Brain-derived Neurotrophic Factor Values Research Articles

Brain-derived neurotrophic factor as a promising neuromarker which could predict psychomotor developmental impairment in children with unrepaired congenital heart defects.

The aim of the study was to assess the predicting value of neuromarkers for psychomotor performances of congenital heart defect (CHD) patients before surgery, as until now the researchers only evaluated neuromarkers after the surgical treatment of the CHD. This cross-sectional study included children with CHD who did not receive treatment (interventional or cardiac surgery). Psychomotor development was evaluated using the Denver II Screening Test. Blood samples were collected for neuromarkers analysis: neuron-specific enolase (NSE), protein S100 (pS100), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP). We enrolled 77 children. Patients with CHD experienced more frequent developmental delays compared to healthy children (12-34% in the non-cyanotic group and 26-74% in the cyanotic group). The association between type of CHD and psychomotor impairment was statistically significant (p< 0.0001, RR =2.604, CI =2.07-3.26). Neuromarkers value was compared between cyanotic and non-cyanotic groups: NSE and BDNF values were higher in the cyanotic group, respectively, pS100 and GFAP had slightly higher values in the non-cyanotic group. A correlation coefficient of 0.35 (p= 0.023) was obtained between psychomotor development and BDNF level. An AUC of 0.72 was obtained for psychomotor development and BDNF in ROC analysis with the cut-off value of 5895 pg/ml. BDNF is showing moderate discriminative ability in predicting psychomotor development outcomes in pediatric patients with CHD.

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.

How does maternal anemia affect the levels of umbilical cord brain-derived neurotrophic factor?

ObjectiveIn this study, we aimed to evaluate the effect of maternal iron deficiency anemia on the umbilical cord level of brain-derived neurotrophic factor (BDNF), which plays a very important role in the central nervous system. MethodsOur research was planned as a quantitative, prospective, and analytical type of study. A total of 90 volunteers, term, singleton pregnant hospitalized in the Health Sciences University Ümraniye Training and Research Hospital Gynecology and Obstetrics Clinic between September 2021 and August 2022 were included in this study. While 45 of these pregnants were pregnant women with iron deficiency anemia (hemoglobin ≤ 110 g/L and serum ferritin level ≤ 12 μg/L), 45 cases were in the control group without iron deficiency anemia (hemoglobin > 110 g/L, serum ferritin > 12 μg/L). When pregnant were admitted to the hospital, blood samples were taken to analyze hemoglobin, mean cell volume (MCV), iron, unsaturated iron binding capacity, total iron binding capacity, serum ferritin, transferrin, and CRP levels. Also, we noted the maternal age, gravida, parity, birth weight, head circumference, type of birth, 1. minute Apgar score, and 5. minute Apgar score. During the delivery; after the umbilical cord had been clamped and cut, we took 5 cc of umbilical cord blood. Then, we put it in the serum-separating laboratory tubes. After we centrifuged these blood samples, we put the serum parts in the Eppendorf tubes to be stored at −80 degrees Celsius. At the end of the study, we calculated the level of BDNF using special human brain-derived neurotrophic factor ELISA kits. The umbilical cord BDNF levels of the maternal iron deficiency anemia group and the control group were compared statistically. ResultsWhen we evaluated the fetal umbilical cord BDNF values of 90 participants, the median value BDNF in the babies of 45 anemic mothers was 3.16 (IQR 0.73), and the median BDNF value of the babies of 45 healthy mothers was 5.37 (IQR 1.02). We found a statistical difference between BDNF and hemoglobin, hematocrit, MCV, and iron values between these two groups. ConclusionIn conclusion, the BDNF value of the babies of healthy individuals is higher than that of anemic individuals. Our study showed that the amount of BDNF in the umbilical cord blood was significantly affected by maternal iron deficiency anemia.

Nutrient patterns in relation to metabolic health status and serum levels of brain-derived neurotrophic factor (BDNF) and adropin in adults

The present study aimed to investigate the association of nutrient patterns (NPs) with metabolic health status and serum levels of brain-derived neurotrophic factor (BDNF) and adropin in Iranian adults. This cross-sectional survey was performed on 527 adults aged 20–60 years in Isfahan, Iran. To evaluate dietary intake, a validated 168-item semi-quantitative food frequency questionnaire (FFQ) was used. Participants were categorized as metabolically healthy (MH) and metabolically unhealthy (MU) according to their glycemic and lipid profile, insulin resistance (IR), and inflammation status. An overnight fasting blood sample was collected from each participant and serum levels of BDNF and adropin were assessed. A total of 42.50% of participants were recognized as MU. Three NPs were recognized by factor analysis that labeled as “high animal protein” (NP1), “high vegetable” (NP2), and “high carbohydrate” (NP3) patterns. Moderate adherence to NP2 was related to a lower risk of MU (ORT2 vs. T1 = 0.38, 95% CI: 0.18–0.76). Moreover, high adherence of NP2 (T3 vs. T1) was inversely associated with hypertriglyceridemia (OR = 0.27, 95% CI: 0.11–0.65; P-trend < 0.001) and high hs-CRP values (OR = 0.29, 95% CI: 0.09–1.00; P-trend = 0.03). No significant association was observed between adherence of NP1 and NP3 with MU in crude and adjusted models. However, negative associations were found between moderate adherence to NP3 and insulin resistance (IR) (OR = 0.23, 95% CI: 0.06–0.91) as well as high adherence to NP1 and hypertension (OR = 0.23, 95% CI: 0.09–0.61; P-trend < 0.001). NPs were not associated with serum BDNF and adropin values.

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.

Brain-derived neurotrophic factor (BDNF) as a potential marker of endometriosis: a systematic review and meta-analysis

BackgroundThe existing literature on the association between BDNF protein levels and endometriosis presents inconsistent findings. This systematic review and meta-analysis aim to synthesize the available evidence and evaluate the possible relationship between BDNF protein levels and endometriosis.MethodsElectronic databases (PubMed, Embase, Scopus, PsycINFO, and Web of Science) were used to conduct a comprehensive literature search from inception to June 2023. The search strategy included relevant keywords and medical subject headings (MeSH) terms related to BDNF, endometriosis, and protein levels. A random-effects model was used for the meta-analysis, and to explore heterogeneity subgroup analyses were performed. funnel plots and statistical tests were used for assessing the publication bias.ResultsA total of 12 studies were included. The pooled standardized mean difference (SMD) of BDNF levels between women with endometriosis and controls was 0.87 (95% confidence interval [CI] 0.34 to 1.39, p = 0.001; I2 = 93%). The results showed that blood levels of BDNF are significantly higher in endometriosis patients (SMD: 1.13 95% CI 0.54 to 1.73, p = 0.0002; I2 = 93%). No significant publication bias was observed based on the results of Egger’s regression test ((p = 0.15).ConclusionThis study revealed a significant difference between patients diagnosed with endometriosis and healthy control in the level of BDNF. The results indicate that women with endometriosis have higher levels of BDNF. Further studies are needed to be undertaken to investigate the role of BDNF in endometriosis pathophysiology and the diagnostic value of BDNF in endometriosis.

BDNF/TrkB signaling in stable coronary artery disease

Aim. To study the serum content of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) in patients with coronary artery disease (CAD) and evaluate the relationship of BDNF/TrkB signaling with the severity of coronary atherosclerosis, systemic inflammation (IL-2, IL-4, IL-6, IL-10, TNF-α) and angiogenesis (VEGF).Material and methods. The study included 99 patients with stable CAD who underwent coronary angiography and 30 healthy volunteers. Coronary atherosclerosis was assessed using the Gensini score (GS). In blood serum, the concentrations of BDNF, TrkB, VEGF, IL-2, IL-4, IL-6, IL-10, TNF-α were determined using the enzyme immunoassay. Cluster, correlation, and regression analyzes were used.Results. In patients with CAD, a wide range of variations in BDNF concentrations was observed. To determine homogeneous groups using the k-means clustering, three clusters with different BDNF/TrkB axis vectors were identified. Patients differed in the severity of coronary atherosclerosis, the manifestation of the inflammatory reaction, and the intensity of angiogenesis. In patients with initial and moderate atherosclerotic changes in the coronary arteries, a normal concentration of BDNF and an increased level of TrkB (22,35/1,18 ng/ml) were noted. In patients with severe coronary atherosclerosis, two different BDNF/TrkB variants have been identified. Decreased BDNF and increased TrkB (6,0/1,52 ng/ml) were associated with low VEGF and increased IL-6. Elevated BDNF and normal TrkB values (26,95/0,96 ng/ml) were characteristic of patients with high VEGF expression, indicating angiogenesis activation and/or vulnerable plaques. A direct relationship between BDNF and VEGF (r=0,536, p&lt;0,001) and an inverse relationship with TrkB (r=-0,301, p=0,019), IL-6 (r=-0,306, p=0,002) was revealed. TrkB levels were correlated with TNF-α (r=0,403, p=0,001). Regression analysis showed that BDNF expression is influenced by TrkB (β=-0,237, p=0,009), VEGF (β=0,490, p&lt;0,001), IL-6 (β=-0,339, p&lt;0,001).Conclusion. In patients with stable CAD, different levels of BDNF/TrkB expression were found, which were associated with coronary atherosclerosis severity. BDNF/TrkB signaling is involved in the regulation of inflammation and angiogenesis in stable CAD.

Cognitive impairment is associated with BDNF-TrkB signaling mediating synaptic damage and reduction of amino acid neurotransmitters in heart failure.

Heart failure (HF) is often accompanied by cognitive impairment (CI). Brain-derived neurotrophic factor (BDNF) deficiency is closely associated with CI. However, the role and mechanism of BDNF in HF with CI is still not fully understood. Here, the case-control study was designed including 25 HF without CI patients (HF-NCI) and 50 HF with CI patients (HF-CI) to investigate the predictive value of BDNF in HF-CI while animal and cell experiments were used for mechanism research. Results found that BDNF levels in serum neuronal-derived exosomes were downregulated in HF-CI patients. There was no significant difference in serum BDNF levels among the two groups. HF rats showed obvious impairment in learning and memory; also, they had reduced thickness and length of postsynaptic density (PSD) and increased synaptic cleft width. Expression of BDNF, TrkB, PSD95, and VGLUT1 was significantly decreased in HF rats brain. In addition, compared with sham rats, amino acids were significantly reduced with no changes in the acetylcholine and monoamine neurotransmitters. Further examination showed that the number of synaptic bifurcations and the expression of BDNF, TrkB, PSD95, and VGLUT1 were all decreased in the neurons that interfered with BDNF-siRNA compared with those in the negative control neurons. Together, our results demonstrated that neuronal-derived exosomal BDNF act as effective biomarkers for prediction of HF-CI. The decrease of BDNF in the brain triggers synaptic structural damage and a decline in amino acid neurotransmitters via the BDNF-TrkB-PSD95/VGLUT1 pathway. This discovery unveils a novel pathological mechanism underlying cognitive impairment following heart failure.

Comparing distributed versus massed practice on functional recovery and Brain-Derived Neurotrophic Factor (BDNF) in acute stroke subjects.

Globally, stroke is known to be one of the major health problems, resulting in disability among an aging population. Rehabilitation is a process of re-learning of skills, lost due to brain injury. Many factors influence motor learning post neurological insult and practice is one of the key factors which influence relearning or reacquisition of lost motor skills. Practice can be varied concerning order (blocked or random), scheduling (massed or distributed), or whole and part practice. The study observed the effect of variations in practice schedules on motor and functional recovery. Thirty-two acute stroke subjects were recruited and equally divided into two groups (16 in massed and 16 in distributed). Both groups received an accelerated skill acquisition program (ASAP) for six sessions a week for 2 weeks. Pre- and post-outcome measures included stroke rehabilitation assessment of movement (STREAM) for motor recovery, modified Barthel index (MBI) for functional recovery, and brain-derived neurotrophic factor (BDNF) for neuroplasticity. The median scores of participants in the massed practice group before the intervention, of STREAM total, MBI, and BDNF were 23.5, 19, and 0.65, respectively, whereas post values of STREAM total, MBI, and BDNF were 40.5, 60.5, and 0.75, respectively. The median scores of the distributed practice group of the pre-STREAM total, MBI, and BDNF were 23.5, 6.5, and 0.70, respectively, whereas the post-STREAM total, MBI, and BDNF were 41, 45.5, and 0.80, respectively. P-value was reported to be <0.05 while comparing pre- and post-values of STREAM, MBI, and BDNF within both intervention groups. The median change scores of STREAM, MBI, and BDNF reported P ≥ 0.05 when compared between the groups. Both the groups had significant recovery post-intervention designed based on ASAP, about impairment mitigation, pursuing skilled movement leading to significant functional gains. Appropriate timing along with optimal dosage became an active ingredient in functional recovery in acute stroke subjects. The distributed practice might have added effect of spacing, resulting in easier learning and accuracy of skills. The study reveals that distributed practice can be part of regular clinical practice to enhance functional recovery in acute stroke rehabilitation.

Association between dietary insulin index and load with brain derived neurotrophic factor, adropin and metabolic health status in Iranian adults

The associations of high potential insulinogenic foods with metabolic health (MH) status and brain-derived neurotrophic factor (BDNF) and adropin were not investigated quite enough. We examined the relationship between dietary insulin load (DIL) and dietary insulin index (DII) with MH and serum levels of BDNF and adropin among Iranian adults. This cross-sectional investigation accomplished among 527 Iranian middle-aged adults (54.3% men). Dietary information was obtained by a validated food frequency questionnaire. Anthropometric indices and blood pressure were assessed. For measuring lipid and glycemic profile and serum levels of BDNF and adropin, blood samples were assembled after 12 h of fasting. MH was defined based on lipid and glycemic profile, high blood pressure, insulin resistance and chronic inflammation. After adjustments all confounders, participants in the highest tertile of DII compared to the lowest one had a 115% increased odds for metabolic unhealthy (MU) profile (ORT3 vs. T1 = 2.15, 95% CI 1.03–4.49). However, DIL was not related to MU. Higher DII was additionally associated with high blood pressure, in maximally-adjusted model (ORT3 vs. T1 = 3.57, 95% CI 1.61–7.92). Moreover, moderate DIL was significantly associated with hypertriglyceridemia (ORT2 vs. T1 = 2.56, 95% CI 1.01–6.45). Each tertile increase in DII or DIL was not significantly associated with serum BDNF or adropin values. Greater DII was associated with higher chance of MU and hypertension in Iranian adults; but no association was found between DIL and metabolic health. DIL or DII was not related to circulating BDNF or adropin. To confirm these findings, additional prospective investigations are required.

Association between Mediterranean dietary pattern with sleep duration, sleep quality and brain derived neurotrophic factor (BDNF) in Iranian adults

Data on the association between Mediterranean diet, sleep and brain-derived neurotrophic factor (BDNF) were limited in Middle Eastern populations. We examined the association between Mediterranean dietary pattern with sleep quality/quantity, and serum BDNF in Iranian adults. This cross-sectional study was performed among 535 middle-aged adults (54% men), selected by multistage cluster random sampling method. The Pittsburgh sleep quality index and a validated food frequency questionnaire were used to assess sleep quality, sleep quantity, and Mediterranean diet score (MDS). Twelve-hour fasting blood samples were taken to evaluate serum BDNF values. Participants in the highest tertile of MDS, in comparison to those in the lowest tertile, had lower odds of having short sleep (OR = 0.44, 95%CI: 0.21–0.91) and poor sleep quality (OR = 0.48, 95%CI: 0.22–0.96), after adjustment for potential confounders. Among specific domains of sleep quality, lower odds of subjective sleep quality, sleep latency, and daytime dysfunction were associated with increased MDS. Higher adherence to MDS among individuals with overweight or obesity reduced the odds of having short sleep; this relation was not seen among individuals with normal weight. In contrast, the association between sleep quality and the MDS was significant in individuals with normal weight, but not those with overweight or obesity. Participants with higher adherence to MDS had lower odds for low BDNF values; however, this relation was not statistically significant. Overall, Iranian adults with a higher adherence to MDS had considerably lower odds of having short sleep and poor sleep quality. BDNF would not be an intermediate molecule for this connection.

BDNF and KISS-1 Levels in Maternal Serum, Umbilical Cord, and Placenta: The Potential Role of Maternal Levels as Effect Biomarker

Brain-derived neurotrophic factor (BDNF) and kisspeptin-1 (KISS-1) regulate placental development and fetal growth. The predictive value of maternal serum BDNF and KISS-1 concentrations for placental and umbilical cord levels has not yet been explored. The influence of prenatal lead (Pb) and cadmium (Cd) exposure and maternal iron status on BDNF and KISS-1 levels is also unclarified and of concern. In a pilot cross-sectional study with 65 mother–newborn pairs, we analyzed maternal and cord serum levels of pro-BDNF, mature BDNF, and KISS-1, BDNF, and KISS-1 gene expression in placenta, Pb and Cd in maternal and umbilical cord blood (erythrocytes), and placenta. We conducted a series of in vitro experiments using human primary trophoblast cells (hTCs) and BeWo cells to verify main findings of the epidemiological analysis. Strong and consistent correlations were observed between maternal serum levels of pro-BDNF, mature BDNF, and KISS-1 and corresponding levels in umbilical serum and placental tissue. Maternal red blood cell Pb levels were inversely correlated with serum and placental KISS-1 levels. Lower expression and release of KISS-1 was also observed in Pb-exposed BeWo cells. In vitro Pb exposure also reduced cellular BDNF levels. Cd-treated BeWo cells showed increased pro-BDNF levels. Low maternal iron status was positively associated with low BDNF levels. Iron-deficient hTCs and BeWo cells showed a consistent decrease in the release of mature BDNF. The correlations between maternal BDNF and KISS-1 levels, placental gene expression, and umbilical cord serum levels, respectively, indicate the strong potential of maternal serum as predictive matrix for BDNF and KISS-1 levels in placentas and fetal sera. Pb exposure and iron status modulate BDNF and KISS-1 levels, but a clear direction of modulations was not evident. The associations need to be confirmed in a larger sample and validated in terms of placental and neurodevelopmental function.

Serum brain-derived neurotrophic factor levels in patients with schizophrenia and methamphetamine addiction: correlation with Mini-Mental State Examination (MMSE).

Methamphetamine use can induce psychosis resembling acute schizophrenia spectrum psychosis, making it challenging to differentiate between the two based on symptoms alone. Brain-derived neurotrophic factor (BDNF) exerts a critical role in hippocampal neural plasticity, influencing critical cognitive functions such as memory and learning. This study aimed to determine the role of serum BDNF levels in schizophrenia and methamphetamine addiction. A case-control study was conducted involving 50 patients with schizophrenia, 50 patients with methamphetamine addiction, and 50 healthy control subjects recruited from Ibn-Rushed Psychiatric Teaching Hospital in Baghdad. Cognitive impairment was assessed using the Mini-Mental State Examination (MMSE), while serum BDNF levels were measured using ELISA following standardized protocols. The findings revealed significantly lower median levels of BDNF (0.36 pg/ml) in patients with schizophrenia compared to both the control group (0.51 pg/ml) and the methamphetamine group (0.72 pg/ml). Moreover, there was a significant difference observed between the methamphetamine group and the control group. At a cut-off value of BDNF=0.37 pg/ml, the sensitivity and specificity of BDNF in differentiating between schizophrenia and methamphetamine addiction were 84% and 70%, respectively. Serum level of BDNF could be used to differentiate between schizophrenia and methamphetamine addiction when clinical distinctions are challenging to detect.

Total fat and omega-3 fatty acids intake in relation to serum brain-derived neurotrophic factor (BDNF) levels and psychological disorders in Iranian adults

Considering contradictory findings of previous investigations and growing prevalence of psychological disorders, we investigated association between dietary total fat and omega-3 fatty acids intake with serum brain-derived neurotrophic factor (BDNF) levels, depression, anxiety and psychological distress in Iranian adults. Using a multistage cluster random sampling method, 533 middle-aged adults were included in this cross-sectional study. A validated semi-quantitative 168-item food frequency questionnaire was used to examine dietary intakes. A 12-h fasting blood sample was drawn to measure serum BDNF. Serum BDNF values in the first decile were considered low level. Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ) were used to assess depression, anxiety and psychological distress. A U-shaped relationship between fat intake and prevalence of anxiety and distress was found. The third quartile of fat intake compared to the first quartile was significantly related to 80% decreased odds of depression (OR = 0.20, 95% CI 0.05–0.80), in fully-adjusted model. Participants in the third quartile of fat intake compared to those in the first quartile had significantly 45% lower odds for distress, in the crude model (OR = 0.55, 95% CI 0.33–0.92); however, this association disappeared after considering confounders. There was no significant association between omega-3 fatty acids intake and odds of depression, anxiety or distress. Prevalence of low-BDNF values was higher in participants with depression, as compared to non-depressed subjects (14.9 vs. 9%; P = 0.06). This cross-sectional study illustrated a U-shaped relationship between fat intake and prevalence of anxiety and distress. Moderate intake of fat was related to lower odds of depression. Prevalence of low-BDNF values was slightly higher in subjects with depression compared to non-depressed individuals.

Expression Pattern and Value of Brain-Derived Neurotrophic Factor in Periodontitis

BackgroundPeriodontitis is a common human disease with an increasing incidence. Brain-derived neurotrophic factor (BDNF) is known to play a crucial role in the regeneration of periodontal tissue; however, the expression, methylation level, molecular function, and clinical value of BDNF in periodontitis require further investigation. This study aimed to investigate the expression and potential functions of BDNF in periodontitis. MethodsRNA expression and methylation data were obtained from the Gene Expression Omnibus (GEO) database, and the expression and methylation levels of BDNF were compared between periodontitis and normal tissues. In addition, bioinformatics analysis was performed to investigate the downstream molecular functions of BDNF. Finally, Reverse transcription Quantitative real-time polymerase chain reaction was performed to determine the level of BDNF expression in periodontitis and normal tissues. ResultsGEO database analysis revealed that BDNF was hypermethylated in periodontitis tissues and that its expression was downregulated. Reverse transcription Quantitative real-time polymerase chain reaction confirmed that BDNF expression was downregulated in periodontitis tissues. Several genes that interact with BDNF were determined using a protein–protein interaction network. Functional analysis of BDNF revealed that it was enriched in the Gene Ontology terms cytoplasmic dynein complex, glutathione transferase activity, and glycoside metabolic process. Kyoto Encyclopedia of Genes and Genomes analysis suggested that BDNF was associated with the mechanistic target of rapamycin signaling pathway, fatty acid metabolism, the Janus kinase-signal transducer and activator of transcription signaling pathway, glutathione metabolism, and others. Furthermore, the level of BDNF expression was correlated with the immune infiltration degree of B cells and CD4+ T cells. ConclusionsThis study shown that BDNF was hypermethylated and downregulated in periodontitis tissues, which could be a biomarker and treatment target of periodontitis.

Evaluation of maternal serum and umbilical cord brain-derived neurotrophic factor (BDNF) levels in COVID-19-infected pregnancies.

COVID-19 is a disease that affects and damages the neurological system. The aim of this study was to evaluate the fetal neurodevelopmental status through maternal serum and umbilical cord BDNF levels. In this prospective study, 88 pregnant women were evaluated. Demographic and peripartum characteristics of the patients were recorded. Samples were collected from pregnant women for maternal serum and the umbilical cord BDNF levels during delivery. In this study, 40 pregnant women hospitalized with COVID-19 formed the infected group and 48 pregnant women without COVID-19 formed the healthy control group. Demographic and postpartum characteristics were similar in both groups. Maternal serum BDNF values were significantly lower in the COVID-19 infected group (1597.0 ± 337.3 pg/ml) than in the healthy group (1783.2 ± 394.1 pg/ml) (p=0.019). Fetal BDNF levels were 1794.9 ± 440.3 pg/ml in the healthy group and 1691.0 ± 368.6 pg/ml in COVID-19 infected pregnant women group and statistically similar between groups (p=0.232). Results showed that while maternal serum BDNF levels decreased in the presence of COVID-19, there was no difference in umbilical cord BDNF levels. This may be an indication that the fetus is not affected and is protected.

BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges.

The primary objective of this paper is to (1) provide a summary of human studies that have used brain derived neurotrophic factor (BDNF) as a biomarker, (2) review animal studies that help to elucidate the mechanistic involvement of BDNF in the development and maintenance of neuropathic pain (NP), and (3) provide a critique of the existing measurement techniques to highlight the limitations of the methods utilized to quantify BDNF in different biofluids in the blood (i.e., serum and plasma) with the intention of presenting a case for the most reliable and valid technique. Lastly, this review also explores potential moderators that can influence the measurement of BDNF and provides recommendations to standardize its quantification to reduce the inconsistencies across studies. In this manuscript we examined the literature on BDNF, focusing on its role as a biomarker, its mechanism of action in NP, and critically analyzed its measurement in serum and plasma to identify factors that contribute to the discrepancy in results between plasma and serum BDNF values. A large heterogenous literature was reviewed that detailed BDNF's utility as a potential biomarker in healthy volunteers, patients with chronic pain, and patients with neuropsychiatric disorders but demonstrated inconsistent findings. The literature provides insight into the mechanism of action of BDNF at different levels of the central nervous system using animal studies. We identified multiple factors that influence the measurement of BDNF in serum and plasma and based on current evidence, we recommend assessing serum BDNF levels to quantify peripheral BDNF as they are more stable and sensitive to changes than plasma BDNF. Although mechanistic studies clearly explain the role of BDNF, results from human studies are inconsistent. More studies are needed to evaluate the methodological challenges in using serum BDNF as a biomarker in NP.

Brain-derived neurotrophic factor (BDNF) and the capute scales in offspring of mothers with normal and deficient vitamin D levels

Background: Vitamin D deficiency during pregnancy is associated with a child's neurocognitive development. During the COVID-19 pandemic, the Capute Scales have become ineffective because requiring face-to-face interaction to examine children's neurocognitive development. Brain-Derived Neurotrophic Factor (BDNF) is an alternative method to determine children's neurocognitive development through blood sampling. This study aims to evaluate the relationships between BDNF and the Capute Scales in the offspring of mothers with vitamin D levels. Methods: A diagnostic study from 14 community health centers in Semarang City, Central Java, Indonesia, was conducted. The study was performed from August 2017 until August 2018 and included vitamin D level records at 20–24 weeks of normal gestation in 2017 from all single births at these community health centers. The cases were divided into two groups: 30 children born to mothers with normal vitamin D levels (25(OH)D &gt; 20 ng/mL) and 30 children born to mothers with vitamin D deficiency (25(OH)D &lt; 20 ng/ml). This study aimed to assess the relationship between BDNF levels and the Capute Scales of children aged 2 years and to determine the cut-off value based on each group's examination of BDNF levels. Results: The mean age of pregnant women whose vitamin D levels were checked was 29.32 years. The cut-off value of BDNF among the two groups was 7968 pg/mL. Of the 55 samples that met the Capute Scales criteria, 44 had a BDNF value less than the cut-off value, and 11 samples had a BDNF value more than the cut-off value. Meanwhile, of the five samples that met the Capute Scales criteria and were suspected of mental retardation, three had a BDNF value less than the cut-off value, and two had a BDNF value more than the cut-off value. The sensitivity, specificity, positive, and negative predictive values were 80%, 60%, 0.93, and 0.15, respectively. Conclusions: BDNF levels can be an alternative neurocognitive examination in children born to mothers with normal and deficient vitamin D levels. BDNF is a growth factor that plays an important role in neurons' differentiation, growth, and survival in the postnatal phase.

Role of Neurogenesis and Oxidative Stress in Epilepsy (Study on Plasma Brain Derived Neurotrophic Factor and Malondialdehyde Level)

BACKGROUND: Epilepsy is a neurological disorder. Its incidence in Indonesia was 700,000–1,400,000 cases and 40–50% occurred in children. About 30–40% of cases in children had uncontrolled seizures. Biomarkers are needed to assess the prognostic value of patients with uncontrolled epilepsy. Malondialdehyde (MDA) and brain-derived neurotrophic factor (BDNF) are one of the prognostic biomarkers related to uncontrolled epilepsy to see the effect of oxidative stress and neuroplasticity. AIM: The objective of the study was to examine cut off value of plasma BDNF and MDA level; and to compare plasma BDNF and MDA levels in uncontrolled and controlled epilepsy patients. METHODS: The research usedanalytic observational with cross-sectional approach. Number of respondents was 30 patients of epilepsy who came to Ulin Hospital Banjarmasin. Respondents were divided into two groups (controlled and uncontrolled epilepsy). Blood plasma was examined for MDA with a spectrophotometer and BDNF with ELISA. Data were analyzed by t-test with 95% confidence level. RESULTS: 11 children were found in the uncontrolled epilepsy group and 19 children with controlled epilepsy. The result showed that there were significant differences between type of therapy and developmental disorders/other diseases with epilepsy status. There was no significant differences of plasma BDNF in epilepsy status (controlled and uncontrolled epilepsy), and there was also no significant differences of plasma MDA in epilepsy status (controlled and uncontrolled epilepsy). CONCLUSION: There were no significant differences of plasma BDNF and MDA in epilepsy status.

Electrical muscle stimulation in young adults: effect of muscle volume on brain-derived neurotrophic factor levels.

Electrical muscle stimulation (EMS) is known to be effective at stimulating brain-derived neurotrophic factor (BDNF) levels, but the relationship between the volume of muscle stimulated and BDNF levels is not clear. The purpose of this study was to quantify BDNF as a function of muscle volume stimulated in young adults. Twelve young adults (male, n = 9, age = 27.3 ± 5.5years) were enrolled in this study. Participants completed three testing conditions in randomized order: 23min of maximum tolerated bilateral stimulation of (1) the quadriceps muscle or (2) the musculature of the entire lower limbs and (3) control testing and retesting after 23min without an intervention. Blood samples were collected before, immediately after, 20min after, and 40min after the intervention when EMS was applied to the thighs or the entire lower limb conditions. Serum obtained from blood collection was used for BDNF analysis. The delta value of BDNF for the test and retest in the control condition was - 42.1 ± 73.8pg/mL, and there was no significant difference between the test and retest BDNF. Compared to stimulation of the quadriceps muscle, stimulation of the entire lower limbs produced significantly higher BDNF at 20min post-treatment than those at pre-treatment or 40min post-treatment, and BDNF was also significantly higher immediately post-treatment than those at pre-treatment. Only stimulation of the quadriceps muscle did not induce a significant change between pre- and post-treatment. Our findings suggest that the volume of muscle stimulation is important for increased BDNF.