Blood Brain-derived Neurotrophic Factor Levels Research Articles

Brain-Derived Neurotrophic Factor (BDNF) Is Associated with Platelet Activity and Bleeding Tendency in Patients with Gaucher Disease.

Bleeding tendency, a prominent feature of patients with Gaucher disease (GD), is associated with abnormal platelet function. Brain-derived neurotrophic factor (BDNF) is a protein with neuroprotective potential stored in alpha granules of circulating platelets. Here we studied BDNF levels in 50 patients with type I GD (GD1) and their correlation with platelet activity and bleeding tendency. Flow cytometry was used to test unstimulated and stimulated measurement of platelet surface-activated expression of αIIbβ3 integrin, P-selectin and lysosomal-associated membrane protein (LAMP3/CD63). Serum and plasma BDNF levels were quantified using ELISA. The bleeding history was recorded by a bleeding questionnaire. Serum BDNF levels were positively correlated with platelet count and moderately correlated with unstimulated and stimulated platelet P-selectin expression. Patients with more than one bleeding manifestation were shown to have lower serum BDNF levels, albeit similar platelet count. Plasma BDNF levels were significantly elevated in splenectomized patients and showed a moderate positive correlation with stimulated platelet CD63 expression. These observations demonstrate the first association between BDNF levels in the peripheral blood with platelet dysfunction and increased bleeding manifestation. The role of measuring serum BDNF for assessing platelet alpha degranulation defects and bleeding risk in patients with GD and the general population needs further study.

Association of serum brain-derived neurotrophic factor with hepatic enzymes, AST/ALT ratio, and FIB-4 index in middle-aged and older women.

Substantial evidence suggests an important role of liver function in brain health. Liver function is clinically assessed by measuring the activity of hepatic enzymes in the peripheral blood. Brain-derived neurotrophic factor (BDNF) is an important regulator of brain function. Therefore, we hypothesized that blood BDNF levels are associated with liver function and fibrosis. To test this hypothesis, in this cross-sectional study, we investigated whether serum BDNF concentration is associated with liver enzyme activity, aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio, and fibrosis-4 (FIB-4) index in middle-aged and older women. We found that serum BDNF level showed a significant positive association with ALT and γ-glutamyltranspeptidase (GGT) activity and negative association with FIB-4 index, and a trend of negative association with the AST/ALT ratio after adjustment for age. Additionally, these associations remained statistically significant even after adjustment for body mass index (BMI) and fasting blood glucose level. These results demonstrate associations of serum BDNF levels with liver enzymes and hepatic fibrosis-related indices, which may underlie liver-brain interactions.

Reduced plasma BDNF concentration and cognitive decline in veterans with PTSD

Post-traumatic stress disorder (PTSD) is a trauma and stress related disorder frequently associated with cognitive decline. War veterans with PTSD have a higher risk of developing dementia than healthy subjects. Brain derived neurotrophic factor (BDNF) is an important protein that modulates plasticity, memory consolidation and cognitive processes. Lower circulating BDNF levels were related to memory impairment and cognitive deterioration. The aim of this study was to evaluate cognitive deterioration and plasma BDNF concentration in 120 veterans with combat related PTSD, 120 healthy controls, 47 subjects with mild cognitive impairment (MCI) and 76 patients with Alzheimer's disease (AD), and to assess if plasma BDNF concentration might be used as biomarker of cognitive deterioration. Veterans with PTSD had significantly decreased plasma BDNF concentration and worse cognitive performances (assessed using the Mini Mental State Examination, Clock Drawing test and Montreal Cognitive Assessment scores/categories) than healthy subjects, and similarly reduced plasma BDNF and cognitive decline as MCI subjects. Reduced plasma BDNF was found in cognitively impaired subjects. These results suggest that veterans with PTSD should be closely monitored in order to early detect and predict cognitive worsening and promote interventions that might help restore blood BDNF levels and cognitive functions.

Brain‐derived Neurotrophic Factor in Duchenne Muscular Dystrophy Myopathy

Brain‐derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) are crucial for neuronal growth and survival, and loss of this signaling nexus invariably leads to neurodegeneration. In a small cohort of Duchenne muscular dystrophy (DMD) patients we found that BDNF blood levels positively correlated with better heart function, and carriers of the common BDNF single nucleotide polymorphism rs6265 (Val66‐Met) exhibited significantly worse skeletal muscle function and earlier loss of ambulation, compared to non‐carriers. We thus hypothesized that BDNF/TrkB signaling delays progression of myopathy in DMD. To test this hypothesis, we administered the TrkB agonist 7,8‐dihydroxyflavone (DHF) to mdx mice in their drinking water for 26 weeks, beginning at 8 weeks of age. Based on functional assessment using the hang test, DHF treatment preserved skeletal muscle function compared to vehicle‐treated controls. Trichrome staining of gastrocnemius and cardiac tissues also showed reduced levels of fibrosis, which correlated with BDNF expression levels. Using humanized BDNF polymorphic mice, which have the Val66‐Met mutation, and mice with a point mutation in the equivalent position of murine BDNF (Val68‐Met), we found that skeletal muscle strength was significantly reduced in mice with the Met allele, compared to Val/Val littermate controls. Although Val/Met and Met/Met mice weighed considerably more than control mice, they exhibited significantly increased activity, as measured by voluntary wheel running. Based on transmission electron microscopy, individual gastrocnemius muscle fibers of Met/Met mice were smaller and less organized compared to those of Val/Val. Finally, we crossed Val66‐Met mice with mdx mice to assess the effects of the BDNF polymorphism on the dystrophic background. As was found for DMD patients who harbor the BDNF rs6265 polymorphism, dystrophic mice with the Met allele exhibited worse skeletal muscle function compared to noncarriers. Considered together, our results indicate that BDNF plays a protective role in dystrophic muscle and might represent a novel therapeutic candidate for DMD myopathy.

Correlation between antenatal magnesium sulfate (MgSO4) total dose and delivery time interval with umbilical cord blood brain-derived neurotrophic factor (BDNF) levels as a neuroprotection strategy in preterm birth

Background: Administration of antenatal magnesium sulfate (MgSO4) to pregnant women is thought to increase the synthesis of Brain-Derived Neurotrophic Factor (BDNF), which functions as a nerve-growth factor for the process of neurogenesis and also strengthen neuronal resilience in the hypoxic condition that occurs during preterm delivery. Protocols for administering antenatal MgSO4 differ between countries and institutions. One of the concerns is whether the dose is given and the time interval to delivery has a big contribution towards a better fetal outcome. These relationships have not been studied before. This study aimed to analyze the correlation of the total dose of MgSO4 and time interval to delivery with BDNF levels in cord blood. Methods: This study enrolled 72 pregnant women who will deliver the baby prematurely, with gestational age 28-34 weeks. Subjects were divided into three protocols groups: (1) 4 g iv. only, (2) 4 g iv. initial continued with 1 g/hours until maximum 24 hours, and (3) 6 g iv. initial continued with 2 g/hours until a maximum of 24 hours. At the time of delivery, cord blood of preterm babies was collected. The antenatal MgSO4 total dose and time interval to delivery were collected, and BDNF serum levels were then measured with enzyme-linked immunosorbent assay (ELISA). The correlation between antenatal MgSO4 total dose and time interval to delivery with BDNF levels was analyzed using Spearman’s correlation test. Result: There was a weak significant correlation of antenatal MgSO4 total dose and BDNF cord blood levels (p<0.001; r=0.381). There was no significant correlation between delivery time interval and BDNF cord blood levels (p=0.44; r=0.092). Conclusion: Regarding the weak correlation of total dose and time interval to delivery with BDNF, we suggest that all protocols provide comparable outcomes if seen only from the BDNF increase perspective.

Brain-Derived Neurotrophic Factor Levels in Cord Blood from Growth Restricted Fetuses with Doppler Alteration Compared to Adequate for Gestational Age Fetuses.

Background and Objectives: Fetal growth restriction (FGR) is a severe obstetric disease characterized by a low fetal size entailing a set of undesired consequences. For instance, previous studies have noticed a worrisome association between FGR with an abnormal neurodevelopment. However, the precise link between FGR and neurodevelopmental alterations are not yet fully understood yet. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophin strongly implicated in neurodevelopmental and other neurological processes. In addition, serum levels of BDNF appears to be an interesting indicator of pathological pregnancies, being correlated with the neonatal brain levels. Therefore, the aim of this study is to analyze the blood levels of BDNF in the cord blood from fetuses with FGR in comparison to those with weight appropriate for gestational age (AGA). Materials and Methods: In this study, 130 subjects were recruited: 91 in group A (AGA fetuses); 39 in group B (16 FGR fetuses with exclusively middle cerebral artery (MCA) pulsatility index (PI) < 5th percentile and 23 with umbilical artery (UA) PI > 95th percentile). Serum levels of BDNF were determined through ELISA reactions in these groups. Results: Our results show a significant decrease in cord blood levels of BDNF in FGR and more prominently in those with UA PI >95th percentile in comparison to AGA. FGR fetuses with exclusively decreased MCA PI below the 5th percentile also show reduced levels of BDNF than AGA, although this difference was not statistically significant. Conclusions: Overall, our study reports a potential pathophysiological link between reduced levels of BDNF and neurodevelopmental alterations in fetuses with FGR. However, further studies should be conducted in those FGR subjects with MCA PI < 5th percentile in order to understand the possible implications of BDNF in this group.

Foetal umbilical cord brain-derived neurotrophic factor (BDNF) levels in pregnancy with gestational diabetes mellitus

The aim of our study was to investigate whether gestational diabetes mellitus (GDM) affects brain-derived neurotrophic factor (BDNF) levels in foetal umbilical cord blood. A total of 96 participants were divided into a GDM group (n = 43) and a non-diabetic control group (n = 53). Cord blood samples of approximately 5 cc were taken immediately after the foetal umbilical cord was clamped during delivery in order to determine BDNF levels. While the mean age, body mass index, birth weight, rate of caesarean delivery, rate of infant macrosomia, and neonatal intensive care unit admission of women with GDM were significantly higher compared to the non-diabetic control group (p < .05), pregnancy complications were comparable between the groups (p > .05). Although no significant differences were noted between the groups with respect to cord blood BDNF levels (0.79 ± 0.37 ng/ml vs. 0.69 ± 017 ng/ml, p = .122), cord blood BDNF values were higher in female infants compared to male infants (0.85 ± 0.33 ng/ml vs. 0.66 ± 0.23 ng/ml, p = .001) and in patients using insulin compared to those not using insulin in the GDM group (0.78 ± 0.14 ng/ml vs. 0.62 ± 0.09 ng/ml, p < .001). This study found that GDM has no effect on cord blood BDNF levels. More in-depth studies with larger series are needed to validate the results of the present study. Impact statement What is already known on this subject? Gestational diabetes mellitus (GDM) negatively affects the foetal neurodevelopment due to inflammation and oxidative stress caused by hyperglycaemia. Brain-derived neurotrophic factor (BDNF) expression has been shown to modulate oxidative stress and inflammation, and there may be a relationship between varying BDNF concentrations and GDM. What do the results of this study add? Our study showed that no significant differences were noted between the groups with respect to cord blood BDNF levels, cord blood BDNF values were higher in female infants compared to male infants, and in patients using insulin compared to those not using insulin in the GDM group. What are the implications of these findings for clinical practice and/or further research? GDM negatively affects the foetal neurodevelopment due to inflammation and oxidative stress caused by hyperglycaemia. BDNF expression has also been shown to modulate oxidative stress and inflammation, and there may be a relationship between varying BDNF concentrations and GDM. The association between BDNF expression and GDM has not been clearly elucidated in the literature. More in-depth studies with larger series are needed to determine this relationship.

Structural and functional brain alterations in patients with myasthenia gravis.

Myasthenia gravis is an autoimmune disease affecting neuromuscular transmission and causing skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described. However, little is known about myasthenia gravis-related reorganization of the brain. In this study, we thus investigated the structural and functional brain changes in myasthenia gravis patients. Eleven myasthenia gravis patients (age: 70.64 ± 9.27; 11 males) were compared to age-, sex- and education-matched healthy controls (age: 70.18 ± 8.98; 11 males). Most of the patients (n = 10, 0.91%) received cholinesterase inhibitors. Structural brain changes were determined by applying voxel-based morphometry using high-resolution T1-weighted sequences. Functional brain changes were assessed with a neuropsychological test battery (including attention, memory and executive functions), a spatial orientation task and brain-derived neurotrophic factor blood levels. Myasthenia gravis patients showed significant grey matter volume reductions in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. Furthermore, myasthenia gravis patients showed significantly lower performance in executive functions, working memory (Spatial Span, P = 0.034, d = 1.466), verbal episodic memory (P = 0.003, d = 1.468) and somatosensory-related spatial orientation (Triangle Completion Test, P = 0.003, d = 1.200). Additionally, serum brain-derived neurotrophic factor levels were significantly higher in myasthenia gravis patients (P = 0.001, d = 2.040). Our results indicate that myasthenia gravis is associated with structural and functional brain alterations. Especially the grey matter volume changes in the cingulate gyrus and the inferior parietal lobe could be associated with cognitive deficits in memory and executive functions. Furthermore, deficits in somatosensory-related spatial orientation could be associated with the lower volumes in the inferior parietal lobe. Future research is needed to replicate these findings independently in a larger sample and to investigate the underlying mechanisms in more detail.

Efficacy of Whole-Body Vibration Training on Brain-Derived Neurotrophic Factor, Clinical and Functional Outcomes, and Quality of Life in Women with Fibromyalgia Syndrome: A Randomized Controlled Trial.

This study aimed to investigate the efficacy of whole-body vibration training (WBVT) on blood brain-derived neurotrophic factor (BDNF) levels and determine the clinical and functional outcomes in patients with fibromyalgia syndrome (FMS). Thirty-two women with FMS were randomized into an intervention group (IG), receiving 6 weeks of WBVT, or a control group (CG) with no intervention. The outcomes at the baseline and follow-up in both groups included blood BDNF levels, sit-to-stand test (STS), 6-minute walk test (6MWT), Fibromyalgia Impact Questionnaire (FIQ), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), and visual analogue scale (VAS). WBVT resulted in a group-by-time interaction effect. Thus, after the intervention time, the IG had increased blood BDNF levels (p=0.045), a higher number of repetitions on the STS test (p=0.011), and increased walking distance on the 6MWT (p=0.010), compared to CG. Moreover, there was a reduction in the scores of the FIQ (p=0.001), the PSQI (p=0.001), the BDI (p=0.017), and pain assessed using VAS (p=0.008) in IG. The results demonstrate that WBVT promotes an increase in blood BDNF levels, with concomitant improvement in lower limb muscle strength, aerobic capacity, clinical symptoms, and quality of life in women with FMS. This trial is registered with Brazilian Clinical Trials Registry (REBEC; RBR-38nbbx) (https://ensaiosclinicos.gov.br/rg/RBR-38nbbx).

Elevated levels of cortisol, brain-derived neurotropic factor and tissue plasminogen activator in male children with autism spectrum disorder.

Several studies demonstrated biological effects of cortisol, brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA) on human metabolism and central nervous system. Our study investigated the serum levels of tPA along with BDNF and cortisol in children with autism spectrum disorder (ASD). Thirty three male children with ASD ranging in age from 2 to 15 years were selected for the study group and 27 age-matched healthy male children were selected for the control group. The ASD severity was determined by the score on the Autism Behavior Checklist (ABC). The mean cortisol levels for the study group and the control group were 79.1 ± 30.2ng/ml and 60.0 ± 25.1ng/ml, respectively. The mean BDNF levels for the study group and the control group were 5.9 ± 2.8ng/ml and 3.7 ± 1.8ng/ml, respectively. The mean tPA levels for the study group and the control group were 32.9 ± 18.5ng/ml and 25.5 ± 15.1ng/ml, respectively. Cortisol, BDNF and tPA levels were significantly higher in the study group compared to the control group (p < 0.001). There was no statistically significant effect in terms of age, ABC total and subscale scores on serum cortisol, BDNF and tPA levels in the study group (p > 0.05). It may be suggested that elevations may indicate a role in the pathogenesis of ASD or it may be the case that ASD may alter the levels or pathways of these metabolic factors. LAY SUMMARY: The underlying mechanism or a specific metabolic target relevant to autism spectrum disorder (ASD) has not yet been identified. Cortisol, brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA) have biological effects on neuroplasticity but little is known about the role of cortisol and tPA-BDNF pathway in ASD. In the present study focused on male children with ASD, we have found higher blood levels of cortisol, BDNF and tPA than their healthy peers. This is the first clinical study to evaluate the serum tPA levels along with BDNF and cortisol in ASD. The results suggest that several neurotrophic and other related markers should be born in mind while examining children with ASD.

Plasma Levels of Brain-Derived Neurotrophic Factor and S100B in Relation to Antidepressant Response to Ketamine.

BackgroundEvidence demonstrates that brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100B) have a pivotal role in the pathogenesis of major depressive disorder (MDD) and they are proposed as predictors of antidepressant response. Ketamine produces rapid antidepressant effects in MDD and pre-clinical studies suggest the necessity of increased BDNF levels for the antidepressant action of ketamine. However, studies observing the change of blood BDNF levels after ketamine intervention are inconsistent and studies about the role of plasma S100B in ketamine administration in MDD patients are lacking.MethodWe evaluated mature BDNF (mBDNF), S100B levels in plasma and their associations with depression severity in 30 Selective Serotonin Reuptake Inhibitor (SSRI)-resistant MDD patients enrolled in a randomized controlled trial of ketamine compared (n = 20) to a placebo (n = 10) control (saline). Severity of depression was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS).ResultsPlasma mBDNF and S100B were not significantly changed after 1–2 days of single ketamine compared to placebo. Plasma mBDNF and S100B levels did not significantly differ in responders compared to non-responders of ketamine treatment. The change of plasma mBDNF levels was positively correlated with the improvement of MADRS score after 1–2 weeks of open-label ketamine treatment (rho = 0.495, p = 0.031), though this change did not survive correction for multiple comparisons.ConclusionThese findings do not support the hypothesis that ketamine treatment increases BDNF plasma levels in MDD patients. No effect of ketamine treatment on S100B plasma levels was seen.

Cognitive Dysfunction in a Mouse Model of Cerebral Ischemia Influences Salivary Metabolomics.

Vascular dementia, caused by cerebrovascular disease, is associated with cognitive impairment and reduced hippocampal metabolite levels. Specifically, cognitive impairment can be induced by decreased hippocampal brain-derived neurotrophic factor (BDNF) expression. The development of low or non-invasive biomarkers to characterize these diseases is an urgent task. Disturbance of metabolic pathways has been frequently observed in cognitive impairment, and salivary molecules also showed the potentials to reflect cognitive impairment. Therefore, we evaluated salivary metabolic profiles associated with altered hippocampal BDNF expression levels in a cerebral ischemia mouse model using metabolomic analyses. The effect of tacrine (a cholinesterase inhibitor) administration was also examined. The arteries of ICR mice were occluded with aneurysm clips to generate the cerebral ischemia model. Learning and memory performance was assessed using the elevated plus maze (EPM) test. Hippocampal and blood BDNF levels were quantified using an enzyme-linked immunosorbent assay. Glutamate decarboxylase 1 (GAD1) mRNA expression, is associated with cognitive impairment, was quantified by a real-time polymerase chain reaction. The EPM test revealed impaired spatial working memory in the cerebral ischemia mouse model; tacrine administration ameliorated this memory impairment. Cerebral ischemia suppressed GAD1 expression by decreasing hippocampal BDNF expression. In total, seven salivary metabolites, such as trimethylamine N-oxide and putrescine, were changed by cognitive impairment and tacrine administration. Our data suggest that salivary metabolite patterns were associated with cognitive function.

Association of neonatal blood levels of brain-derived neurotrophic factor with development of autism spectrum disorder: a systematic review and meta-analysis.

Our goal was to evaluate the association between neonatal blood brain-derived neurotrophic factor (BDNF) level and autism spectrum disorder (ASD) diagnosis later in life. MEDLINE and Web of Science databases were searched from inception until September 16, 2020. Reference lists of all relevant articles also were reviewed. Mean blood BDNF concentrations, standard deviations, sample sizes, and other data needed for calculation of effect sizes were extracted by two independent investigators. The quality of the included studies was appraised using the Newcastle-Ottawa Scale for case-control studies. Data were pooled using the random-effects model. Five case-control studies involving 1341 cases and 3395 controls were included in the meta-analysis. The meta-analysis of all included studies showed no significant difference in blood BDNF levels between neonates diagnosed with ASD later in life and healthy controls [standardized mean difference (SMD) = 0.261; 95% confidence interval (CI) - 0.052 to 0.573; P = 0.102], with high level of heterogeneity (Q = 64.346; I2 = 93.784; P < 0.001). A subgroup analysis by assay type showed decreased blood BDNF levels in ASDs compared to controls (SMD = - 0.070; 95% CI - 0.114 to - 0.026; P = 0.002), with high level of homogeneity (Q = 0.894; I2 = 0.000; P = 0.827). No evidence of publication bias was observed. Neonates diagnosed with ASD later in life have decreased blood levels of BDNF measured by double-antibody immunoassay. More studies are warranted to facilitate a more robust conclusion.

Effects of Regulatory Resistance Exercise on Brain Neuroplasticity Factors in Prediabetic Elderly

PURPOSE: The purpose of this study was to determine whether regulatory resistance exercise is as effective as aerobic training at improving the blood levels of brain-derived neurotrophic factor (BDNF), and nerve growth factors (NGF) as well as Cathepsin B, which are major factors contributing to the regulation of glucose metabolism and neuroplasticity, in prediabetic elderly.METHODS:Among the elderly aged 65 years or older who attended the B welfare center in C city, 16 patients who had no disease and had HbA1c of 5.7-6.4% were randomly assigned into either control group (CO, n=8, age 69.12±2.07 years) and resistance exercise group (RE, n=8, 71.25±1.69 years). Both groups were exercised three times a week for 12 weeks with the exercise intensity of 200- 250 kcal consumed Body composition and basic physical fitness tests were measured at baseline and at week 12. Blood levels of BDNF, NGF and Cathepsin B were also analyzed by using glucose metabolism factor and enzyme immunoassay.RESULTS:As a result, there were no significant differences in all body composition in both CO and RE. In addition, there were no statistically significant differences in all variables of the glycolysis factor. The blood levels of BDNF and NGF were significantly increased after the 12 weeks exercise program in the RE compared with the CO (p&lt;.05).CONCLUSIONS: Based on these results, regular resistance exercise seems to be effective in increasing the brain neuroplasticity factors BDNF and NGF in prediabetic elderly. Depending on the prediabetes stage or the period of stay in the diabetic stage, further study is needed after considering the exercise period and intensity.

Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer’s disease: Possible role of BDNF and oxidative stress

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique which is increasingly used for cognitive impairment in Alzheimer’s Disease (AD). Although rTMS has been shown to modify Brain-Derived Neurotrophic Factor (BDNF) and oxidative stress levels in many neurological and psychiatric diseases, there is still no study evaluating the relationship between memory performance, BDNF, oxidative stress, and resting brain connectivity following rTMS in Alzheimer's patients. Furthermore, there are increasing clinical data showing that the stimulation of strategic brain regions may lead to more robust improvements in memory functions compared to conventional rTMS. In this study, we aimed to evaluate the possible disease-modifying effects of rTMS on the lateral parietal cortex in AD patients who have the highest connectivity with the hippocampus. To fill the mentioned research gaps, we have evaluated the relationships between resting-state Functional Magnetic Resonance Imaging (fMRI), cognitive scores, blood BDNF levels, and total oxidative/antioxidant status to explain the therapeutic and potential disease-modifying effects of rTMS which has been applied at 20 Hz frequencies for two weeks. Our results showed significantly increased visual recognition memory functions and clock drawing test scores which were associated with elevated peripheral BDNF levels, and decreased oxidant status after two weeks of left lateral parietal TMS stimulation. Clinically our findings suggest that the left parietal region targeted rTMS application leads to significant improvement in familiarity-based cognition associated with the network connections between the left parietal region and the hippocampus.

Blood Brain-Derived Neurotrophic Factor (BDNF) and Major Depression: Do We Have a Translational Perspective?

Major depressive disorder (MDD) affects millions of people worldwide and is a leading cause of disability. Several theories have been proposed to explain its pathological mechanisms, and the “neurotrophin hypothesis of depression” involves one of the most relevant pathways. Brain-derived neurotrophic factor (BDNF) is an important neurotrophin, and it has been extensively investigated in both experimental models and clinical studies of MDD. Robust empirical findings have indicated an association between increased BDNF gene expression and peripheral concentration with improved neuronal plasticity and neurogenesis. Additionally, several studies have indicated the blunt expression of BDNF in carriers of the Val66Met gene polymorphism and lower blood BDNF (serum or plasma) levels in depressed individuals. Clinical trials have yielded mixed results with different treatment options, peripheral blood BDNF measurement techniques, and time of observation. Previous meta-analyses of MDD treatment have indicated that antidepressants and electroconvulsive therapy showed higher levels of blood BDNF after treatment but not with physical exercise, psychotherapy, or direct current stimulation. Moreover, the rapid-acting antidepressant ketamine has presented an early increase in blood BDNF concentration. Although evidence has pointed to increased levels of BDNF after antidepressant therapy, several factors, such as heterogeneous results, low sample size, publication bias, and different BDNF measurements (serum or plasma), pose a challenge in the interpretation of the relation between peripheral blood BDNF and MDD. These potential gaps in the literature have not been properly addressed in previous narrative reviews. In this review, current evidence regarding BDNF function, genetics and epigenetics, expression, and results from clinical trials is summarized, putting the literature into a translational perspective on MDD. In general, blood BDNF cannot be recommended for use as a biomarker in clinical practice. Moreover, future studies should expand the evidence with larger samples, use the serum or serum: whole blood concentration of BDNF as a more accurate measure of peripheral BDNF, and compare its change upon different treatment modalities of MDD.

Ninjin'yoeito Alleviates Neuropathic Pain Induced by Chronic Constriction Injury in Rats.

Kampo medicines are frequently used empirically to treat pain in clinical practice. Ninjin'yoeito (NYT), which is associated with few adverse effects, is often used to treat the elderly, but has not yet been examined in detail. We herein investigated the effects of NYT, at 500 and 1,000 mg/kg p.o. (NYT500/NYT1000 group) in single and repeated administrations for 14 days, on pain in rats with peripheral neuropathy induced by loose ligation of the sciatic nerve (chronic constriction injury: CCI). Untreated CCI rats given distilled water were used as a control group. To assess induced pain, the pain threshold was measured using the von Frey test. To evaluate spontaneous pain, the ground-contact area of the paw with neuropathic pain was measured using the Dynamic Weight Bearing test. Serum samples were collected after the test to elucidate the mechanism of action of NYT, and brain-derived neurotrophic factor (BDNF) and corticosterone protein levels, which have been reported to change due to chronic pain, were analyzed. After single administration of NYT, the pain threshold rose in the NYT500 and NYT1000 groups. The pain threshold tended to rise on day 14 of repeated administration in the NYT500 group (p = 0.08) and it significantly rose at NYT1000 group (p < 0.05) compared to Control group. In addition, the foot contact area increased (p = 0.09). Therefore, CCI-induced pain was significantly remitted and spontaneous pain was remitted after repeated administration of NYT. Serum BDNF levels were higher in untreated CCI rats than in normal rats (p = 0.05), but decreased after the repeated administration of NYT (NYT1000, p = 0.15), while serum corticosterone levels were lower (p = 0.12) than those in normal rats and increased after the repeated administration of NYT (NYT1000, p = 0.07). The blood BDNF level has been suggested to influence pain intensity. The findings demonstrated NYT effectively treats neuropathic pain, suggesting that a NYT-induced decrease in blood BDNF contributed to the mechanism of pain relief. In addition, the variation of corticosterone was observed, suggesting that normalization of responsiveness to stress by NYT contributed to the pain relief.

The Effect of a Portable Electrical Muscle Stimulation on Brain-Derived Neurotrophic Factor in Elderly People: Three Case Studies.

Brain-derived neurotrophic factor (BDNF), which plays an important role in cognitive and nerve function, is released from skeletal muscle cells into the blood by muscle contractions and/or electrical muscle stimulation (EMS). However, the influence of EMS administered by a portable device on BDNF is unclear. The purpose of this case report was to quantify the influence of EMS administered by a portable device on BDNF and physical function. Three elderly people (age, 69.7 ± 1.5 years) were included in the present study. The participants used a portable EMS device to stimulate the bilateral quadriceps muscles for 8 weeks (23 min for 5 days/week). To determine the effects of EMS, the following parameters were assessed at baseline, 8 weeks, and 12 weeks (follow-up): knee extensor strength, muscle mass of the lower limb, Berg balance score, and blood BDNF level. All outcomes improved after the EMS intervention, but the improvements did not persist for 12 weeks. These findings suggest that portable EMS is potentially useful for improving the blood BDNF level and physical function.

The BDNF-Increasing Allele is Associated With Increased Proportion of Fast-Twitch Muscle Fibers, Handgrip Strength, and Power Athlete Status.

Guilherme, JPLF, Semenova, EA, Borisov, OV, Kostryukova, ES, Vepkhvadze, TF, Lysenko, EA, Andryushchenko, ON, Andryushchenko, LB, Lednev, EM, Larin, AK, Bondareva, EA, Generozov, EV, and Ahmetov, II. The BDNF-increasing allele is associated with increased proportion of fast-twitch muscle fibers, handgrip strength, and power athlete status. J Strength Cond Res 36(7): 1884-1889, 2022-The brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and formation of regenerated myofibers following injury or damage. A recent study suggested that the BDNF overexpression increases the proportion of fast-twitch muscle fibers, while the BDNF deletion promotes a fast-to-slow transition. The purpose of this study was to evaluate the association between the BDNF gene rs10501089 polymorphism (associated with blood BDNF levels), muscle fiber composition, and power athlete status. Muscle fiber composition was determined in 164 physically active individuals (113 men, 51 women). BDNF genotype and allele frequencies were compared between 508 Russian power athletes, 178 endurance athletes, and 190 controls. We found that carriers of the minor A-allele (the BDNF-increasing allele) had significantly higher percentage of fast-twitch muscle fibers than individuals homozygous for the G-allele (males: 64.3 [7.8] vs. 50.3 [15.8]%, p = 0.0015; all subjects: 64.1 ± 7.9 vs. 49.6 ± 14.7%, p = 0.0002). Furthermore, the A-allele was associated (p = 0.036) with greater handgrip strength in a sub-group of physically active subjects (n = 83) and over-represented in power athletes compared with controls (7.7 vs. 2.4%, p = 0.0001). The presence of the A-allele (i.e., AA+AG genotypes) rather than GG genotype increased the odds ratio of being a power athlete compared with controls (odds ratio [OR]: 3.43, p = 0.00071) or endurance athletes (OR: 2.36, p = 0.0081). In conclusion, the rs10501089 A-allele is associated with increased proportion of fast-twitch muscle fibers and greater handgrip strength, and these may explain, in part, the association between the AA/AG genotypes and power athlete status.

Peripheral blood levels of brain-derived neurotrophic factor in patients with post-traumatic stress disorder (PTSD): A systematic review and meta-analysis.

Brain-derived neurotrophic factor (BDNF) plays a crucial role in the survival, differentiation, growth, and plasticity of the central nervous system (CNS). Post-traumatic stress disorder (PTSD) is a complex syndrome that affects CNS function. Evidence indicates that changes in peripheral levels of BDNF may interfere with stress. However, the results are mixed. This study investigates whether blood levels of BDNF in patients with post-traumatic stress disorder (PTSD) are different. We conducted a systematic search in the major electronic medical databases from inception through September 2019 and identified Observational studies that measured serum levels of BDNF in patients with PTSD compared to controls without PTSD. 20 studies were eligible to be included in the present meta-analysis. Subjects with PTSD (n = 909) showed lower BDNF levels compared to Non-PTSD controls (n = 1679) (SMD = 0.52; 95% confidence interval: 0.18 to 0.85). Subgroup meta-analyses confirmed higher levels of BDNF in patients with PTSD compared to non-PTSD controls in plasma, not serum, and in studies that used sandwich ELISA, not ELISA, for BDNF measurement. Meta-regressions showed no significant effect of age, gender, NOS, and sample size. PTSD patients had increased serum BDNF levels compared to healthy controls. Our finding of higher BDNF levels in patients with PTSD supports the notion that PTSD is a neuroplastic disorder.