Brain-derived Neurotrophic Factor Concentrations Research Articles

THE ROLE OF BIOCHEMICAL BIOMARKERS FOR NEURONAL ACTIVITY AND CLINICAL NEUROPSYCHOLOGICAL TESTS IN PATIENTS WITH CAROTID STENTING

Objective: The application of carotid stenting is rising. We need biomarkers, which would guide us and help in the assessment of its effectiveness regarding brain blood flow and cognition. Potential candidate biomarkers are the markers for neuronal activity Brain Derived Neurotrophic Factor (BDNF) and Neural Growth Factor (NGF). Their serum concentration is correlated with brain hemodynamics and function. Design and method: We included 78 patients: 39 with hemodynamically significant carotid stenoses and 39 controls - without. All underwent ultrasound diagnostics and ELISA test of BDNF and NGF serum concentrations. The biomarkers for neural activity in patients with significant carotid stenoses, were tested at 3 phases: before (n34), 24 h. post (n22) and at least 1 month after stenting (n18). Cognitive functions were assessed with MMSE and MoCA. On their basis the patients were classified as having or not potential mild cognitive impairment (MCI) Statistical analysis was done with SPSS 19(IBM), p < 0.05, CI 95%. Results: There was a significant difference in the BDNF concentration before and after carotid stenting (p < 0.0001); in BDNF [p = 0.001, CI (-5.11- -1.44)] and NGF [p = 0.049, CI (0.64–347.75)] between patients with significant stenoses/stenting and controls. Periprocedural hypotension, stroke history and MCI did not influence biomarkers concentrations. Correlation analysis showed intermediate positive correlation between systolic, diastolic, pulse pressure and biomarkers at a certain time of sampling. This association was proven for the systolic blood pressure by the regression analysis too. The mean values of BDNF after stenting raised and for NGF lowered after carotid stenting. Conclusions: A larger sample is needed to prove further our results, namely: 1. Arterial blood pressure is an important factor for BDNF and NGF concentrations; 2. The correlation between these markers and interventional treatment may be not linear; 3. There are significant differences in the serum concentrations of biomarkers for neural activity between patients with and without significant carotid stenoses. Research Grant 2020 from Medical University Sofia, Bulgaria, contract 133/24.06.2020

CAN WE USE NEUROTROPHINS FOR CAROTID PLAQUE VULNERABILITY ASSESSMENT – IVUS VH CASE SERIES

Objective: Defining carotid atherosclerotic plaque vulnerability is problematic. The combination between imaging and biomarkers may be of practical significance for future assessment of extracranial stenoses. Brain derived neurotrophic factor (BDNF) and neuronal growth factor (NGF) are neurotrophins. There are some studies, which suggest association between endothelial dysfunction and circulating BDNF, impaired neurotrophins’ endothelial secretion in atherosclerosis and correlation between BDNF concentration and Agatson’s score, as well as coronary plaque vulnerability. Neurotrophins also play important role in cerebral functioning. Their role in carotid atherosclerosis is not known. Design and method: We share the results of 13 patients with angiographically significant carotid stenoses. The plaque morphology was assessed with IVUS VH and we evaluated their serum BDNF and NGF concertation. All the patients were without coronary artery disease or fully revascularized, as well as without significant or symptomatic peripheral artery disease. We had the results for BDNF and NGF from a reference group without any atherosclerotic disease. SPSS (IBM) was used for the statistical analysis, p < 0.05, CI 95%. Results: The patients with significant carotid stenoses had lower mean BDNF values than the reference group. There was correlation between luminal diameter and BDNF (p = 0.049; r = -0.605), total Ca2+ area (mm2) and BDNF (r = 0.681, p = 0.021), Proximal Ca2+area and BDNF (p = 0.007, r = 0.784), Necrotic core % in the proximal plaque area and NGF (r = 0.891, p = 0.001) Conclusions: BDNF concentration was negatively correlated with the maximal values for minimal luminal diameter and positively with total Ca2+ plaque area, t.i. with plaque stability. We found positive correlation with necrotic core % and NGF values. This case series is small, and a much larger sample is needed to define precisely any association. Nevertheless, this is a beginning of the study for the potential role of neurotrophins in carotid plaque morphology, either by their local endothelial secretion or by modification of their central secretion from the altered cerebral hemodynamics. They may be both markers and factors for carotid plaque vulnerability. The work was partially funded by a Research GRANT 2020 number 133 from Medical University Sofia, Bulgaria.

BDNF-AAV has protective effects on morphine-induced conditioned place preference through BDNF, TrkB, and CREB concentration changes in the VTA and NAc

Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that promotes the survival and protection of neurons in many disorders. The potential protective effect of BDNF and its mechanisms on morphine addiction are unclear. In this study, morphine-induced conditioned place preference (CPP) in mice was used to show the effect of BDNF on rewarding behavior. Western blot assays were used to determine the changes caused by BDNF, for example, changes in total BDNF, tropomyosin-related kinase receptor B (TrkB), and cAMP response element binding protein (CREB) in the ventral tegmental area (VTA) and nucleus accumbens (NAc). The results showed that the BDNF-adeno-associated viral vector (BDNF-AAV) injected in the VTA, attenuated morphine-induced CPP with synergistic changes in BDNF/TrkB/CREB concentrations in the VTA and NAc in the CPP acquisition and recurrence phases; however, the attenuation was lower in the extinction phase, with different changes in molecules downstream of the BDNF.

Activation of BDNF- and VEGF-mediated Neuroprotection by Treadmill Exercise Training in Experimental Stroke.

Early treatment of ischemic stroke is one of the most effective ways to reduce brains' cell death and promote functional recovery. This study was designed to examine the effect of aerobic exercise on post ischemia/reperfusion injury on concentration and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) after inducing a neuronal loss in CA1 region of hippocampus in Male Wistar rats. Three experimental groups including sham(S), ischemia/reperfusion-control (IRC) and ischemia/reperfusion exercise (IRE) were used for this purpose. The rats in the IRE group received a bilateral carotid artery occlusion treatment. They ran for 45 minutes on a treadmill five days per week for eight consecutive weeks. Cresyl violet (Nissl), Hematoxylin (H & E) and Eosin staining procedure were used to determine the extent of damage. A ladder rung walking task was used to assess the functional impairments and recovery after the ischemic lesion. ELISA and immunohistochemistry method were employed to measure BDNF and VEGF protein expressions. The result showed that the brain ischemia/reperfusion condition increased the cell death in hippocampal CA1 neurons and impaired motor performance on the ladder rung task whereas the aerobic exercise program significantly decreased the brain cell's death and improved motor skill performance. It was concluded that ischemic brain lesion decreased the BDNF and VEGF expression. It seems that the aerobic exercise following the ischemia/reperfusion potentially promotes neuroprotective mechanisms and neuronal repair and survival mediated partly by BDNF and other pathways.

The influencing factors of cognitive impairment in patients with silicosis

Objective: To explore the influencing factors of cognitive impairment in patients with silicosis, and to analyze the effect of brain-derived neurotrophic factor (BDNF) on cognitive function. Methods: In March 2021, 484 silicosis patients from April 2018 to April 2020 were included in the study. The Montreal Cognitive Assessment Scale of Chinese version was used to evaluate their cognitive function, and they were divided into the cognitive impairment group (n=282) and the non cognitive impairment group (n=202) , another 30 healthy persons from body check were served as control group. The concentrations of BDNF were compared between the three groups. And the receiver operating characteristic (ROC) curve was drawed to analyze the value of BDNF in predicting cognitive impairment in silicosis patients. And the logistic regression analysis was used to explore the risk factors of cognitive impairment. Results: The incidence of cognitive impairment in silicosis patients was 58.26% (282/484) . The level of BDNF in the cognitive impairment group[ (10.32±2.11) mg/L] was significantly lower than that in the non cognitive impairment group[ (13.43±3.45) mg/L] (t=-12.27, P<0.001) . The results of ROC curve analysis showed that the area unde the curve of BDNF in predicting cognitive impairment of silicosis patients was 0.763 (95%CI: 0.613-0.874, P=0.024) , the cut off value was 10 mg/L, the sensitivity was 0.88, and the specificity was 0.84. Logistic regression analysis showed that the level of BDNF (≤10 mg/L) , age (≥65 years old) , course of disease (≥5 years) and diabetes mellitus were the risk factors of cognitive impairment in silicosis patients (OR=2.346, 95%CI: 1.654-3.103; OR=1.757, 95%CI: 1.214-1.998; OR=1.346, 95%CI: 1.112-1.564; OR=1.165, 95%CI: 1.102-1.542, P=0.001, 0.012, 0.027, 0.036) . Conclusion: BDNF may be one of the indicator to predict the risk of cognitive impairment in patients with silicosis.

Brain-Derived Neurotrophic Factor Is an Important Therapeutic Factor in Mesenchymal Stem Cell Secretions for Treatment of Traumatic Peripheral Pelvic Injuries.

Traumatic neuromuscular injury to the pudendal nerve and urethra during childbirth does not regenerate well and contributes to stress urinary incontinence in women. Mesenchymal stem cells (MSCs) can improve neuroregeneration via their secretions, or secretome, which includes brain-derived neurotrophic factor (BDNF). In this study, we investigated whether BDNF is a key factor in the secretome of MSCs for the facilitation of functional recovery following a dual simulated childbirth injury. BDNF knockdown (KD) MSCs were created using an anti-BDNF shRNA lentivirus vector. A scrambled sequence was used as a transduction control (scrambled). Cells were cultured for 24 h before media was concentrated 50x to create concentrated conditioned media (CCM) containing MSC secretome. CCM of unmanipulated MSCs was screened for high BDNF expression (high BDNF CCM). Concentrated control media (CM) was created by concentrating media not conditioned by cells. Female Sprague-Dawley rats underwent bilateral pudendal nerve crush and vaginal distension (Injury) or sham injury. One hour and 1 week after injury, sham injured rats received CM, and injured rats received CM, high BDNF CCM, KD CCM, or scrambled CCM (300 μl intraperitoneally). Three weeks after injury, rats underwent leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings. The urethra and pudendal nerve were harvested for anatomical assessment. ANOVA followed by the Student-Newman-Keuls test determined significant differences between groups (p < 0.05). BDNF KD CCM had significantly decreased BDNF concentration compared to scrambled CCM, while the concentration in high BDNF CCM was significantly increased. LPP was significantly decreased in CM and KD CCM treated animals compared to sham injury, but not with scrambled or high BDNF CCM. PNSBP firing rate showed a significant decrease with CM treatment compared to sham injury. Neuromuscular junctions in the urethral sphincter in KD CCM, scrambled CCM, and high BDNF CCM were healthier than CM treated rats. While anatomical and nerve function tests demonstrate regeneration of the pudendal nerve with any CCM treatment, LPP results suggest it takes longer to recover continence with reduced BDNF in CCM. BDNF in MSC CCM is an important factor for the acceleration of recovery from a dual nerve and muscle injury.

Selective activation and down-regulation of Trk receptors by neurotrophins in human neurons co-expressing TrkB and TrkC.

In the central nervous system, most neurons co‐express TrkB and TrkC, the tyrosine kinase receptors for brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT3). As NT3 can also activate TrkB, it has been difficult to understand how NT3 and TrkC can exert unique roles in the assembly of neuronal circuits. Using neurons differentiated from human embryonic stem cells expressing both TrkB and TrkC, we compared Trk activation by BDNF and NT3. To avoid the complications resulting from TrkB activation by NT3, we also generated neurons from stem cells engineered to lack TrkB. We found that NT3 activates TrkC at concentrations lower than those of BDNF needed to activate TrkB. Downstream of Trk activation, the changes in gene expression caused by TrkC activation were found to be similar to those resulting from TrkB activation by BDNF, including a number of genes involved in synaptic plasticity. At high NT3 concentrations, receptor selectivity was lost as a result of TrkB activation. In addition, TrkC was down‐regulated, as was also the case with TrkB at high BDNF concentrations. By contrast, receptor selectivity as well as reactivation were preserved when neurons were exposed to low neurotrophin concentrations. These results indicate that the selectivity of NT3/TrkC signalling can be explained by the ability of NT3 to activate TrkC at concentrations lower than those needed to activate TrkB. They also suggest that in a therapeutic perspective, the dosage of Trk receptor agonists will need to be taken into account if prolonged receptor activation is to be achieved.

Hippocampal Volume and Plasma Brain-Derived Neurotrophic Factor Levels in Patients With Depression and Healthy Controls.

The aim of the present study was to investigate associations between hippocampal subfield volumes and plasma levels of brain-derived neurotrophic factor (BDNF) in patients experiencing a first episode of major depression (MD) (n = 30) as compared to healthy controls (HC) (n = 49). Covariate-adjusted linear regression was performed to compare the MD and healthy groups, adjusting for age, sex, and total estimated intracranial volume. We demonstrated that there were no differences in total hippocampal volume between the MD and HC groups. However, the volumes of the hippocampus-amygdala-transition-area (HATA) on the left side of the brain as well as the parasubiculum, presubiculum, and fimbria on the right side were statistically significantly smaller in the MD group than in the HC group. Furthermore, the volume of the hippocampal fissure on the right side was statistically significantly smaller in the HC group than in the MD group. In the MD group, we found a positive linear correlation between hippocampal volume and plasma BDNF concentrations in the CA4 area on the left side (p = 0.043). In contrast, in the HC group, we found a negative linear correlation between parasubiculum volume on the right side and plasma BDNF concentrations (p = 0.04). These results suggest that some hippocampal subfields may already be atrophic at the start of MD. In addition, our findings suggest that the sensitivity of the right parasubiculum region to BDNF may differ between MD and HC groups. These findings guide future research directions and, if confirmed, may ultimately inform medical guidelines.

Salivary Neurotrophins Brain-Derived Neurotrophic Factor and Nerve Growth Factor Associated with Childhood Obesity: A Multiplex Magnetic Luminescence Analysis.

Obesity is linked with higher inflammatory markers and is characterized by chronic low-grade inflammation. Neurotrophins brain-derived neurotrophic factor (BDNF) and β-nerve growth factor (β-NGF), in addition to their neuronal functions, act on several immune cells and have been recently designated as metabokines due to their regulatory role in energy homeostasis and food intake. The current study evaluates the salivary BDNF and β-NGF and their association with anthropometric measurement, blood pressure, and salivary insulin in children. Anthropometric measurements and saliva samples were obtained from 76 children, aged 6–10 years. Multiplex analysis was carried out for the salivary analysis of BDNF, NGF, and insulin by human magnetic Luminex performance assay. Statistical analysis was performed to analyze the best fit diagnostic value for biomarkers and the relationship of the neurotrophic levels of BDNF and NGF with obesity measures and blood pressure. Salivary BDNF and β-NGF showed a significantly higher concentration in obese children than normal-weight children. Both neurotrophins are positively associated with obesity anthropometric measures, blood pressure, and salivary insulin. Multinominal regression analysis reported a significant association between salivary BDNF, β-NGF, insulin, and systolic pressure adjusted for age, gender, income, and maternal education. The salivary concentration of BDNF and NGF was higher in obese children, and it is positively associated with anthropometric measures, suggesting that neurotrophins can be used as a non-invasive predictor of obesity-related complications in children.

Neurotrophic Factors in Experimental Cerebral Acanthamoebiasis.

To date, no studies have addressed the role of neurotrophins (NTs) in Acanthamoeba spp. infections in the brain. Thus, to clarify the role of NTs in the cerebral cortex and hippocampus during experimental acanthamoebiasis in relation to the host immune status, the purpose of this study was to determine whether Acanthamoeba spp. may affect the concentration of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) in brain structures. Our results suggest that at the beginning of infection in immunocompetent hosts, BDNF and NT-3 may reflect an endogenous attempt at neuroprotection against Acanthamoeba spp. infection. We also observed a pro-inflammatory effect of NGF during acanthamoebiasis in immunosuppressed hosts. This may provide important information for understanding the development of cerebral acanthamoebiasis related to the immunological status of the host. However, the pathogenesis of brain acanthamoebiasis is still poorly understood and documented and, therefore, requires further research.

Explore the Mechanism of β-Asarone on Improving Cognitive Dysfunction in Rats with Diabetic Encephalopathy.

Background:The number of people with diabetes is increasing, and many patients have significantly impaired cognitive function. For patients with diabetic encephalopathy (DE), simply lowering blood sugar does not improve learning and memory. Studies have shown that β-asarone can significantly improve cognitive impairment in patients with DE, but the specific mechanism of action is unclear.Objective:This experiment hopes to use a variety of experimental methods to clarify the protective effect and mechanism of β-asarone on brain neurons during the development of DE disease.Methods:A high-sugar and high-fat diet and streptozotocin injection-induced DE rat model was used. β-asarone was administered for four weeks. The experiment used the Morris water maze test, biochemical index detection, and many methods to evaluate the neuroprotective effect of β-asarone on DE rats from various aspects and understand its mechanism.Results:β-asarone reduced neuronal cell damage and significantly improved the learning and memory ability of DE rats. In addition, β-asarone can reduce the oxidative stress response and amyloid-β accumulation in the brain of DE model rats and increase the content of brain-derived neurotrophic factor (BDNF) in the brain tissue, thereby reducing neuronal cell apoptosis and playing a protective role.Conclusion:β-asarone can reduce the accumulation of oxidative stress and amyloid-β in the brain, increase the content of BDNF, reduce the apoptosis of neuronal cells, and exert neuronal protection, thereby improving the learning and memory ability of DE model rats.

Depression and Autoimmune Hypothyroidism-Their Relationship and the Effects of Treating Psychiatric and Thyroid Disorders on Changes in Clinical and Biochemical Parameters Including BDNF and Other Cytokines-A Systematic Review.

Various autoimmune diseases, including autoimmune hypothyroidism (AHT), are associated with a higher risk of developing mood disorders throughout life. Depression is accompanied by the changes in the levels of inflammatory and trophic factors, including interleukins (IL-1beta, IL-2, IL-6), interferon alpha (IFN-alpha), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), and brain derived neurotrophic factor (BDNF). Disclosure of the relationship between the coexistence of depression and AHT indicates that the pathomechanism of depression may be related to the changes in the immune system, it is also possible that both conditions may be caused by the same immune processes. The above hypothesis is indirectly supported by the observations that the treatment with both antidepressants and levothyroxine leads to a decrease in the levels of proinflammatory cytokines with an increase in BDNF concentrations, simultaneously correlating with an improvement in the clinical parameters. However, so far there are no long-term studies determining the causal relationship between depression, thyroid autoantibodies, and cytokine profile, which could bring us closer to understanding the interrelationships between them and facilitate the use of an adequate pharmacotherapy, not necessarily psychiatric. We consider the above issues to be insufficiently investigated but of great importance. This article is an overview of the available literature as well as an introduction to our research project.

Short communication: Serum levels of brain-derived neurotrophic factor and association with pro-inflammatory cytokines in acute and recovered anorexia nervosa

Brain-derived neurotrophic factor (BDNF) is a neuroprotective molecule known to be involved in neuroplasticity, learning and memory. Additionally, it may mitigate the effects of inflammation on the brain. There is inconclusive evidence as to whether reductions in BDNF found in AN are related to features associated with the illness such as changes in inflammatory markers and comorbidities, and whether they persist after recovery. This cross-sectional study measured BDNF and 36 inflammatory markers in the serum of individuals recovered from AN (rec-AN; n = 24), with acute AN (n = 56), and healthy controls (n = 51). We (a) compared BDNF concentrations between AN, rec-AN and controls including four pre-determined covariates; (b) assessed the relationship between BDNF and body mass index, eating disorder (ED) psychopathology and depression; and (c) correlated BDNF with inflammatory markers, stratified by group. The AN group showed reductions in BDNF compared to controls and rec-AN. BDNF was negatively associated with depression and ED psychopathology in the whole sample, but not the AN sample. BDNF was positively correlated with three inflammatory markers in the control group (interleukin (IL)-8, Eotaxin-3, tumor necrosis factor (TNF)-α) and negatively correlated with one (IL-16). The only pro-inflammatory marker associated with BDNF in the AN group was TNF-α, and no pro-inflammatory markers were associated with BDNF in the rec-AN group. These results indicate that BDNF serum concentrations may be a state marker of AN. In people with acute AN, BDNF levels seem to be linked to TNF-α signalling. However, BDNF concentrations do not appear to reflect AN symptom severity.

Interleukin-10 Attenuates Behavioral, Immune and Neurotrophin Changes Induced by Chronic Central Administration of Interleukin-1β in Rats

Background: Activated microglia can trigger pro-inflammatory cytokine releases and neuroinflammation, which may inhibit astrocytes to produce neurotrophins and anti-inflammatory factors. Both eventually lead to neuron apoptosis or death. Furthermore, effective antidepressant or anti-dementia treatments can reduce pro-inflammatory cytokines, while enhance interleukin (IL)-10 production. However, the underline mechanism by which IL-10 modulates glial cell function, hence improves cognitive impairment or depression-like behavior is unknown. This study evaluated whether and how IL-10 attenuated chronic IL-1β administration-induced behavioral changes and the possible involved mechanisms. Methods: Rats received intracerebroventricular injection of IL-1β and/or IL-10 for 14 days. Then animal memory and depression-like behavior, pro-inflammatory cytokines, glial activities, expression of brain-derived neurotrophic factor (BDNF), Trk B, p75, and apoptosis-related genes were studied. Results: Compared to controls, significantly increased latent time and swimming distance in the Morris-water-maze, decreased sucrose consumption, and decreased locomotor and center zone entries in the open-field were found in rats administrated with IL-1β. These changes were associated with the reduction of GFAP expression, and concentrations of BDNF and anti-inflammatory cytokine IL-10, but the increase in the expressions of CD11b, TrkB, p75, and Caspase-3, the ratio of Bax/Bcl-2, and the concentrations of IL-1β, tumor necrosis factor-α, and IL-6. IL-10 treatment markedly attenuated IL-1β-induced above changes, except for the expressions of neurotrophin receptors. Conclusion: IL-10-improved behavioral changes may be through suppressing microglia activity and inflammation, while restoring astrocyte function and BDNF expression.

Symptom cluster profiles following traumatic orthopaedic injuries

BackgroundMillions of Americans experience traumatic orthopaedic injuries (TOIs) annually. Post-injury symptoms of acute stress disorder (ASD), anxiety, depression, pain, and sleep disturbance are common. Symptoms often present in clusters. Symptom cluster profiles phenotypically characterize TOI survivors’ experiences with clustered symptoms. Expression of brain-derived neurotrophic factor (BDNF) may contribute to the biological underpinnings of symptom cluster profile membership. MethodsWe recruited hospitalized TOI survivors within 72 hours of injury. We measured symptoms of ASD with the Acute Stress Disorder Scale and symptoms of anxiety, depression, pain, and sleep disturbance with Patient-Reported Outcomes Measurement Information System (PROMIS) short forms. We measured serum BDNF concentrations with enzyme-linked immunosorbent assay (ELISA) and identified rs6265 genotypes with TaqMan real-time PCR. We performed latent profile analysis to identify the symptom cluster profiles. We identified the variables associated with symptom cluster profile membership with unadjusted and adjusted multinomial logistic regression. ResultsWe identified 4 symptom cluster profiles characterized by symptom severity that we labelled Physical Symptoms Only, and Mild, Moderate, and Severe Psychological Distress. Age, self-identified Black race, resilience, and serum BDNF concentrations were associated with lower odds, and female sex with higher odds, of being in the Psychological Distress clusters. Clinical characteristics and rs6265 genotypes were not associated with symptom cluster profile membership. ConclusionTOI survivors experience distinct symptom cluster profiles. Sociodemographic characteristics and serum BDNF concentrations, not clinical characteristics, were associated with symptom cluster profile membership. These findings support comprehensive symptom screening and treatment for all TOI survivors and further evaluating BDNF as a biomarker of post-injury symptom burden.

The Effects of High Intensive Interval Training (HIIT) on Brain-Derived Neurotrophic Factor (BDNF) and Cardiovascular Health: A Review

High-intensity interval training (HIIT) programs have lately gained popularity because they produce beneficial adaptations for both inactive and athletes, as well as positive health and performance benefits and time efficiency. Therefore, it was purposed to review scientific research results about the effects of HIIT programs on BDNF and cardiovascular health. Although there are research findings suggesting that HIIT may be an effective strategy for promoting elevation of BDNF concentrations, current research seems to be rather limited and inconclusive. It can be thought that exercise intensity is a factor affecting BDNF activation. In healthy people, there seems to be a positive linear relationship between exercise intensity and BDNF levels of acute exercise. However, further experimental studies are needed to elucidate the effect of HIIT on BDNF in humans with metabolic or cardiovascular diseases. However, it can be suggested that high intensity can be an significant achievement factor to design an effective exercise programs and the HIIT methodology has a critical importance for improving cardiovascular function, particularly in healthy individuals. In conclusion, while existing studies show that high-intensity interval training (HIIT) programs can improve cardiovascular health in some populations, further scientific research is needed to determine the efficiency of this strategy in producing physiological adaptation to exercise.

Lactobacillus paracasei CCFM1229 and Lactobacillus rhamnosus CCFM1228 Alleviated Depression- and Anxiety-Related Symptoms of Chronic Stress-Induced Depression in Mice by Regulating Xanthine Oxidase Activity in the Brain.

Depression is a common mood disorder that affects around 350 million people worldwide. We studied the effect of supplementation with Lactobacillus strains for the treatment of depression. Except for control group (n = 8), C57BL/6J mice were treated with Lactobacillus during six weeks of chronic unpredictable stress (depression group: n = 9, Lactobacillus intervention group: n = 7). L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly reduced depressive behaviour in the forced swimming test and tail suspension test, significantly reduced anxiety behaviour in the open field test, and reduced anxiety behaviour in the marble burying test and light/dark box test. L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly increased the brain serotonin and brain-derived neurotrophic factor concentrations, and CCFM1229 significantly decreased the serum corticosterone concentration, all of which are closely associated with the relief of depressive symptoms. Furthermore, CCFM1229 and CCFM1228 were shown to regulate purine metabolism in mice, as indicated by decreases in brain xanthine oxidase activity and an increase in liver adenosine deaminase activity. Anxiety- and depression-related indicators were significantly associated with xanthine oxidase activity in the cerebral cortex. The strains CCFM1229 and CCFM1228 reduced anxiety- and depression-related behaviour in a mouse model of chronic stress-induced depression, which may be achieved by regulating the activity of brain xanthine oxidase.

Clathrin-nanoparticles deliver BDNF to hippocampus and enhance neurogenesis, synaptogenesis and cognition in HIV/neuroAIDS mouse model

Brain derived neurotrophic factor (BDNF) promotes the growth, differentiation, maintenance and survival of neurons. These attributes make BDNF a potentially powerful therapeutic agent. However, its charge, instability in blood, and poor blood brain barrier (BBB) penetrability have impeded its development. Here, we show that engineered clathrin triskelia (CT) conjugated to BDNF (BDNF-CT) and delivered intranasally increased hippocampal BDNF concentrations 400-fold above that achieved previously with intranasal BDNF alone. We also show that BDNF-CT targeted Tropomyosin receptor kinase B (TrkB) and increased TrkB expression and downstream signaling in iTat mouse brains. Mice were induced to conditionally express neurotoxic HIV Transactivator-of-Transcription (Tat) protein that decreases BDNF. Down-regulation of BDNF is correlated with increased severity of HIV/neuroAIDS. BDNF-CT enhanced neurorestorative effects in the hippocampus including newborn cell proliferation and survival, granule cell neurogenesis, synaptogenesis and increased dendritic integrity. BDNF-CT exerted cognitive-enhancing effects by reducing Tat-induced learning and memory deficits. These results show that CT bionanoparticles efficiently deliver BDNF to the brain, making them potentially powerful tools in regenerative medicine.

BDNF and Cortisol in the Diagnosis of Cocaine-Induced Depression.

BackgroundMajor depressive disorder (MDD) and cocaine use disorder (CUD) are related with disability and high mortality rates. The assessment and treatment of psychiatric comorbidity is challenging due to its high prevalence and its clinical severity, mostly due to suicide rates and the presence of medical comorbidities. The aim of this study is to investigate differences in brain derived neurotrophic factor (BDNF) and cortisol plasmatic levels in patients diagnosed with CUD-primary-MDD and CUD-induced-MDD and also to compare them to a sample of MDD patients (without cocaine use), a sample of CUD (without MDD), and a group of healthy controls (HC) after a stress challenge.MethodsA total of 46 subjects were included: MDD (n = 6), CUD (n = 15), CUD-primary-MDD (n = 16), CUD-induced-MDD (n = 9), and 21 HC. Psychiatric comorbidity was assessed with the Spanish version of the Psychiatric Research Interview for Substance and Mental Disorders IV (PRISM-IV), and depression severity was measured with the Hamilton Depression Rating Scale (HDRS). Patients were administered the Trier Social Stress Test (TSST) before and after the biological measures, including BDNF, and cortisol levels were obtained.ResultsAfter the TSST, Cohen's d values between CUD-primary-MDD and CUD-induced-MDD increased in each assessment from 0.19 post-TSST to 2.04 post-90-TSST. Pairwise differences among CUD-induced-MDD and both MDD and HC groups had also a large effect size value in post-30-TSST and post-90-TSST. In the case of the BDNF concentrations, CUD-primary-MDD and CUD-induced-MDD in post-90-TSST (12,627.27 ± 5488.09 vs.17,144.84 ± 6581.06, respectively) had a large effect size (0.77).ConclusionResults suggest a different pathogenesis for CUD-induced-MDD with higher levels of cortisol and BDNF compared with CUD-primary-MDD. Such variations should imply different approaches in treatment.

High maternal BMI and low maternal blood BDNF may determine the limit of detection of amniotic fluid BDNF throughout gestation: Analysis of mother-fetus trios and literature review

ObjectiveAn increasing number of studies show the importance of brain-derived neurotrophic factor (BDNF) acting at the feto-placental interface, however, only a few studies describe BDNF levels in amniotic fluid (AF).MethodsIn this cross-sectional, prospective study, 109 maternal blood-amniotic fluid pairs (including 66 maternal blood-fetal-blood-amniotic fluid trios) were analyzed. BDNF concentrations were measured with a commercially available immunoassay.ResultsIn 71 AF from 109 samples, AF-BDNF concentrations were below the lowest limit of Quantitation (LLoQ) of 1.19 pg/ml (group A), leaving 38 samples with measurable BDNF concentrations (group B). Patients in group A showed significantly higher maternal BMI before pregnancy (mean±SD 26.3± 6.7 (kg/m2) vs. 23.8 ±4.5 (kg/m2) p = 0.04) and lower maternal blood BDNF concentrations than the other group (mean±SD 510.6 ± 554.7 pg/ml vs. mean±SD 910.1± 690.1 pg/ml; p<0.0001). Spearman correlation showed a negative correlation between maternal BMI before pregnancy and maternal BDNF concentrations (r = -0.25, p = 0.01).ConclusionOur study is the first to correlate AF-BDNF samples with the corresponding maternal and fetal blood-BDNF samples. The significant negative correlation between maternal BMI before pregnancy and maternal BDNF and AF-BDNF concentrations below the limit of detection has to be evaluated in further studies.