration after cerebral I/R and the related mechanism.MethodsFocal cerebral I/R was induced in rats by transient middle cerebral artery occlusion/reperfusion (MCAO/R). The rats were intraperitoneally treated salidroside once daily for 7 consecutive days. Neurobehavioral assessments were performed at 3 days and 7 days after the injury. TTC staining was performed to assess cerebral infarct volume. To evaluate the survival of neurons, immunohistochemical staining of Neuronal Nuclei (NeuN) in the ischemic hemisphere were conducted. Also, immunofluorescence double or triple staining of the biomarkers of proliferating neural progenitor cells in Subventricular Zone (SVZ) and striatum of the ischemia hemisphere were performed to investigate the neurogenesis. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of neurotrophic factors (NTFs) brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Expression of Notch1 and its target molecular Hes1 were also analyzed by western-blotting and RT-PCR.ResultsSalidroside treatment ameliorated I/R induced neurobehavioral impairment, and reduced infarct volume. Salidroside also restored NeuN positive cells loss after I/R injury. Cerebral I/R injury significantly increased the expression of 5-Bromo-2’-Deoxyuridine (BrdU) and doublecotin (DCX), elevated the number of BrdU/Nestin/DCX triple-labeled cells in SVZ, and BrdU/Nestin/glial fibrillary acidic protein (GFAP) triple-labeled cells in striatum. Salidroside treatment further promoted the proliferation of BrdU/DCX labeled neuroblasts and BrdU/Nestin/GFAP labeled reactive astrocytes. Furthermore, salidroside elevated the mRNA expression and protein concentration of BDNF and NGF in ischemia periphery area, as well. Mechanistically, salidroside elevated Notch1/Hes1 mRNA expression in SVZ. The protein levels of them were also increased after salidroside administration.ConclusionsSalidroside enhances the endogenous neural regeneration after cerebral I/R. The mechanism of the effect may involve the regulation of BDNF/NGF and Notch signaling pathway.

A novel probiotic formula, BLLL, ameliorates chronic stress-induced depression-like behaviors in mice by reducing neuroinflammation and increasing neurotrophic factors.

Introduction: Probiotics have been recognized for their various biological activities, including antioxidant and anti-inflammatory properties. This study investigates the therapeutic effect of a novel probiotic formula, BLLL, consisting of Bifidobacterium breve, Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus helveticus, on chronic stress-induced depression-like behaviors in mice. Methods: The BLLL formula or phosphate-buffered saline (PBS) was given orally at a dose of 2, 4, or 8 × 1010 CFU/kg once daily for 10days in mice treated with chronic unpredictable stress (CUS) treated or vehicle. Depression-like behaviors were assessed using the sucrose preference test (SPT), the forced swimming test (FST), and the tail suspension test (TST). The mRNA and/or protein expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), IL-4, IL-10, and chitinase-3-like protein 3 (CHI3L1, also known as Ym-1), as well as the concentration of nitrite, malondialdehyde (MDA), glutathione (GSH), and brain-derived neurotrophic factor (BDNF) in the hippocampus and medial prefrontal cortex were examined. Results: The BLLL formula treatment at a dose of 8 × 1010 CFU/kg, but not at a dose of 2 or 4 × 1010 CFU/kg, improved CUS-induced depression-like behaviors in mice, as shown by the decrease in immobility time in the TST and FST and the increase in sucrose intake in the SPT. Further analysis revealed that BLLL treatment suppressed the CUS-induced increase in IL-1β, IL-6, and TNF-α mRNA and protein levels, as well as the CUS-induced decrease in IL-4, IL-10, and Ym-1 mRNA and/or protein levels in the hippocampus and medial prefrontal cortex. In addition, treatment with the BLLL formula countered the CUS-induced increase in nitrite and MDA levels and the CUS-induced decrease in GSH content and BDNF concentration in the hippocampus and medial prefrontal cortex. Conclusion: These results demonstrate that the novel probiotic formula BLLL ameliorates chronic stress-induced depression-like behavior in mice by suppressing neuroinflammation and oxido-nitrosative stress in the brain.

Study on the mechanisms of acupuncture combined with paroxetine in the treatment of mild to moderate depression based on DNA methylation analysis.

To explore the therapeutic effect of acupuncture combined with paroxetine for mild to moderate depression and the regulatory role of brain derived neurotrophic factor (BDNF) in patients based on DNA methylation. A total of 66 patients with mild to moderate depression who met the inclusion and exclusion criteria were randomly divided into an observation (acupuncture+medication) group and a control (medication) group, with 33 patients in each group, and other 25 healthy volunteers were taken as the healthy group. The patients of the control group were treated by oral administration of paroxetine 20 mg/d for 4 weeks. The patients of the observation group were treated by acupuncture stimulation of Zhongwan (CV12), Qihai (CV6), Zusanli (ST36), Sanyinjiao (SP6), Shangxing (GV23), Shuigou (GV26), Shaoshang (LU11), Yinbai (SP1) and Daling (PC7) (for 20 min, 3 times a week for 4 weeks) on the basis of medication treatment (the same as that of the control group). Before treatment, 2 and 4 weeks of treatment, and 2 weeks of follow-up, the therapeutic effect was assessed using Hamilton Depression Scale 17 (HAMD-17). The SPSS25.0 software was used to form a randomized grouping and to randomly select 25 patients from the observation group and 25 patients from the control group for blood collecting and data analysis. The blood samples were taken for assaying serum BDNF content and the methylation degree of BDNF gene promotor I with ELISA and MassARRAY techniques, respectively. 1) In comparison with those before treatment, the total score of HAMD-17, sleep disorder factor score, and anxiety somatization factor score of both the observation and control groups were significantly decreased after 2 and 4 weeks of treatment, and 2 weeks of follow-up (P<0.05), except sleep disorder factor score in the control group after 2 weeks of the treatment. Compared with the same time-points of the control group, the HAMD-17 total score and sleep disorder factor score of the observation group were decreased after 2 and 4 weeks of treatment, and 2 weeks of follow-up (P<0.05), while the anxiety somatization factor score was evidently decreased after 2 weeks of treatment (P<0.05). 2) Following 2 weeks of treatment, the total effective rate and markedly effective rate of the observation group were 80%(24/30)and 36.67% (11/30), respectively, being significantly higher than those ［(26.67% and 0 %)］ of the control group. After 4 weeks of treatment, the markedly effective rate of the observation group was 70.00% (21/30), being significantly higher than that 40% (12/30) of the control group (P<0.05), while the total effective rates of the observation and control groups were the same (100%). 3) Before the treatment, comparison among the healthy, observation and control groups showed no statistical significance in the methylation degree of each site (CpG1.2, CpG5.6, CpG8.9, CpG26, CpG27, CpG31, and CpG33.34) of BDNF gene promotor I, while after 4 weeks of the treatment, the methylation degree of CpG31 was considerably lower in the observation group than in the control group (P<0.05). 4) Before the treatment, the contents of serum BDNF of both observation and control group had no significant difference, but were evidently lower than that of the healthy group (P<0.05). Compared with that before treatment, the serum BDNF contents in both observation and control groups were significantly increased after the treatment (P<0.05), and was significantly higher in the observation group than in the control group (P<0.05). 5) The correlation analysis showed a negative correlation between the BDNF protein content and HAMD-17 score (correlation coefficient ρ=-0.686, P<0.01). Acupuncture may have an antidepressant role by decreasing CpG31 methylation of BDNF and increasing the serum content of BDNF protein in patients with depression. In addition, acupuncture combined with paroxetine has more advantages in treating mild to moderate depression than oral paroxetine alone, and can improve sleep disorders and anxiety somatization symptoms more quickly.

Benefits of exercise on cognitive impairment in alcohol use disorder following alcohol withdrawal.

Although most cognitive impairments induced by prolonged alcohol consumption tend to improve within the initial months of abstinence, there is evidence suggesting certain cognitive deficits may persist. This study aimed to investigate the impact of aerobic exercise on learning and memory in alcohol use disorder (AUD) mice following a period of abstinence from alcohol. We also sought to assess the levels of monoamine neurotransmitters in the hippocampus. To this end, we established an AUD mouse model through a two-bottle choice (sucrose fading mode and normal mode) and chronic intermittent alcohol vapor (combined with intraperitoneal injection) and randomly allocated mice into exercise groups to undergo treadmill training. Learning and memory abilities were assessed through the Morris water maze test and spontaneous activity was evaluated using the open field test. The levels of dopamine, norepinephrine, serotonin, and brain-derived neurotrophic factor in the hippocampus were quantified using enzyme-linked immunoassay (ELISA) kits. The findings reveal that after cessation of alcohol consumption, learning and memory abilities in AUD mice did not completely return to normal levels. The observed enhancement of cognitive functions in AUD mice through aerobic exercise may be attributed to restoring levels of monoamine neurotransmitters in the hippocampus, boosting brain-derived neurotrophic factor (BDNF) concentrations, and facilitating an increase in hippocampal mass. These results offer empirical evidence to support aerobic exercise as a viable therapeutic strategy to alleviate cognitive deficits associated with AUD.

Association between reduced plasma BDNF concentration and MMSE scores in both chronic schizophrenia and mild cognitive impairment

Reduced brain derived neurotrophic factor (BDNF) concentration is reported to be associated with a cognitive decline in schizophrenia, depending on the stage of the disease. Aim of the study was to examine the possible association between plasma BDNF and cognitive decline in chronic stable schizophrenia and mild cognitive impairment (MCI). The study included 123 inpatients of both sexes with schizophrenia, 123 patients with MCI and 208 healthy control subjects. Cognitive abilities were assessed using mini mental state examination (MMSE), Clock Drawing test (CDT) and cognitive subscale of the Positive and Negative Syndrome Scale (PANSS). Plasma BDNF concentration was determined using ELISA. BDNF concentration was lower in patients with schizophrenia and MCI compared to age-matched healthy controls and was similar in carriers of different BDNF Val/66Met genotypes. The MMSE and CDT scores were lower in patients with schizophrenia compared to healthy controls and subjects with MCI. Reduced plasma BDNF was significantly associated with lower MMSE scores in all subjects. BDNF concentration in patients with schizophrenia was not affected by clinical and demographic factors. BDNF Val66Met polymorphism was not associated with the MMSE scores in all participants. Further studies should include longitudinal follow-up and other cognitive scales to confirm these results and offer cognition-improving strategies to prevent cognitive decline in chronic schizophrenia.