Increased Brain-derived Neurotrophic Factor Levels Research Articles

Subthalamic nucleus deep brain stimulation does not alter growth factor expression in a rat model of stable dopaminergic deficiency

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) has been a highly effective treatment option for mid-to-late-stage Parkinson’s disease (PD) for decades. Besides direct effects on brain networks, neuroprotective effects of STN-DBS – potentially via alterations of growth factor expression levels – have been proposed as additional mechanisms of action. ObjectiveIn the context of clarifying DBS mechanisms, we analyzed brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) levels in the basal ganglia, motor and parietal cortices, and dentate gyrus in an animal model of stable, severe dopaminergic deficiency. MethodsWe applied one week of continuous unilateral STN-DBS in a group of stable 6-hydroxydopamine (6-OHDA) hemiparkinsonian rats (6-OHDASTIM) in comparison to a 6-OHDA control group (6-OHDASHAM) as well as healthy controls (CTRLSTIM and CTRLSHAM). BDNF and GDNF levels were determined via ELISAs. ResultsThe 6-OHDA lesion did not result in a persistent alteration in either BDNF or GDNF levels in a model of severe dopaminergic deficiency after completion of the dopaminergic degeneration. STN-DBS modestly increased BDNF levels in the entopeduncular nucleus, but even impaired BDNF and GDNF expression in cortical areas. ConclusionsSTN-DBS does not increase growth factor expression when applied to a model of completed, severe dopaminergic deficiency in contrast to other studies in models of modest and ongoing dopaminergic degeneration. In healthy controls, STN-DBS does not influence BDNF or GDNF expression. We consider these findings relevant for clinical purposes since DBS in PD is usually applied late in the course of the disease.

Physical activity in a swimming pool attenuates memory impairment by reducing glutamate and inflammatory cytokines and increasing BDNF in the brain of mice with type 2 diabetes

Type 2 diabetes is a risk factor for the development of cognitive impairment. Increasing evidence suggests that regular exercise is beneficial for the treatment of clinical symptoms in diabetic patients. The current study aimed to evaluate whether increasing physical activity through swimming training can reduce memory impairment in an animal model of type 2 diabetes. Diabetes and non-diabetes mice underwent swimming training for four weeks, and then working, spatial, and recognition memory were evaluated using three behavioral tests. Body weight, glucose, and insulin resistance were monitored. We also measured inflammatory cytokines (interleukin (IL)− 6, IL-1β, and tumor-necrosis-factor (TNF)-α), an anti-inflammatory cytokine (IL-10), and brain-derived-neurotrophic-factor (BDNF), and glutamate levels in the hippocampus or prefrontal cortex of mice. The findings showed that diabetes increased body weight, glucose, and insulin resistance, impaired working, spatial and recognition memory, increased levels of IL-6, IL-1β, TNF-α, and glutamate levels, and decreased BDNF in the hippocampus of diabetic mice. While higher physical activity was associated with reduced body weight, glucose, and insulin resistance, attenuated memory impairment, IL-6, IL-1β, TNF-α, and glutamate, and increased BDNF levels in the hippocampus and prefrontal cortex of diabetic mice. This study shows that swimming training can normalize body weight and glucose-insulin axis and reduce inflammation and glutamate in the hippocampus and enhance the neurotrophic system in both the hippocampus and prefrontal cortex of diabetic mice. This study also suggests that higher physical activity through swimming training can improve cognitive impairment in a mouse model of type 2 diabetes.

The effect of omega 3 supplementation on serum brain-derived neurotrophic factor: A systematic review and meta-analysis

The brain-derived neurotrophic factor (BDNF) is crucial for the metabolic and mental health of an individual. Numerous intervention experiments with the goal of increasing BDNF levels have been conducted as a result of the fact that higher concentrations are linked to better cognitive function. In order to obtain a better viewpoint from them, this study was conducted as the first study in this field, with the aim of comprehensively investigating the effects of omega-3 supplementation on BDNF. Scopus, PubMed/Medline, Web of Science, and Embase databases or platform were searched using standard keywords to identify all controlled trials investigating the BDNF effects of omega 3 supplementation. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes. We used the Egger's test to determine whether there was publication bias. Eleven studies with 698 participants’ were included in this study. Results of random-effects meta-analysis indicated that BDNF levels were significantly increased after supplementation with omega 3 compared with the control group (pooled WMD of 1.01 μmol/L; 95% confidence interval [CI] 0.35 to 1.67; P =0.003; I2 = 97.7%) and this increase was even greater with intervention duration >10 weeks and doses ≤1500 mg/day. In addition, the effect of omega-3 supplementation on increasing glucose levels was greater in people under 50 years of age and patients with psychological diseases. In general, the present systematic review and meta‐regression analysis demonstrated that omega 3 supplementation may be able to significantly improve BDNF.

Changes in TRPV1 Receptor, CGRP, and BDNF Expression in Rat Dorsal Root Ganglion with Resiniferatoxin-Induced Neuropathic Pain: Modulation by Pulsed Radiofrequency Applied to the Sciatic Nerve.

Pulsed radiofrequency (PRF) is a safe method of treating neuropathic pain by generating intermittent electric fields at the needle tip. Resiniferatoxin (RTX) is an ultrapotent agonist of transient receptor potential vanilloid subtype-1 (TRPV1) receptors. We investigated the mechanism of PRF using a rat model of RTX-induced neuropathic pain. After administering RTX intraperitoneally, PRF was applied to the right sciatic nerve. We observed the changes in TRPV1, calcitonin gene-related peptide (CGRP), and brain-derived neurotrophic factor (BDNF) in the dorsal root ganglia by western blotting. Expressions of TRPV1 and CGRP were significantly lower in the contralateral (RTX-treated, PRF-untreated) tissue than in control rats (p<0.0001 and p<0.0001, respectively) and the ipsilateral tissues (p<0.0001 and p<0.0001, respectively). BDNF levels were significantly higher in the contralateral tissues than in the control rats (p<0.0001) and the ipsilateral tissues (p<0.0001). These results suggest that, while TRPV1 and CGRP are decreased by RTX-induced neuronal damage, increased BDNF levels result in pain development. PRF may promote recovery from neuronal damage with concomitant restoration of TRPV1 and CGRP, and exert its analgesic effect by reversing BDNF increase. Further research is required to understand the role of TRPV1 and CGRP restoration in improving mechanical allodynia.

High-intensity interval training ameliorates chronic unpredictable mild stress-induced depressive behaviors via HDAC2-BDNF signaling in the ventral hippocampus

Major depressive disorder (MDD) is a devastating psychiatric disease, and current therapies could not well meet the demand for MDD treatment. Exercise benefits mental illness, and notably, exercise has been recommended as an alternative option for MDD treatment in some countries. However, the paradigm and intensity of exercise for MDD treatment has yet to be determined. High-intensity interval training (HIIT) is a potent and time-efficient type of exercise training and has gained popularity in recent years. In this study, we exposed the mice to chronic unpredictable mild stress (CUMS) and found HIIT exerted substantial antidepressant effect. Moreover, HIIT further enhanced the antidepressant effect of fluoxetine, a classic antidepressant in the clinic, confirming the antidepressant role of HIIT. HIIT significantly reversed the CUMS-induced upregulations in HDAC2 mRNA and protein level in the ventral hippocampus. We also found HIIT rescued the CUMS-induced downregulation in the expression of brain-derived neurotrophic factor (BDNF) and HDAC2 overexpression counteracted the HIIT-induced increase in BDNF level. More importantly, both virus-mediated HDAC2 overexpression and microinfusion of TrkB-Fc, a BDNF scavenger, in the ventral hippocampus abolished the antidepressant effect of HIIT. Together, our results strongly demonstrate that HIIT attenuates depressive behaviors, probably via HDAC2-BDNF signaling pathway and reveal that HIIT may serve as an alternative option for MDD treatment.

Increased levels of brain-derived neurotrophic factor in cultures of nervous cells treated with a selective serotonin reuptake inhibitor

Introduction. The effects of antidepressants such as fluoxetine on brain plasticity are associated with increased transcription and signaling of trophic factors such as brain-derived neurotrophic factor (BDNF), which enhances synaptic and neurogenic processes. Objective. To evaluate whether treatment with fluoxetine could increase BDNF levels in retinal cells. Method. To conduct the experiment, retinas were dissected from neonatal rats and cultured in complete culture medium. Next, the cultures designated for the experimental group were treated with 1µM of fluoxetine and maintained for 2, 12, 24, 48, or 72 hours in vitro. The cultures designated for the control group underwent the same protocol, but did not receive the fluoxetine treatment. The levels of BDNF were determined by Western blot analysis, and the data were analyzed by Student's t-test to compare the two groups (control and experimental). Results. The results showed that cultures treated with fluoxetine for 12, 24, and 48 hours had significantly higher levels of BDNF than the control group. Conclusion. The findings suggest that treatment with fluoxetine may have potential therapeutic effects on retinal cells by increasing BDNF levels. This adds to the existing evidence on the role of BDNF in mediating the therapeutic effects of antidepressants and highlights the potential for further research on the use of antidepressants in the treatment of retinal diseases.

BDNF changes as a result of non-pharmacological interventions in schizophrenia – A scoping review

Schizophrenia is a severe, chronic, neuropsychiatric disorder, with a complex, yet to be elucidated aetiology. The altered connectivity responsible for the wide range of symptoms in schizophrenia, stemming from genetic, metabolic, as well as environmental factors, has had researchers focusing on the identification of more and more “players” carrying certain specificity for the disease. One of these factors is the brain-derived neurotrophic factor (BDNF) - the most abundant growth factor in the central nervous system (CNS) and most frequently researched. Here, we set to explore the evidence pertaining to a correlational change in serum BDNF levels while individuals with schizophrenia undergo a non-pharmacological/psychotherapeutic intervention. We performed a systematic search of studies evaluating BDNF changes as a result of psychotherapeutic interventions in schizophrenia, in four databases: APA PsycInfo, Pubmed, Medline and EBSCO. The keywords “schizophrenia”, “psychotherapy OR psychosocial”, and “BDNF OR brain-derived neurotrophic factor” were searched for on all databases. The search yielded 46 titles and abstracts, of which 10 met the criteria for inclusion. The interventions consisted in neurofeedback, auditory training, cognitive remediation and lifestyle changes and behaviour therapy, as well as exercise. Serum BDNF levels were assessed systematically, showing significant increases as a result of the interventions in all studies, except three, where other changes are discussed. The studies discussed in this review support, overall, the idea of an increase in BDNF levels, as well as cognitive and clinical improvements secondary to non-pharmacological interventions. Several limitations and future directions are discussed.

Red foxtail millet upregulates brain-derived neurotrophic factor levels in vitro and in vivo.

Upregulation of the brain-derived neurotrophic factor (BDNF) in the brain can help in the prevention and treatment of depression. BDNF is synthesized in various peripheral tissues, as well as in the brain, and can reach the brain via the blood-brain barrier. Therefore, foods that upregulate peripheral BDNF levels may aid in depression management. We previously showed the BDNF-upregulating effect of white foxtail millet (WFM) using the human renal adenocarcinoma ACHN cell line, capable of producing and secreting BDNF. However, whether other varieties of foxtail millet can also upregulate BDNF is unclear. Herein, we examined the effects of red foxtail millet (RFM) on BDNF production in vitro and in vivo. RFM methanol extracts significantly increased BDNF levels in the culture medium of ACHN cells, and the levels were higher than those with WFMtreatment. Serum BDNF concentrations in rats fed a standard diet containing 20% RFM for 5 weeks were significantly higher than those in the control. Furthermore, the butanol fraction of the RFM methanol extract significantly increased BDNF levels in the culture medium of ACHN cells and upregulated BDNF mRNA expression in ACHN cells. Our results suggest that RFM has potential as a food material with BDNF-inducing activity.

Can exercise prevent the age‐related decline in adaptive homeostasis? Evidence across organisms and tissues

Can exercise prevent the age‐related decline in adaptive homeostasis? Evidence across organisms and tissues

Brain-derived neurotrophic factor and matrix metalloproteinase-9 activity during rehabilitation therapy of schizophrenic patients - environmental pilot study.

The aim of the study was to evaluate the peripheral level of brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) during rehabilitation therapy, combined with neurofeedback in schizophrenic patients, and to investigate whether these biomarkers are related to psychopathological symptoms, changes in auditory evoked potentials (AEPs), and quantitative EEG (QEEGs) mapping. The study involved two groups of patients diagnosed with paranoid schizophrenia in partial remission who participated in a 3-month structured rehabilitation programme combined with neurofeedback (REH group) and a standard support group (CON group). The following parameters were assessed: BDNF and MMP-9 serum levels, AEPs, QEEGs, and psychopathological symptoms (PANSS). A clinical improvement within the 3-month rehabilitation therapy course was correlated with the increase in BDNF and MMP-9 serum level. Despite the increase in BDNF and MMP-9 during the 3-month rehabilitation therapy, it was not possible to demonstrate any strong and significant correlation between the 2 examined neuropeptides. During the 3-month rehabilitation therapy, the theta waveform share reduction in QEEG, P50 latency reduction and amplitude increase correlated with PANSS Total and MMP-9 results. All clinical (PANSS Positive, Negative, General, Total) and biochemical results (BDNF, MMP-9) of the REH group changed significantly over the 3-month period. Positive symptoms improved only in the CON group.

Ca2+-Permeable TRPV1 Receptor Mediates Neuroprotective Effects in a Mouse Model of Alzheimer's Disease via BDNF/CREB Signaling Pathway.

Transient receptor potential vanilloid 1 (TRPV1) protein is a Ca2+-permeable non-selective cation channel known for its pain modulation pathway. In a previous study, it was discovered that a triple-transgenic Alzheimer's disease (AD) mouse model (3xTg-AD+/+) has anti-AD effects. The expression of proteins in the brain-derived neurotrophic factor (BDNF)/cAMP response element binding protein (CREB) pathway in a 3xTg-AD/TRPV1 transgenic mice model was investigated to better understand the AD regulatory effect of TRPV1 deficiency. The results show that TRPV1 deficiency leads to CREB activation by increasing BDNF levels and promoting phosphorylation of tyrosine receptor kinase B (TrkB), extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and CREB in the hippocampus. Additionally, TRPV1 deficiency-induced CREB activation increases the antiapoptotic factor B-cell lymphoma 2 (Bcl-2) gene, which consequently downregulates Bcl-2-associated X (Bax) expression and decreases cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP), which leads to the prevention of hippocampal apoptosis. In conclusion, TRPV1 deficiency exhibits neuroprotective effects by preventing apoptosis through the BDNF/CREB signal transduction pathway in the hippocampus of 3xTg-AD mice.

Serum short chain fatty acids mediate hippocampal BDNF and correlate with decreasing neuroinflammation following high pectin fiber diet in mice.

Dietary components, such as prebiotic fiber, are known to impact brain chemistry via the gut-brain axis. In particular, short chain fatty acids (SCFAs) generated from excessive soluble fiber consumption are thought to impact neuroimmune signaling and brain function through increased production of neurotropic factors. Given reports that high dietary fiber intake is associated with increased mental health and improved quality of life scores, we set out to identify whether changes in SCFA levels as a result of a high soluble fiber diet mediate hippocampal neuroinflammation and brain derived neurotrophic factor (BDNF) in mice. Adult male and female C57BL/6 mice were fed a 1-month high pectin fiber or cellulose-based control diet. Following 1 month of excessive pectin consumption, serum SCFAs were measured using gas chromatography-mass spectrometry (GC-MS) and hippocampal cytokines and BDNF were assessed via multiplex magnetic bead immunoassay. Pectin-based fiber diet increased circulating acetic acid in both sexes, with no effect on propionic or butyric acid. In the hippocampus, a high fiber diet decreased TNFa, IL-1ß, IL-6, and IFNγ and increased BDNF levels. Furthermore, increased SCFA levels were inversely correlated with neuroinflammation in the hippocampus, with acetic acid revealed as a strong mediator of increased BDNF production. Collectively, these findings highlight the beneficial effects of fiber-induced molecular changes in a brain region known to influence mood- and cognition-related behaviors. Dietary composition should be considered when developing mental health management plans for men and women with an emphasis on increasing soluble fiber intake.

Transcranial direct current stimulation alleviated ischemic stroke induced injury involving the BDNF-TrkB signaling axis in rats

Ischemic stroke causes a complicated sequence of apoptotic cascades leading to neuronal damage and functional impairments. Transcranial direct current stimulation (tDCS) is a non-invasive treatment technique that uses electrodes to deliver weak current to the head. It could influence brain activity and has a crucial role in neuronal survival and plasticity. The current study investigated the neuroprotective effects and potential mechanisms of tDCS by brain-derived neurotrophic factor (BDNF) and its related receptor tropomyosin-receptor kinase B (TrkB) against apoptosis following ischemic injury in vivo.The effect of consecutive treatment with tDCS for seven days on rats after Middle cerebral artery occlusion/reperfusion (MCAO/R) surgery was studied. Western blotting, immunofluorescent staining, TUNEL assay, and electron microscope were conducted seven days after tDCS treatment, and the motor function was assessed at 1, 3, and 7 days. Activities of BDNF-TrkB signaling axis and apoptosis-related proteins were determined in the cerebral cortex. At seven days after tDCS treatment, it increased BDNF levels and promoted the regeneration of axons compared with the MCAO/R group. There was also a reduction in neuronal apoptosis and improved functional deficits. Whereafter, a TrkB receptor inhibitor K252a was administrated to clarify whether the neuroprotection of tDCS is exerted via BDNF-TrkB signaling. The results depicted that K252a application significantly inhibited the neuroprotection impact of tDCS treatment. It was accompanied by a significant downregulation of phosphorylation of TrkB, PI3K, and Akt.Our study investigated the neuroprotective effects of tDCS against ischemic injury. The results indicate that upregulation of BDNF and its critical receptor TrkB, as well as its downstream PI3K/Akt pathway, were involved in the protective effects exerted by tDCS.

Influence of altered serum and muscle concentrations of BDNF on electrophysiological properties of spinal motoneurons in wild-type and BDNF-knockout rats

The purpose of this study was to determine whether altered serum and/or muscle concentrations of brain-derived neurotrophic factor (BDNF) can modify the electrophysiological properties of spinal motoneurons (MNs). This study was conducted in wild-type and Bdnf heterozygous knockout rats (HET, SD-BDNF). Rats were divided into four groups: control, knockout, control trained, and knockout trained. The latter two groups underwent moderate-intensity endurance training to increase BDNF levels in serum and/or hindlimb muscles. BDNF and other neurotrophic factors (NFs), including glial cell-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), nerve growth factor (NGF), and neurotrophin-4 (NT-4) were assessed in serum and three hindlimb muscles: the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (Sol). The concentrations of tropomyosin kinase receptor B (Trk-B), interleukin-15 (IL-15), and myoglobin (MYO/MB) were also evaluated in these muscles. The electrophysiological properties of lumbar MNs were studied in vivo using whole-cell current-clamp recordings. Bdnf knockout rats had reduced levels of all studied NFs in serum but not in hindlimb muscles. Interestingly, decreased serum NF levels did not influence the electrophysiological properties of spinal MNs. Additionally, endurance training did not change the serum concentrations of any of the NFs tested but significantly increased BDNF and GDNF levels in the TA and MG muscles in both trained groups. Furthermore, the excitability of fast MNs was reduced in both groups of trained rats. Thus, changes in muscle (but not serum) concentrations of BDNF and GDNF may be critical factors that modify the excitability of spinal MNs after intense physical activity.

Effect of psychotherapy on peripheral BDNF concentration levels in patients with bipolar disorder. A systematic review

Introduction Psychotherapy is a treatment of proven efficacy in bipolar disorder (BD), but little is known about the molecular and cellular mechanisms that it produces in the brain. Brain-derived neurotrophic factor (BDNF) is thought to be important in neuroplasticity and could be increased by psychopharmaceuticals and psychotherapy in BD patients, but evidence in the literature is limited.ObjectivesTo analyze the scientific studies that relate psychotherapies with the increase in BNDF levels in patients with BD.MethodsSystematic review with PRISMA recommendations in PUBMED and Web of Science in July 2022. The search was performed using the combination of keywords “bipolar disorder” AND (“BDNF” OR “Brain Derived Neurotrophic Factor”) AND “psychotherapy”.ResultsWith the initial search, 839 studies were obtained, finally 8 articles were analyzed. The available literature supports the role of psychotherapy in increasing BNDF in patients with BD.ConclusionsBDNF could be a biomarker of therapeutic efficacy in BD. Psychotherapy increases BDNF levels. No differences were found between the different types of psychotherapies. More studies are needed to determine the mechanisms by which psychotherapies produce molecular changes in the brain.Disclosure of InterestNone Declared

Action mechanisms of Oviductus ranae on perimenopausal depression model mice via regulation of phosphoinositol 3 kinase/AKT signalling

Oviductus ranae (OR) is an animal-based traditional Chinese medicine. In this work, its underlying mechanism of action in mice model of perimenopausal depression (PMD) was investigated. Network pharmacology and molecule docking analysis were conducted to identify potential targets and chemical components of OR in PMD. Subsequently, 60 female mice were ovariectomized and subjected to chronic unpredictable mild stress to establish the PMD model. After 14 days of OR administration on PMD mice, the depression-like behavioral were evaluated using sucrose preference, forced swimming, tail suspension, open field and morris water maze tests. Hippocampal tissues were collected to observe pathological changes via haematoxylin-eosin (H&amp;E) staining, and immunohistochemical analysis was performed to detect the expression of the protein kinase B (AKT), phosphoinositol 3 kinase (PI3K), and oestrogen receptor β (ERβ). Western blot (WB) analysis was Conducted to detect the expression of PI3K/AKT signalling pathway. In the results, 18 potential targets and two chemical components of OR in PMD were identified. KEGG suggested that the PI3K/AKT signaling pathway was frequently involved in treatment of PMD with OR. Molecular docking showed that β-sitosterol in OR had the best docking effect with the target. OR treatment improved depression-like behaviour of PMD mice, significantly improved pPI3K/PI3K, pAKT/AKT, and pCREB/CREB ratios and brain derived neurotrophic factor. These findings suggested that OR may alleviate PMD and increase brain-derived neurotrophic factor levels, and has a certain therapeutic effect on PMD by up-regulating the expression of ERβ and activating the PI3K/AKT pathway. Overall, our study highlights OR as a promising therapeutic candidate for PMD.

Brain-Derived Neurotrophic Factor (BDNF) as an Indicator for Effects of Cognitive Behavioral Therapy (CBT): A Systematic Review.

Brain-derived neurotrophic factor (BDNF) is a protein affecting survival of existing neurons and neuronal maturation. Patients suffering from several mental disorders exhibit reduced BDNF levels comparing to healthy population. In this systematic review we aim to evaluate the effect of broadly defined cognitive behavioral therapy (CBT) on BDNF levels in psychiatric patients. A literature search was performed using PubMed and Google Scholar data bases. The resources were searched between 14 January and 3 February 2022. Following the inclusion criteria, a total of 10 randomized-controlled trials were included. The results of our research indicate that BDNF levels might be considered an indicator of a result achieved in psychotherapy of cognitive functions. However, no such correlation was observed for mindfulness-based practices intended to lower stress levels or improve the quality of life. It is important to notice that present research showed no consistent correlation between the increase in BDNF levels and the perceived effectiveness of the procedures. Thus, the exact role of BDNF remains unknown, and so far, it cannot be taken as an objective measure of the quality of the interventions.

BDNF as a potential predictive biomarker for patients with pediatric cerebral palsy

Background: Cerebral palsy (CP) is the most common motor disability in children, which is instigated by damage to the developing brain that affects the ability to control the muscles. The main types of CP are spastic CP, dyskinesia CP and mixed CP. The aim of this work was to estimate the concentrations of complete blood count (CBC), erythrocytic sedimentation rate (ESR), C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF), and tumor necrosis factor-α (TNF-α) in children with CP compared to the control group. Methods: A total of 75 Egyptian children were enrolled in this study, 45 had CP and 30 were controls. CBC, ESR, CRP, BDNF, and TNF-α were assessed. Results: The ESR, CRP and TNF-α levels showed statistically significant increases in cases compared with controls. While the neutrophil/lymphocyte ratio and the BDNF levels were significantly lower in CP compared with the controls. When comparing the different groups of CP with each other; there were no significant differences. Regarding the correlation of BDNF and different studied parameters, our study showed a positive correlation between BDNF and TNF levels only within the group with spastic CP. Conclusions: BDNF may be considered as a biomarker or treatment target for CP to avoid further complications as still there is insufficient progress in the prediction, early diagnosis, treatment, and prevention of CP. Furthermore, searching for novel strategies to increase BDNF levels may open a new opportunity for the treatment of CP.

BDNF is a prognostic biomarker involved in immune infiltration of lung adenocarcinoma and is associated with brain metastasis.

Non-small cell lung cancer (NSCLC) is one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies, particularly lung adenocarcinoma (LUAD). Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has been linked to several human malignancies and has been shown to promote LUAD tumorigenesis. However, its function in the tumour immune microenvironment (TIME) remains largely unexplored, especially in complex brain tissue environments. In this study, BDNF was found to be particularly increased in patients with advanced tumour stage, lymphatic metastasis, and distant metastasis, indicating a correlation with LUAD progression. We characterized the prognostic value of BDNF and defined BDNF as an unfavourable prognostic indicator through a common driver gene-independent mechanism in LUAD. Furthermore, patients with increased BDNF levels in primary LUAD might have a higher risk of developing brain metastasis (BM), and central nervous system (CNS) metastasis showed an elevated expression of BDNF compared to their matched primary lesions. Additionally, we investigated the interaction between BDNF and infiltrating immune cells in both primary lesions and paired BM using multiplex immunostaining. The results showed that BDNF might drive an immunosuppressive tumour microenvironment (TME) by re-education of tumour-associated macrophages (TAMs) toward a pro-tumorigenic M2 phenotype, particularly in BM. Our findings demonstrate that BDNF serves as an independent potential prognostic marker and correlates with BM in LUAD. As it is closely related to TAM polarization, BDNF may be a promising immune-related biomarker and molecular target in patients with LUAD.

Effect of vitamin D on serum BDNF level in patients with hypothyroidism caused by autoimmune thyroiditis

Background. Hashimoto’s thyroiditis is a chronic autoimmune disease of the thyroid gland caused by an increase in thyroid antibodies. A growing body of research suggests that patients with Hashimoto’s thyroiditis may suffer from cognitive impairment. Therefore, it is important to identify risk factors that contribute to the development of cognitive impairment in patients with autoimmune thyroiditis to diagnose them early and treat. Given that the influence of thyroid hormones on the brain is undeniable, and their deficiency leads to a variety of neurological complications, early diagnosis and treatment of neurological disorders in thyroid diseases is crucial for preventing further progression of these complications. The purpose of the study is to determine the effect of vitamin D on the level of brain-derived neurotrophic factor (BDNF) in blood serum of patients with hypothyroidism caused by autoimmune thyroiditis. Materials and methods. Twenty-eight patients with hypothyroidism caused by autoimmune thyroiditis were included in the study. The serum level of BDNF was quantified using a solid-phase enzyme-linked immunosorbent assay with a highly sensitive Human BDNF ELISA Kit (Elabscience®, United States, Catalog No E-EL-H0010) on E.I.A. Reader Sirio S (Seac, Italy). Results. In our study, the administration of vitamin D and L-thyroxine led to a 7.4-fold increase in BDNF levels (p&lt;0.001). In the group of patients who took only L-thyroxine, serum content of BDNF increased by 2.1 times. In patients who took cholecalciferol and L-thyroxine, the level of BDNF was 2.48 times higher compared to those who took only L-thyroxine (p&lt;0.001). Conclusions. A positive effect of vitamin D on the serum level of BDNF was found in patients with hypothyroidism caused by autoimmune thyroiditis. Treatment of these individuals using additional administration of cholecalciferol on the background of L-thyroxine proved to be more effective compared to the administration of L-thyroxine alone (p&lt;0.001).