Brain-derived Neurotrophic Factor Levels Research Articles

Differences in Plasma BDNF Levels Between Chronic Primary Musculoskeletal Pain, Fibromyalgia Syndrome, and Asymptomatic Subjects: A Cross-Sectional Study.

This cross-sectional study compared plasma brain-derived neurotrophic factor (BDNF) levels among chronic primary musculoskeletal pain patients, chronic widespread pain patients, and asymptomatic controls. The study included 126 participants aged 18-65, divided into three groups of 42 each. Pain intensity was assessed using a Numeric Rating Scale (NRS), and plasma BDNF levels were measured via ELISA. Differences between groups were evaluated using ANOVA with 2000 bootstrap resamples and a bias-corrected and accelerated method. Results showed significantly higher plasma BDNF levels in chronic widespread pain patients (mean difference [MD] = 0.44; 95% CI = 0.28, 0.62; p < .001) compared to controls, and higher than in chronic primary musculoskeletal pain patients (MD = 0.83; 95% CI = 0.64, 1.02; p < .001). Chronic primary musculoskeletal pain patients had lower plasma BDNF levels compared to controls (MD = -0.39; 95% CI = -0.54, -0.24; p < .001). No significant correlations were observed between plasma BDNF levels and clinical variables. These findings suggest the potential of BDNF as a biomarker to differentiate chronic primary pain conditions.

BDNF and GSK-3beta expression changes underlie the beneficial effects of crocin on behavioral alterations in a rat model of autism induced by prenatal valproic acid administration.

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder characterized by impairments in social interaction, language, and communication and induction of stereotypic behavior. In rodents, prenatal administration of valproic acid (often on 12.5 gestational days) is used for the induction of an ASD-like model. In the present study, we aimed to assess the potential therapeutic effects of crocin (a major component of Saffron, a neuroprotective and anti-inflammatory agent) on behavioral dysfunctions with respect to the level of brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase-3 beta (GSK-3beta) in the medial prefrontal cortex. Valproic acid was intraperitoneally injected at the dose of 600 mg/kg on 12.5 gestational days. BDNF and GSK-3beta expression levels were also measured using real-time PCR. Locomotion, anxiety-like behavior, grooming, and sniffing were also measured in the open-field test. The results showed that prenatal valproic acid administration induced hyperactivity, anxiety-like behavior, increased grooming and sniffing (stereotyped behavior), decreased BDNF levels, and increased GSK-3beta levels in the medial prefrontal cortex. However, crocin dose-dependently restored the effects of prenatal valproic acid administration on behavioral functions and gene expressions. In conclusion, we suggested that BDNF and GSK-3beta expression changes in the medial prefrontal cortex may underlie the pathophysiology of ASD. The therapeutic effects of crocin may be also related to counteracting BDNF and GSK-3beta expression changes induced by prenatal valproic acid.

Relationship between BDNF content in cord blood and early neurobehavior in newborns with subclinical hypothyroidism during pregnancy: a preliminary study

ObjectivesResearch on neurobehavioral abnormalities in neonates of mothers with subclinical hypothyroidism (SCH) is limited. The link between umbilical cord blood brain-derived neurotrophic factor (BDNF) levels and neurobehavioral outcomes in neonates has not been explored. This study investigates the correlation between alterations in umbilical cord blood BDNF levels and early neurobehavioral abnormalities in neonates born to pregnant women with SCH.MethodsThis study recruited 72 pregnant women with SCH and 76 healthy controls (HC). The study collected general information for all subjects, including body mass index, parity, thyroid function assessed during early to late pregnancy, and neonatal birth weight. Neonatal behavioral and neural abilities were evaluated using the Neonatal Behavioral Neurological Assessment (NBNA). BDNF levels in umbilical cord blood were measured using the Enzyme-Linked Immunosorbent Assay method.ResultsThe results indicated that neonates with SCH during pregnancy had lower total NBNA scores, behavioral ability, passive muscle tone, active muscle tone, primitive reflexes, general assessment, and lower levels of cord blood BDNF compared to healthy controls. The cord blood BDNF of newborns with SCH during pregnancy was positively correlated with total NBNA score, behavioral ability, active muscle tone, and general assessment. Moreover, multiple linear regression analysis demonstrated an association between cord blood BDNF levels in pregnant patients with SCH and multiple measures of newborn health, including total NBNA score, behavioral ability, active muscle tone, and general assessment.ConclusionInfants born to pregnant women with SCH exhibit reduced behavioral and neural abilities linked to BDNF levels in umbilical cord blood.

Neurotrophomodulatory effect of TNF-α through NF-κB in rat cortical astrocytes.

Tumor necrosis factor alpha (TNF-α) is a well-known pro-inflammatory cytokine originally recognized for its ability to induce apoptosis and cell death. However, recent research has revealed that TNF-α also plays a crucial role as a mediator of cell survival, influencing a wide range of cellular functions. The signaling of TNF-α is mediated through two distinct receptors, TNFR1 and TNFR2, which trigger various intracellular pathways, including NF-κB, JNK, and caspase signaling cascades. Both TNFR1 and TNFR2 are expressed in astrocytes, which are specialized glial cells essential for maintaining the structural and functional integrity of the central nervous system (CNS). Astrocytes support neuronal function by regulating brain homeostasis, maintaining synaptic function, and supplying metabolic substrates. In addition, astrocytes are known to secrete a variety of growth factors and neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4/5. These neurotrophins play a critical role in supporting neuronal survival, synaptic plasticity, and myelination within the brain. The present study focuses on the role of TNF-α in modulating neurotrophin expression and secretion in rat cortical astrocytes. We demonstrate that TNF-α induces the upregulation of neurotrophins, particularly NGF and BDNF, in cultured astrocytes. This effect is accompanied by an increase in the expression of their respective receptors (TrkA & TrkB), further suggesting a functional modulation of neurotrophic signaling pathways. Notably, we show that the modulation of neurotrophin expression by TNF-α is mediated via the NF-κB signaling pathway. Additionally, we observed that TNF-α also regulates the secretion levels of NGF and BDNF into the culture media of astrocytes in a dose-dependent manner, indicating that TNF-α can modulate both the production and release of these growth factors. Taken together, our findings highlight a previously underexplored neuroprotective role of TNF-α in astrocytes. Specifically, we propose that TNF-α, through the upregulation of neurotrophins, may contribute to maintaining neuronal health and supporting neuroprotection under disease conditions.

Long-term effects of antipsychotics on serum BDNF levels in patients with schizophrenia.

Brain-derived neurotrophic factor (BDNF) is implicated in the etiology of schizophrenia, and peripheral BDNF levels are affected by the short-term antipsychotic treatment. However, the data on their long-term effects on BDNF levels are scarce, and there is no information whether BDNF levels change during sustained remission in relation to values in healthy individuals. The aim of the present study was to compare serum BDNF levels in patients in long-term remission and healthy controls. This study is an extension of our previous research on the effects of olanzapine and risperidone on serum BDNF in acute-episode patients with schizophrenia. Patients who remained in remission for at least 3 years on the same antipsychotic regimen (40 % of the initial cohort) were included. Symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured by ELISA in patients in remission (N = 20), evaluated at baseline, after 6 weeks of treatment and after 3 years of treatment, and in healthy individuals (N = 40). At baseline (p = 0.046) and after 6 weeks of treatment (p = 0.028), patients had significantly lower BDNF levels than controls. However, after 3 years of continuous antipsychotic maintenance treatment, serum BDNF levels were increased compared to baseline and values after 6 weeks of treatment in remitted patients, and were also significantly higher in patients than in healthy controls (p = 0.002). Antipsychotic medications appear to have distinct effects on serum BDNF levels in short-and long-term treatment. It remains to be determined if such finding may be related to potential neuroprotective effects of antipsychotic maintenance treatment.

Effects of pain in lumbosacral stenosis and lifestyle-related factors on brain-derived neurotrophic factor expression profiles.

This study investigated the role of brain-derived neurotrophic factor (BDNF) in patients with degenerative lumbar stenosis, focusing on its expression and correlation with pain intensity. The study examined 96 patients with lumbar stenosis and 85 control participants. BDNF levels in the yellow ligamentum flavum were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and western blot analysis. The results showed significantly higher BDNF expression at both messenger ribonucleic acid (mRNA; fold change = +1.35 ± 0.23; p < 0.05) and protein levels in patients (28.98 ± 6.40 pg/mg) compared to controls (4.56 ± 1.98 pg/mg; p < 0.05). Furthermore, BDNF levels correlated positively with pain intensity reported by patients, with higher expression observed in those experiencing more severe pain. The study also explored the influence of lifestyle factors, such as smoking and alcohol consumption, and related diseases, such as diabetes, on BDNF expression. Smoking, alcohol use, and diabetes were associated with significantly elevated BDNF levels (p < 0.05). These findings suggest that BDNF could serve as a biomarker for pain severity in degenerative lumbar stenosis at the protein level, although this was not consistently observed at the mRNA level; this highlights the potential for BDNF-targeted therapies in managing pain. Future research should involve larger longitudinal studies to validate these findings and explore therapeutic interventions. This study underscores the importance of considering molecular and lifestyle factors in the treatment of degenerative lumbar stenosis, aiming to improve patient outcomes through comprehensive, targeted approaches.

Brain-Derived Neurotrophic Factor (BDNF) as a Potential Biomarker in Brain Glioma: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluates peripheral and CNS BDNF levels in glioma patients. Following PRISMA guidelines, we systematically searched databases for studies measuring BDNF in glioma patients and controls. After screening and data extraction, we conducted quality assessment, meta-analysis, and meta-regression. Eight studies were included. Meta-analysis showed significantly reduced plasma BDNF levels in glioma patients versus controls (SMD: -1.0026; 95% CI: [-1.5284, -0.4769], p = 0.0002). High-grade gliomas had lower plasma BDNF (p = 0.0288). Tissue BDNF levels were higher in glioma patients (SMD: 1.9513; 95% CI: [0.7365, 3.1661], p = 0.0016) and correlated with tumor grade (p = 0.0122). Plasma BDNF levels negatively correlated with patient age (p = 0.0244) and positively with female percentage (p = 0.0007). BDNF is a promising biomarker in glioma, showing significant changes in plasma and tissue levels correlating with tumor grade, patient age, and gender.

Exercise training alters resting brain-derived neurotrophic factor concentration in older adults: A systematic review with meta-analysis of randomized-controlled trials.

This systematic review with meta-analysis investigated the effects of exercise training on brain-derived neurotrophic factor (BDNF) in older adults. Electronic databases of PubMed, Web of Science and Scopus were searched for studies investigating the effect of exercise training ≥4 weeks on resting BDNF levels in older adults. A standardized mean difference (SMD) was generated through random effects model. Thirty-five randomized-controlled trials met the inclusion criteria. Exercise training significantly increased resting BDNF levels [SMD = 0.56 (95 % CI 0.28 to 0.85)] both in plasma (SMD = 0.63) and serum (SMD = 0.54). Regarding exercise modality, aerobic (SMD = 0.48), resistance (SMD = 0.76) and combined exercise training (SMD = 0.55) increased BDNF levels. Exercise training with the duration of 12 weeks (SMD =0.65), moderate-to-vigorous (SMD = 0.83) and vigorous intensity (SMD = 0.71), and 3-4 sessions per week frequency (SMD = 0.78) yielded the largest effects on BDNF elevation. Since BDNF represents a fundamental contribution in neuronal processes and is linked to brain health, exercise training may help delay aging-related neuro-degenerative processes. REGISTRATION NUMBER: CRD42024499195.

The effect of ACTH/MSH N-terminal fragment analogs on the anxiety level, pain sensitivity and levels of neurotrophic factors BDNF and VEGF in primary neuronal cultures of rats

ACTH/MSH-like peptides (melanocortins) have a wide range of neurotropic effects, including effects on learning and memory processes, neuroprotection, emotional state and pain sensitivity. Present work is aimed to compare the effects of peptides, the structure of which includes a natural fragment of ACTH and a stabilizing tripeptide PGP. The peptides ACTH4-7PGP (Semax), ACTH6-9PGP и ACTH7-10PGP were used in the work. The effects of these peptides on the exploratory behavior, anxiety level and pain sensitivity of white rats, as well as on the protein levels of the neurotrophic factors BDNF (brain derived neurotrophic factor) and VEGF (vascular endothelial growth factor) in primary neuron cultures were studied. A comparative study of the effects of analogs of different ACTH/MSH fragments revealed both similarities and differences in their neurotropic activity. The peptides structure of which includes a sequence of ACTH4-7 or ACTH6-9 have nootropic, anxiolytic and analgesic activity, and also cause an increase in VEGF levels in the culture of hippocampal neurons. The peptide containing the ACTH7-10 sequence in the structure exhibits anxiolytic activity, increases exploratory behavior, does not affect pain sensitivity and has a stimulating effect on BDNF and VEGF levels in neuronal cultures. The data obtained indicate that different parts of the N-terminal region of the ACTH molecule are responsible for the manifestation of certain neurotropic effects of melanocortins. The results of the study can be used in the development of therapeutics based on natural melanocortins.

Hyperbaric Oxygen Therapy Increases Brain-Derived Neurotrophic Factor as well as Decreases Systemic Immune-Inflammatory Index and Systemic Inflammatory Response Index in Autism Spectrum Disorder

BACKGROUND: Neuroinflammation and immune dysregulation are frequently viewed as contributing factors of autism spectrum disorder (ASD). Brain-derived neurotrophic factor (BDNF) is involved in the maintenance of neuron viability, as well as in neuron differentiation. Meanwhile, Systemic Immune-Inflammatory Index (SII) and Systemic Inflammatory Response Index (SIRI) are basic hematological indices used to assess inflammation and immune status. Hyperbaric oxygen (HBO) is known to enhance cerebral blood flow and reduce inflammation, however, not many studies have observed the its effect on BDNF level, SII, and SIRI in ASD subjects; therefore, this study was performed.METHODS: Fifteen ASD subjects were involved in this study and received HBO therapy 10 times within a 2-week period. The HBO therapy was performed by letting the subjects got into an isolated chamber filled with 100% oxygen and 1.3 ATA pressure for 60 minutes. Pre- and post-therapy blood samples were taken from subjects. BDNF level was measured with Enzyme Linked Immunosorbent Assay (ELISA), while neutrophils, monocytes, lymphocytes and platelets were measured by hematology analyzer for the calculation of SII and SIRI.RESULTS: Post-therapy BDNF level was higher than pre-therapy (1.84 ng/mL vs. 1.46 ng/mL; p=0.039). The increased in BDNF suggested reduced neuroinflammation and enhanced connections between neurons. Both post-therapy SII (672.4 vs. 359.4; p=0.005) and SIRI (1.3 vs. 0.7; p=0.009) were significantly lower than pre-therapy indexes. Decreased in SII and SIRI signified a reduction in neuroinflammation.CONCLUSION: HBO therapy increases BDNF level, also decreases SII and SIRI in ASD subjects. These results suggest that HBO has an effect on neuroinflammation, specifically in ameliorating inflammation.KEYWORDS: autism spectrum disorder, BDNF, SII, SIRI, hyperbaric oxygen therapy

Protective effect of oleuropein on the brain tissue in D-Galactose-induced aging in rat model.

Oleuropein (OLE) has the potential to reduce oxidative stress and inflammation. So, in the present investigation, we explored the protective effect of OLE on brain aging induced by d-galactose (D-Gal) in a rat model. 40 Wister male adult rats were categorized into 5 groups. Group 1 received normal saline; group 2 was given 100mg/kg of D-Gal intraperitoneally (IP). The rats in groups 3 to 5 were given D-Gal (100mg/kg, IP) along with different doses of OLE (20, 40, and 80mg/kg, respectively) orally. All administrations were performed daily for 8 weeks. 24h after last treatment motor activity and memory impairment were evaluated. Then, the rats were euthanized and brain samples were collected for evaluating the levels of malondialdehyde (MDA), Brain-Derived Neurotrophic Factor (BDNF), protein carbonyl (PC), glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT), Superoxide dismutase (SOD), Tumor necrosis factor alpha (TNF-α), interleukin 1 beta ( IL-1β), as well as Sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1) gene expression. The results showed that D-Gal significantly reduced motor activity and memory performance (P < 0.05). It also significantly reduced the GPX, CAT and SOD activities, GSH and BDNF levels as well as SIRT1 and PGC1 expression, and, significantly increased PC, MDA TNF-α and IL-1β levels in the brain tissue (P < 0.05). Administration of OLE restored all of the above parameters close to control group. The findings demonstrated that OLE, through its antioxidant and anti-inflammatory properties, improved motor activity, memory impairment, and age-related neurological dysfunction.

Interaction between serum inflammatory cytokines and brain-derived neurotrophic factor in cognitive function among first-episode schizophrenia patients.

The pathogenesis of cognitive impairment in schizophrenia (SCZ) remains unclear. Accumulating studies showed that inflammatory-immune dysregulation and altered brain derived neurotrophic factor (BDNF) levels play a crucial role in the psychopathology of SCZ. However, their association with cognitive dysfunction in first-episode SCZ patients has not been thoroughly investigated. To explore the interaction effects between cognitive function and inflammatory cytokines and BDNF in first-episode SCZ. The current study is a cross-sectional case-control investigation that recruited 84 patients with first-episode SCZ (SCZ group) and 80 healthy controls (HCs group) at the Huzhou Third Municipal Hospital between August 2021 and September 2023. ELISA was employed to measure the serum levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, and BDNF. The Chinese brief cognitive test (C-BCT) and the positive and negative syndrome scales were measured the severity of cognitive impairment and psychiatric symptoms. Compared to the HC group, the SCZ group exhibited elevated IL-1β and IL-6 levels, decreased BDNF levels, and reduced C-BCT scores (all P < 0.001). In SCZ, BDNF was negatively correlated with IL-6 (r = -0.324, P < 0.05). Information processing speed was negatively correlated with IL-6 (r = -0.315, P < 0.05) and positively with BDNF (r = 0.290, P < 0.05); attention, working memory, comprehensive ability, and executive function were negatively correlated with IL-1β and IL-6 (all P < 0.05) and positively with BDNF (all P < 0.05). Multiple regression analysis showed IL-6 influenced C-BCT dimensions (β = -0.218 to -0.327, all P < 0.05); attention and executive ability were influenced by IL-1β (β = -0.199 to -0.261, all P < 0.05); comprehensive executive ability was influenced by BDNF (β = 0.209, P < 0.05). Our findings suggested that interrelationships between immune dysfunction and neurotrophic deficiency might underlie the pathological mechanisms of cognitive impairments in first-episode SCZ patients.

BDNF augmentation reverses cranial radiation therapy-induced cognitive decline and neurodegenerative consequences

Cranial radiation therapy (RT) for brain cancers is often associated with the development of radiation-induced cognitive dysfunction (RICD). RICD significantly impacts the quality of life for cancer survivors, highlighting an unmet medical need. Previous human studies revealed a marked reduction in plasma brain-derived neurotrophic factor (BDNF) post-chronic chemotherapy, linking this decline to a substantial cognitive dysfunction among cancer survivors. Moreover, riluzole (RZ)-mediated increased BDNF in vivo in the chemotherapy-exposed mice reversed cognitive decline. RZ is an FDA-approved medication for ALS known to increase BDNF in vivo. In an effort to mitigate the detrimental effects of RT-induced BDNF decline in RICD, we tested the efficacy of RZ in a cranially irradiated (9 Gy) adult mouse model. Notably, RT-exposed mice exhibited significantly reduced hippocampal BDNF, accompanied by increased neuroinflammation, loss of neuronal plasticity-related immediate early gene product, cFos, and synaptic density. Spatial transcriptomic profiling comparing the RT + Vehicle with the RT + RZ group showed gene expression signatures of neuroprotection of hippocampal excitatory neurons post-RZ. RT-exposed mice performed poorly on learning and memory, and memory consolidation tasks. However, irradiated mice receiving RZ (13 mg/kg, drinking water) for 6–7 weeks showed a significant improvement in cognitive function compared to RT-exposed mice receiving vehicle. Dual-immunofluorescence staining, spatial transcriptomics, and biochemical assessment of RZ-treated irradiated brains demonstrated preservation of synaptic integrity and mature neuronal plasticity but not neurogenesis and reduced neuroinflammation concurrent with elevated BDNF levels and transcripts compared to vehicle-treated irradiated brains. In summary, oral administration of RZ represents a viable and translationally feasible neuroprotective approach against RICD.

Dexmedetomidine Improves Learning Functions in Male Rats Modeling Cognitive Impairment by Modulating the BDNF/TrkB/CREB Signaling Pathway.

Dexmedetomidine (DEX) is a selective alpha-2 adrenergic receptor agonist with sedative and anxiolytic properties. Increasing evidence reports that DEX has a neuroprotective effect. In this study, we investigated the potential effects of DEX on learning and memory functions in rats with experimental cognitive impairment. In the study, 21 adult male rats were used. The rats were divided into three groups, namely control, Scopolamine (SCOP) and SCOP + DEX. Cognitive impairment was induced with 1 mg/kg SCOP daily for 21 days. DEX was administered at a dose of 10 µg/kg between days 14 and 21 of the experiment. Following the injections, a spatial memory test was performed with a Morris Water Maze (MWM). At the end of the experiment, the hippocampus was dissected. The brain-derived neurotrophic factor (BDNF), acetylcholine (ACh) and acetylcholinesterase (AChE) levels were determined by ELISA. The tropomyosin receptor kinase B (TrkB) and Cyclic AMP-Response Element-Binding Protein (CREB) levels were measured by immunohistochemistry. DEX treatment improved the learning performance of rats compared to SCOP for 5 days. However, it did not significantly change memory performance. DEX increased the BDNF and ACh levels in the hippocampus while decreasing the AChE levels. Similarly, DEX treatment significantly increased CREB phosphorylation. No significant difference was observed between the TrkB receptor levels of the groups. This study demonstrated that the role of DEX in reducing SCOP-induced cognitive impairment is partially mediated by the increase in BDNF/TrkB/CREB signaling pathway activity.

Revealing the Mechanism of Hemerocallis citrina Baroni in Depression Treatment Through Integrated Network Pharmacology and Transcriptomic Analysis.

Background/Objectives: Hemerocallis citrina Baroni (HCB) is a traditional herb for the treatment of depression in China. However, the active constituents and the underlying mechanisms of its antidepressant effects remain unclear. The aim of this study was to identify the bioactive constituents of HCB and elucidate its underlying mechanism for the treatment of depression. Methods: The constituents of HCB were systematically analyzed using UHPLC-Q-Orbitrap HRMS. Its antidepressant effect was evaluated by chronic unpredictable mild stress (CUMS)-induced depression. The mechanism of HCB in treating depression was investigated through network pharmacology and molecular docking. Subsequently, its potential mechanism for the treatment of depression was carried out by RNA sequencing. Finally, the mechanism was further verified by Western blot. Results: A total of 62 chemical constituents were identified from HCB using UHPLC-Q-Orbitrap HRMS, including 17 flavonoids, 11 anthraquinones, 11 alkaloids, 10 caffeoylquinic acid derivatives, five phenolic acids, five triterpenoids, and three phenylethanosides, 13 of which were identified as potential active constituents targeting 49 depression-associated proteins. Furthermore, HCB was found to significantly reduce cognitive impairment, anxiety-like behavior, and anhedonia-like behavior. The expression levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF) were elevated in the hippocampal CA3 region. Results from network pharmacology and transcriptomics indicated that the PI3K/Akt/CREB signaling pathway is essential for the therapeutic effects of HCB on depression. Research in the field of molecular biology has conclusively demonstrated that HCB is associated with an increase in the expression levels of several important proteins. Specifically, there was a notable upregulation of phosphorylated PI3K (p-PI3K) relative to its unphosphorylated form PI3K, as well as an elevation in the ratio of phosphorylated Akt (p-Akt) to total Akt. Additionally, the study observed increased levels of phosphorylated CREB (p-CREB) compared to its unphosphorylated CREB. Conclusions: This study provides compelling evidence that HCB possesses the ability to mitigate the symptoms of depression through its influence on the PI3K/Akt/CREB signaling pathway. HCB could be developed as a promising therapeutic intervention for individuals struggling with depression, offering new avenues for treatment strategies that target this particular signaling mechanism.

Dietary Patterns, Serum BDNF and Fatty Acid Profiles in Physically Active Male Young Adults: A Cluster Analysis Study.

Background/Objectives: Although physical activity and balanced diet may increase peripheral brain-derived neurotrophic factor (BDNF) concentration, little is known about whether these factors modify BDNF content in physically active individuals and whether the serum fatty acid (FA) profile is related. This study aimed to evaluate quality of diet, identify specific dietary patterns and assess their influence on BDNF and FA levels in serum. It is hypothesized that there is a correlation between diet quality and the concentrations of BDNF and FA in the serum of physically active male individuals. Methods: Physically active young adult male students at Jozef Pilsudski University of Physical Education in Warsaw (Poland) were enrolled. Dietary patterns were identified with cluster analysis and linear discriminant analysis (LDA) based on responses to a validated food frequency questionnaire, KomPAN® version 1.1. Results: Consumption of beverages, vegetables, milk, wholemeal bread/rolls, fruit and vegetable juices, butter, tinned vegetables and fruits were significant in the LDA model, in which three clusters were distinguished. Cluster 1 was characterized by more frequent consumption of wholemeal bread/rolls, milk, fruits, vegetables, fruit and vegetable juices and sweetened hot beverages and by significantly greater values for the pro-healthy diet index (p < 0.0001) and diet quality index (p < 0.0001) compared to Clusters 2 and 3. The diet of Cluster 2 was of the worst quality, as indicated by the higher values of the not-healthy diet index. Cluster 1 had the tendency for the highest BDNF levels (of the best quality of diet), and a tendency for decreased BDNF concentration with an increased physical activity level was observed. Conclusions: Physical activity, diet quality and BDNF level depend, correlate and interact with each other to provide both optimal physical and mental health.

Hippocampal Viral-Mediated Urokinase Plasminogen Activator (uPA) Overexpression Mitigates Stress-Induced Anxiety and Depression in Rats by Increasing Brain-Derived Neurotrophic Factor (BDNF) Levels.

Emerging evidence suggests the serine protease, urokinase plasminogen activator (uPA), may play an important role in the modulation of mood and cognitive functions. Also, preliminary evidence indicates that uPA modulates BDNF activity that is known to be involved in the pathogenesis of mood disorders. However, the physiological functions of uPA in specific brain regions for mediating stress-related emotional behaviors remain to be elucidated. Therefore, the aim of this study was to assess the role of ectopic uPA expression on anxiety- and depression-like behaviors following social defeat stress in rats. For this purpose, we inspected the behavioral outcomes following bilateral stereotaxic delivery of uPA-overexpressing lentiviral vectors in the hippocampus using a series of behavioral tests. Results show that hippocampal uPA gain-of-function prevented stress-elicited anxiogenic-like effects, as determined in the marble burying, open field, and elevated plus maze tests, with no alterations in spontaneous locomotor activity. Also, ectopic uPA overexpression resulted in anti-depressant-like effects in the sucrose splash, tail suspension, and forced swim tests. Most importantly, uPA overexpression increased hippocampal BDNF levels, and a strong positive correlation was found using the Pearson test. Moreover, the same correlation analysis revealed a strong negative relationship between uPA mRNA and parameters of anxiety- and depression-like behaviors. Taken together, this work highlights the importance of considering uPA activation and provides new insights into the mechanisms involved in the pathophysiology of stress-elicited mood illnesses, which should help in the development of new approaches to tackle depression and anxiety disorders.

Neuroplasticity in Depressive Disorders: The Role of BDNF in Linking Pharmacotherapy and Physical Activity

Introduction: Depressive disorders are among the most prevalent mental health conditions globally, affecting millions of people. Despite extensive research, the exact pathophysiology of depression remains unclear. Recent evidence suggests that neuroplasticity, particularly the role of brain-derived neurotrophic factor (BDNF), plays a crucial role in both the onset and treatment of depressive disorders. Aim of Study: This review explores the relationship between neuroplasticity and depression, focusing on BDNF as a central biomarker and potential therapeutic target. It also examines how antidepressant therapies and physical activity influence neuroplasticity and BDNF levels, offering insights into novel approaches for treating depressive disorders. Material and Methods: A literature review was conducted using PubMed and Google Scholar databases, focusing on peer-reviewed articles with the keywords: "neuroplasticity", "BDNF", "depression", "antidepressants" and "physical activity". Conclusions: Neuroplasticity, particularly through BDNF signaling, plays a critical role in the pathogenesis and treatment of depression. Elevated BDNF levels promote synaptic plasticity, neurogenesis, and recovery of brain function. Antidepressant treatments enhance neuroplasticity by increasing BDNF levels. Antidepressants and physical activity both influence neuroplastic processes, with BDNF serving as a key mediator.

Light Treatment Ameliorates Sub-chronic MK-801-Induced Cognitive Deficits in Mice Through Up-regulating BDNF/p-CREB/p-ERK Signaling Pathway.

Cognitive impairment associated with schizophrenia (CIAS) is considered a core symptom of the illness, yet effective treatments remain limited. Light plays an important role in regulating cognitive functions. However, the potential of light treatment (LT) to improve CIAS remains unknown. The current study aimed to investigate the efficacy of LT on CIAS and explore the underlying molecular mechanisms in a CIAS animal model. The CIAS group and the control group were sub-chronically administered MK-801 and saline, respectively. Concurrently, the LT/CIAS group, consisting of CIAS mice, received LT exposure (3000 Lux, 2h/day, for 3weeks). Results showed a significant enhancement in cognitive performance among LT/CIAS mice, as evidenced by improvements in the novel object recognition (NOR) test, novel location recognition (NLR) test, and Morris water maze (MWM) compared to the CIAS group. Remarkably, these beneficial effects of LT persisted for over 4weeks after the termination of LT. Furthermore, Golgi-cox staining unveiled an increased dendritic spine density and enhanced morphological complexity in hippocampal CA1 pyramidal neurons following 3weeks of LT. Subsequent investigations revealed elevated levels of brain-derived neurotrophic factor (BDNF) and heightened phosphorylation of cAMP response element-binding phosphorylation protein (p-CREB) in the hippocampus of the LT/CIAS group compared to the CIAS group. Moreover, LT elevated the phosphorylated extracellular signal-regulated kinase (p-ERK) in the hippocampus of the LT/CIAS group relative to the CIAS group. In conclusion, the current study demonstrates that long-term LT effectively ameliorated sub-chronic MK-801-induced cognitive deficits in mice, and the altered dendritic spine density and morphology of CA1 pyramidal neurons were rescued in the LT/CIAS group, potentially through the up-regulation of the BDNF/p-CREB/p-ERK signaling pathway in LT/CIAS mice.

Genetic determinants of serum brain-derived neurotrophic factor (BDNF) after alcohol withdrawal

Peripheral brain-derived neurotrophic factor (BDNF) levels increase during alcohol abstinence in dependent subjects. Meanwhile, the genetic determinants of circulating BDNF this context are poorly understood. Studies of associations between circulating BDNF and single nucleotide polymorphisms (SNPs) of the corresponding gene are mainly restricted by the most studied BDNF SNP rs6265. A recent genome-wide association study demonstrated that the BDNF-related SNP rs75945125 is associated with serum BDNF. However, it is unknown whether this SNP is associated with changes in peripheral BDNF levels in the context of alcohol abstinence. We aimed to assess the association of the BDNF-related SNPs rs75945125 and rs6265 with changes in serum BDNF levels after alcohol withdrawal and the corresponding clinical manifestations. A total of 132 inpatients diagnosed with alcohol withdrawal syndrome were enrolled in the study. Serum BDNF levels were assessed on 2nd, 7th, and 21st days after alcohol withdrawal. Alcohol withdrawal syndrome severity, craving severity, affective symptoms, and cognitive impairment were assessed on 7th and 21st days. BDNF SNPs rs75945125 and rs6265 were genotyped using real-time PCR. BDNF concentrations in the carriers of the rs75945125 C allele on 21st day were higher as compared with TT genotype carriers. BDNF SNP rs75945125 C allele carriers had a longer duration of problem drinking, consumed a lesser volume of alcohol in the last 3 months, and had lower severity of withdrawal syndrome on 7th day compared with TT genotype carriers. BDNF levels were moderated by rs75945125 and rs6265, as well as by the interaction of rs75945125 × rs6265, whereas only the interaction of rs75945125 × rs6265 had an effect on depression scores during abstinence. Thus, the trajectory of serum BDNF changes during alcohol abstinence is determined by both rs75945125 and rs6265. Moreover, BDNF gene-related SNPs are associated with the clinical parameters of alcohol dependence and withdrawal. The longitudinal design without a control group and the relatively small sample size are the limitations of this study. Future studies on the revealed interactions are warranted.