Search Results (1,251)

Adolescence represents a critical period of neurodevelopment during which brain-derived neurotrophic factor (BDNF) plays a fundamental role in neuronal survival and synaptic plasticity. While exercise-BDNF relationships are well-documented in adults, evidence in adolescents remains limited and inconsistent. This systematic review examined the effects of exercise modalities on circulating BDNF concentrations in adolescent populations. A systematic search was conducted following PRISMA guidelines across multiple databases (FECYT, PubMed, SPORTDiscus, ProQuest Central, SCOPUS, Cochrane Library) through June 2025. Inclusion criteria comprised adolescents, exercise interventions, BDNF outcomes, and randomized controlled trial design. Methodological quality was assessed using the PEDro scale. From 130 initially identified articles, 8 randomized controlled trials were included, with 4 rated as excellent and the other 4 as good quality. Exercise modalities included aerobic, resistance, concurrent, high-intensity interval training, Taekwondo, and whole-body vibration, with durations ranging 6–24 weeks. Four studies demonstrated statistically significant BDNF increases following exercise interventions, four showed no significant changes, and one reported transient reduction. Positive outcomes occurred primarily with vigorous-intensity protocols implemented for a minimum of six weeks. Meta-analysis was not feasible due to high heterogeneity in populations, interventions, and control conditions. Moreover, variation in post-exercise sampling timing further limited comparability of BDNF results. Future research should standardize protocols and examine longer interventions to clarify exercise-BDNF relationships in adolescents. Full article

Stress is a major factor that threatens the body’s homeostasis or well-being. Excessive stress causes psychological anxiety and tension, which disrupts the balance of the autonomic nervous system that maintains the body’s balance, resulting in hormonal imbalance and brain changes. In this study, we investigated the effects of Withania somnifera (Ashwagandha) extract on depression, neurobehavior, and hippocampal changes in model mice exposed to stress. Using an excessive restraint stress-induced depression model, we measured the behavioral changes and the levels of brain-derived neurotrophic factor (BDNF) and antioxidant genes in five groups: control, stress, low-dose W. somniferous extract (20 mg/kg/day), high-dose W. somniferous extract (40 mg/kg/day), and L-theanine (50 mg/kg/day, positive control). Stressed mice showed poorer performance in the open field and elevated plus maze tests compared with the control group. The impaired performance was restored following W. somniferous extract administration. In addition, W. somniferous extract restored the decreased expression of BDNF in the hippocampus caused by restraint stress, improved the balance of stress hormones (i.e., cortisol, dopamine, and norepinephrine), and also regulated BDNF, inflammatory genes, and antioxidant genes in brain tissue. Therefore, W. somniferous extract can induce antidepressant and anti-stress effects by maintaining brain BDNF expression and preventing hippocampal tissue alterations caused by restraint stress. Full article

Benign prostatic hyperplasia (BPH) is a multifactorial condition that is highly prevalent and affects aging males. It frequently results in lower urinary tract symptoms (LUTS) and a reduced quality of life. While hormonal dysregulation and chronic inflammation have long been implicated in BPH pathogenesis, recent evidence highlights the role of physical activity in modulating prostate health. In this narrative review, evidence from quantitative studies examining the effect of exercise on BPH risk and symptom severity was first synthesized. Collectively, these studies suggest that regular physical activity is associated with a lower incidence and reduced progression of BPH. The potential mechanisms through which exercise may exert protective effects on the prostate were then explored. These include modulation of sympathetic nervous system activity, alterations in hormonal profiles (e.g., testosterone and insulin), suppression of chronic inflammation and oxidative stress, and the promotion of autophagy within prostatic tissue. Central to these mechanisms is the role of myokines—signaling molecules secreted by skeletal muscle during exercise. Key myokines, such as irisin, interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and myostatin, are reviewed in the context of prostate health. These molecules regulate inflammatory pathways, metabolic processes, and tissue remodeling. For instance, exercise-induced reductions in myostatin are linked to improved insulin sensitivity and decreased fat accumulation, while elevated irisin and BDNF levels may exert anti-inflammatory and metabolic benefits relevant to BPH pathophysiology. Although direct causal evidence linking myokines to BPH is still emerging, their biological plausibility and observed systemic effects suggest a promising avenue for non-pharmacological intervention. Future research should focus on identifying the specific myokines involved, elucidating their molecular mechanisms within the prostate, and evaluating their therapeutic potential in clinical trials. Full article

As the global population continues to age, the incidence of neurodegenerative diseases and neural injuries is increasing, presenting major challenges for healthcare systems. Due to the brain’s limited regenerative capacity, there is an urgent need for strategies that promote neuronal repair and functional integration. Brain-derived neurotrophic factor (BDNF) is a key regulator of synaptic plasticity and neuronal development. In this study, we investigated whether constitutive BDNF expression in human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) enhances their neurogenic and integrative potential in vitro. We found that NPCs engineered to overexpress BDNF produced neuronal cultures with increased numbers of mature and spontaneously active neurons, without altering the overall structure or organization of functional networks. Furthermore, BDNF-expressing neurons exhibited significantly greater axonal outgrowth, including directed axon extension in a compartmentalized microfluidic system, suggesting a chemoattractive effect of localized BDNF secretion. These effects were comparable to those observed with the early supplementation of recombinant BDNF. Our results demonstrate that sustained BDNF expression enhances neuronal maturation and axonal projection without disrupting network integrity. These findings support the use of BDNF not only as a therapeutic agent to improve cell therapy outcomes but also as a tool to accelerate the development of functional neural networks in vitro. Full article

Background: Accelerated demographic aging in Hungary and across Europe presents significant public health and socioeconomic challenges, particularly in preserving cognitive function and preventing neurodegenerative diseases. Modifiable lifestyle factors—especially dietary habits—play a critical role in brain aging and cognitive decline. Objective: This narrative review explores the mechanisms by which Western dietary patterns contribute to cognitive impairment and neurovascular aging, with specific attention to their relevance in the Hungarian context. It also outlines the rationale and design of the Semmelweis Study and its workplace-based health promotion program targeting lifestyle-related risk factors. Methods: A review of peer-reviewed literature was conducted focusing on Western diet, cognitive decline, cerebrovascular health, and dietary interventions. Emphasis was placed on mechanistic pathways involving systemic inflammation, oxidative stress, endothelial dysfunction, and decreased neurotrophic support. Key findings: Western dietary patterns—characterized by high intakes of saturated fats, refined sugars, ultra-processed foods, and linoleic acid—are associated with elevated levels of 4-hydroxynonenal (4-HNE), a lipid peroxidation product linked to neuronal injury and accelerated cognitive aging. In contrast, adherence to Mediterranean dietary patterns—particularly those rich in polyphenols from extra virgin olive oil and moderate red wine consumption—supports neurovascular integrity and promotes brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) activity. The concept of “cognitive frailty” is introduced as a modifiable, intermediate state between healthy aging and dementia. Application: The Semmelweis Study is a prospective cohort study involving employees of Semmelweis University aged ≥25 years, collecting longitudinal data on dietary, psychosocial, and metabolic determinants of aging. The Semmelweis–EUniWell Workplace Health Promotion Model translates these findings into practical interventions targeting diet, physical activity, and cardiovascular risk factors in the workplace setting. Conclusions: Improving our understanding of the diet–brain health relationship through population-specific longitudinal research is crucial for developing culturally tailored preventive strategies. The Semmelweis Study offers a scalable, evidence-based model for reducing cognitive decline and supporting healthy aging across diverse populations. Full article

Background and Aims: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease frequently associated with fatigue and mild cognitive impairment. Brain-derived neurotrophic factor (BDNF) plays key roles in neuroplasticity, immune regulation, and metabolism. This study aimed to evaluate plasma BDNF levels in early-stage PBC and examine their clinical and biochemical associations. Methods: In this observational study, plasma BDNF, IL-6, and IL-18 concentrations were measured by ELISA in 45 patients with early-stage PBC and 31 age- and sex-matched healthy controls (mean age 60.5 years; 96% women). All participants underwent liver elastography using point shear wave elastography (ElastPQ), Doppler ultrasound, laboratory testing, and assessment of cognitive function (PHES) and fatigue severity (MFIS). Non-invasive fibrosis scores (APRI, FIB-4) were calculated. Results: Median plasma BDNF concentrations were significantly higher in PBC patients than in controls [median: 21.04 ng/mL (IQR: 10.68–38.07) vs. 5.80 ng/mL (IQR: 4.58–7.54); p < 0.0001]. In PBC patients, higher BDNF levels correlated inversely with liver stiffness measured by ElastPQ (R = −0.39, p = 0.0258), spleen dimensions, splenic vein flow volume (R = −0.49, p = 0.0018), suggesting an association with milder liver fibrosis and early hemodynamic alterations. A trend toward association between BDNF and IL-6 levels was observed in multivariate analysis. No significant associations were found between BDNF concentrations and markers of hepatocellular injury, cognitive performance, or fatigue severity. Conclusions: Plasma BDNF concentrations are elevated in early-stage PBC and inversely correlate with liver fibrosis severity. No significant associations were found with hepatocellular injury, cognitive function, or fatigue. These findings suggest that BDNF may play a protective role against hepatic fibrogenesis, or alternatively, that BDNF concentrations may decline with advancing liver disease. Further studies are needed to clarify its significance in PBC. Full article

Brain-derived neurotrophic factor (BDNF) is associated with nicotine use behaviours, the intensity of nicotine cravings, and the experience of withdrawal symptoms. Given the established influence of sex, brain-derived neurotrophic factor variants, personality traits and anxiety levels on nicotine use, this study aimed to conduct a comprehensive association analysis of these factors within a cohort of women who use nicotine. The study included 239 female participants: 112 cigarette users (mean age = 29.19, SD = 13.18) and 127 never-smokers (mean age = 28.1, SD =10.65). Study participants were examined using the NEO Five-Factor Inventory and the State–Trait Anxiety Inventory. Genotyping of rs6265, rs10767664, and rs2030323 was performed by real-time PCR using an oligonucleotide assay. We did not observe significant differences in the distribution of either genotype or allele of rs6265, rs10767664 and rs2030323 between groups. However, compared to the never-smokers, cigarette users scored significantly lower on the Agreeableness (5.446 vs. 6.315; p = 0.005767; d_Cohen’s = 0.363; η² = 0.032) and the Conscientiousness (5.571 vs. 6.882; p = 0.000012; d_Cohen’s = 0.591; η²= 0.08) scales. There was significant linkage disequilibrium between all three analysed polymorphic variants—between rs6265 and rs10767664 (D′ = 0.9994962; p < 2.2204 × 10⁻¹⁶), between rs6265 and rs2030323 (D′ = 0.9994935; p < 2.2204 × 10⁻¹⁶) and between rs10767664 and rs20330323 (D′ = 0.9838157; p < 2.2204 × 10⁻¹⁶), but the haplotype association analysis revealed no significant differences. While our study did not reveal an association between the investigated brain-derived neurotrophic factor polymorphisms (rs6265, rs10767664 and rs2030323) and nicotine use, it is essential to acknowledge that nicotine dependence is a complex, multifactorial phenotype. Our study expands the current knowledge of BDNF ’s potential role in addictive behaviours by exploring the understudied variants (rs10767664 and rs2030323), offering a novel contribution to the field and paving the way for future research into their functional relevance in addiction-related phenotypes. The lower Agreeableness and Conscientiousness scores observed in women who use nicotine compared to never-smokers suggest that personality traits play a significant role in nicotine use in women. The observed relationship between personality traits and nicotine use lends support to the self-medication hypothesis, suggesting that some women may initiate or maintain nicotine use as a coping mechanism for stress and negative affect. Public health initiatives targeting women should consider personality and psychological risk factors in addition to biological risks. Full article

Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene expression profile in the frontal cortex and hippocampus (HPC) that are relevant to social and attentional/cognitive schizophrenia-linked symptoms; on the other hand, RLA rats display phenotypic traits linked to increased anxiety and sensitivity to stress-induced depression-like behaviours. The present studies aimed to evaluate the enduring and potentially positive effects of neonatal handling-stimulation (NH) on the traits differentiating these two strains of rats. Methods: We evaluated the effects of NH on anxious behaviour, prepulse inhibition of startle (PPI), spatial working memory, and hormone responses to stress in adult rats of both strains. Furthermore, given the proposed involvement of neuronal/synaptic plasticity and neurotrophic factors in the development of anxiety, stress, depression, and schizophrenia-related symptoms, using Western blot (WB) we assessed the effects of NH on the content of brain-derived neurotrophic factor (BDNF), its trkB receptor and Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the prefrontal cortex (PFC), anterior cingulate cortex (ACg), ventral (vHPC), and dorsal (dHPC) hippocampus of adult rats from both strains. Results: NH increased novelty-induced exploration and reduced anxiety, particularly in RLA rats, attenuated the stress-induced increment in corticosterone and prolactin plasma levels, and improved PPI and spatial working memory in RHA rats. These effects correlated to long-lasting increases of BDNF and PSA-NCAM content in PFC, ACg, and vHPC. Conclusions: Collectively, these findings show enduring and distinct NH effects on neuroendocrine and behavioural and cognitive processes in both rat strains, which may be linked to neuroplastic and synaptic changes in the frontal cortex and/or hippocampus. Full article

Background/Objectives: Daily caloric restriction (DCR) is a common dietary weight loss strategy, but leads to metabolic and behavioral adaptations, including maladaptive eating behaviors and dysregulated appetite. Intermittent fasting (IMF) may mitigate these effects by offering diet flexibility during energy restriction. This secondary analysis compared changes in eating behaviors and appetite-related hormones between 4:3 intermittent fasting (4:3 IMF) and DCR and examined their association with weight loss over 12 months. Methods: Adults with overweight or obesity were randomized to 4:3 IMF or DCR for 12 months. Both randomized groups received a matched targeted weekly dietary energy deficit (34%), comprehensive group-based behavioral support, and a prescription to increase moderate-intensity aerobic activity to 300 min/week. Eating behaviors were assessed using validated questionnaires at baseline and months 3, 6, and 12. Fasting levels of leptin, ghrelin, peptide YY, brain-derived neurotrophic factor, and adiponectin were measured at baseline and months 6 and 12. Linear mixed models and Pearson correlations were used to evaluate outcomes. Results: Included in this analysis were 165 adults (mean ± SD; age 42 ± 9 years, BMI 34.2 ± 4.3 kg/m², 74% female) randomized to 4:3 IMF (n = 84) or DCR (n = 81). At 12 months, binge eating and uncontrolled eating scores decreased in 4:3 IMF but increased in DCR (p < 0.01 for between-group differences). Among 4:3 IMF, greater weight loss was associated with decreased uncontrolled eating (r = −0.27, p = 0.03), emotional eating (r = −0.37, p < 0.01), and increased cognitive restraint (r = 0.35, p < 0.01) at 12 months. There were no between-group differences in changes in fasting appetite-related hormones at any time point. Conclusions: Compared to DCR, 4:3 IMF exhibited improved binge eating and uncontrolled eating behaviors at 12 months. This may, in part, explain the greater weight loss achieved by 4:3 IMF versus DCR. Future studies should examine mechanisms underlying eating behavior changes with 4:3 IMF and their long-term sustainability. Full article

Dysregulated inflammatory processes contribute to depression, and gene–environment interactions may influence an individual’s risk and resilience. Reduced brain-derived neurotrophic factor (BDNF) expression increases susceptibility for developing depressive symptoms, and the Val66Met (rs6265) single-nucleotide polymorphism (SNP) on the BDNF gene is linked to mood disorders. However, whether Val66Met confers increased vulnerability to inflammation-induced depressive tendencies is unknown. Here, we tested the hypothesis that the Val66Met SNP increases vulnerability to inflammation-induced depressive symptoms in a mouse model of lipopolysaccharide (LPS)-induced depression-like behavior. Behavior and neuroinflammation, following a 24 h LPS challenge, were measured in mice expressing the human BDNF Val66Met gene variant or Val66Val littermates (control). The Val66Met genotype did not affect the peripheral inflammatory response, acute neuroinflammation, or the acute sickness behavior response. Val66Met mice exhibited anhedonia-like behavioral responses following LPS challenge, and we found increased mRNA expression of IL-1β and TNFα in the cerebrum compared to controls. The mRNA expression of IL-1β and TNFα in the hippocampus and the nucleus accumbens of Val66Met mice was increased following LPS, and a significant genotype × LPS interaction was detected for CD68 expression in the nucleus accumbens. In summary, these data suggest that immune activation in Val66Met mice increased susceptibility to anhedonic behavior and dysregulated negative regulation of inflammation. Full article

Background: Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuroplasticity and cognitive development. While exercise has been shown to modulate BDNF levels in adults, evidence in children remains limited and heterogeneous. Methods: A systematic review was conducted following PRISMA guidelines to examine randomized controlled trials investigating exercise effects on BDNF in children aged 5–12 years. The databases searched included FECYT, PubMed, SPORTDiscus, ProQuest Central, SCOPUS, and Cochrane Library through June 2025. Study quality was assessed using the PEDro scale. Results: Five randomized controlled trials (N = 385 participants) met inclusion criteria. Two studies (40%) demonstrated significant BDNF increases following exercise interventions. Successful interventions were characterized by neuromotor activities or martial arts programs, training frequencies ≥ 3 sessions/week, durations ≥ 12 weeks, and healthy participant populations. Methodological quality was mostly fair, with four studies rated as fair and one as good. Conclusions: Structured physical exercise may enhance BDNF levels in healthy children, with neuromotor activities and martial arts showing particular promise. However, children with overweight/obesity may require modified intervention approaches. The evidence supports the implementation of cognitively engaging physical activities in educational settings to optimize brain health during critical developmental periods, though larger standardized trials are needed to strengthen these preliminary findings. Full article

Background: To identify drug candidates that reduce cellular stress, linear peptides known as endomorphin (EM) analogs containing proline surrogates in position 2 were tested in in vitro injury models induced by corticosterone (CORT). Methods: In this study, neuroblastoma (SH-SY5Y) cells were treated with CORT and synthesized peptides, and then the cell viability and morphology, reactive oxygen species production (ROS), mitochondrial membrane potential (ΔΨm), adenosine triphosphate (ATP), and intracellular calcium ion [Ca²⁺]_i levels were evaluated. We also conducted an in-depth analysis of the apoptosis markers using quantitative real-time PCR (qPCR). Finally, we explore the brain-derived neurotrophic factor (BDNF) expression (qPCR) and protein levels (ELI-SA and Western blot). Results: The strongest neuroprotective effect in the CORT-induced stress model was shown by peptide 3 and peptide 7 (in the following sequence Tyr-Inp-Trp-Phe-NH2 and Tyr-Inp-Phe-Phe-NH2, respectively). These peptides significantly improved cell viability and reduced oxidative stress in CORT-treated cells. Conclusions: Their neuroprotective potential appears linked to anti-apoptotic effects, along with in-creased BDNF expression. Moreover, in the lipopolysaccharide (LPS)- and interferon-γ (IFN-γ)-induced damage model in macrophage RAW 264.7 cells, these two peptides reduced the secretion of inflammatory mediators nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Peptides exhibiting both neuroprotective and anti-inflammatory properties warrant further investigation as potential therapeutic agents. Full article

Background: This study aimed to compare the immediate effects of small-sided games (SSGs) and running-based high-intensity interval training (HIITrb) on serum brain-derived neurotrophic factor (BDNF) levels, cognitive performance, and enjoyment in young, male soccer players. Methods: Twenty-four soccer players [age: 19.2 ± 0.8 years] completed one session each of four-a-side SSG or HIITrb in a randomized, counterbalanced, and crossover design, with a one-week washout period. Blood samples and Trail Making Tests (TMTs) A and B were measured before and after exercise. Heart rate (HR) was monitored throughout the games, and ratings of perceived exertion (RPE) and enjoyment were collected at the end of the measurements. Results: The results show no significant effects of time (p > 0.775), group (p > 0.276) or time × group interaction (p > 0.199) on BDNF levels. For TMT-A, the time effect (p = 0.866) and group effect (p = 0.057) were not significant; however, the time × group interaction was significant (p < 0.019), indicating a superior performance in the SSG compared to HIITrb. In the TMT-B, significant effects were observed for both time (p < 0.001) and group (p < 0.001), while the time × group interaction effect was not statistically significant (p > 0.061). Furthermore, enjoyment levels did not differ significantly between conditions (p = 0.976). Conclusions: These findings suggest that four-a-side SSG may enhance processing speed compared to HIITrb without changes in serum BDNF levels. Coaches may consider using 4v4 SSG formats in early training sessions or warm-ups to stimulate processing speed and mental readiness in young soccer players. Full article

In this study, we identify cortical molecular biomarkers potentially associated with learning in mice using artificial intelligence (AI), inclusive of established and novel feature selection combined with supervised learning technologies. We applied multiple machine learning (ML) algorithms, using public domain ML software, to a public domain dataset, in order to support reproducible findings. We developed technologies tasked with predicting whether a given mouse was shocked to learn, based on protein expression levels extracted from their cortices. Results indicate that it is possible to predict whether a mouse has been shocked to learn or not based only on the following cortical molecular biomarkers: brain-derived neurotrophic factor (BDNF), NR2A subunit of N-methyl-D-aspartate receptor, B-cell lymphoma 2 (BCL2), histone H3 acetylation at lysine 18 (H3AcK18), protein kinase R-like endoplasmic reticulum kinase (pERK), and superoxide dismutase 1 (SOD1). These results were obtained with a novel redundancy-aware feature selection method. Five out of six protein expression biomarkers (BDNF, NR2A, H3AcK18, pERK, SOD1) identified have previously been associated with aspects of learning in the literature. Three of the proteins (BDNF, NR2A, and BCL2) have previously been associated with pruning, and one has previously been associated with apoptosis (BCL2), implying a potential connection between learning and both cortical pruning and apoptosis. The results imply that these six protein expression profiles (BDNF, NR2A, BCL2, H3AcK18, pERK, SOD1) are highly predictive of whether or not a mouse has been shocked to learn. Full article

Nerve tissue damage is an unsolved problem in modern neurology and neurosurgery, which prompts the need to search for approaches to stimulate neuroprotection and regeneration of neural tissue. Earlier we have shown that the secretome of human mesenchymal stromal cells (MSCs) stimulates rat survival, reduces the severity of neurological deficits, and decreases the volume of brain damage in a hemorrhagic stroke model. A significant disadvantage of using the MSC secretome is the need to concentrate it (at least 5–10 fold) to achieve appreciable pharmacological activity. This increases the cost of obtaining clinically applicable amounts of secretome and slows down the clinical translation of this technology. Here, we created a number of genetically modified human MSC cultures, including immortalized MSCs and those with hyperexpression of brain-derived neurotrophic factor (BDNF) and urokinase-type plasminogen activator (uPA) and with suppressed expression of Von Hippel–Lindau tumor suppressor (VHL), and we evaluated the pharmacological activity of their secretomes in a model of intracerebral hemorrhage (ICH) in rats. The secretome of MSCs immortalized by hyperexpression of the catalytic subunit of human telomerase (hTERT) revealed neuroprotective activity indistinguishable from that of primary MSC cultures, yet it still required 10-fold concentration to achieve neuroprotective efficacy. The secretome of MSC culture with combined hyperexpression of BDNF and uPA and suppressed expression of Von Hippel–Lindau tumor suppressor even without additional concentration reduced the severity of neurological disorders and decreased brain lesion volume in the ICH model. The secretomes of MSCs with separate overexpression of BDNF and uPA or suppression of VHL had no such effect or, on the contrary, revealed a toxic effect in the ICH model. Presumably, this may be due to an imbalance in the representation of individual growth factors in the secretome of genetically modified MSCs, which individually may lead to undesirable effects in damaged nervous tissue, such as increased permeability of the blood–brain barrier (under the influence of pro-angiogenic factors) or neural cell apoptosis (due to an excess of neurotrophic factors). The obtained data show that genetic modification of MSC cultures can enhance or alter the therapeutic activity of their secretomes, which can be used in the creation of promising sources of biopharmaceutical substances. Full article