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This pilot study investigated the protective effect of transfecting brain-derived neurotrophic factor (BDNF) and B-cell lymphoma 2 (bcl-2) genes in retinal ganglion cells (RGCs) using in vivo electroporation in an adult rat optic nerve transection model. Sprague-Dawley rats were randomly divided into five groups: BDNF(+)/bcl-2(+), BDNF(+), bcl-2(+), empty plasmid (EP), and no surgery (NS). The plasmids were intravitreally injected and electroporated into the left eye. Seven days later, optic nerve transection was performed in all groups except the NS group. Protein expression was examined using Western blotting, RGC survival was quantified using 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) retrograde labeling, and apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) at multiple time points (7, 14, and 28 d after transfection). A significantly higher number of DiI (+) RGCs and lower number of apoptotic cells were observed in the BDNF(+)/bcl-2(+), BDNF(+), and bcl-2(+) groups compared to those in the EP group at all time points. The number of DiI (+) RGCs in the three treatment groups was significantly lower than that in the NS group. However, there were no significant differences among the three treatment groups. The protective effects of gene transfection tended to be strongest in the BDNF(+)/bcl-2(+) group, followed by the BDNF(+) group and then the bcl-2(+) group. Thus, all gene transfection treatments had a protective effect against the loss of DiI(+) RGCs induced by optic nerve transection but did not result in full recovery. This study also confirmed the value of in vivo electroporation. The findings of this pilot study provide a working base for the development of gene therapy for blinding optic nerve disorders. Show less

Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) are neurodegenerative disorders with marked neuronal dysfunction and damage, accompanied by the accumulation of abnormal alpha-synuclein. Identifying the proteins involved in their specific neurodegenerative processes is important to understand shared or disease-specific mechanisms of neurodegeneration. Recent investigations into these disorders have revealed intriguing alterations in the functionality of neurotrophic factors, including and predominantly the Brain-Derived Neurotrophic Factor (BDNF). Thus, the aim of this study was to investigate the BDNF serum levels in two cohorts of DLB and MSA patients and compare them to those of healthy individuals. Investigating serum BDNF concentrations in these conditions may provide insights into aspects of the underlying mechanisms of neurodegeneration. Serum BDNF concentrations were determined using commercial enzyme-linked immunosorbent assays. All serum samples were tested in duplicate, and the reported BDNF concentrations were ng/ml. The findings demonstrated a significant increase in serum BDNF levels in both DLB and MSA patients versus healthy subjects. This increase may represent a compensatory neuroprotective response to ongoing neuronal damage or a reflection of disease-related pathophysiological mechanisms involving altered BDNF regulation. These findings contribute to a growing body of evidence implicating neurotrophic fac-tor dysregulation in the pathogenesis of α-synucleinopathies. Moreover, the findings highlight BDNF as a potential therapeutic target and a candidate adjunct biomarker for diagnosis, monitoring disease activity, or treatment response. Additional experiments will clarify this causal relationship and the utility of BDNF-based interventions in modifying the disease trajectories in DLB and MSA. Show less

Brain-derived neurotrophic factor (BDNF) is a protein crucial to the survival, growth, and differentiation of neurons in the brain and spinal cord. BDNF is monitored across many populations as an indicator of one's cardiometabolic disease (CMD) and mental health (MH) risk. Adults living with a traumatic spinal cord injury (tSCI) are at a higher risk of developing CMD and MH issues, with symptoms often going unrecognized. Establishing serum BDNF as a screening tool within the tSCI population has the potential to improve CMD and MH symptom recognition. This systematic review aims to: (1) explore the tSCI literature to determine whether an association exists between serum BDNF, MH, and CMD risk(s); and; (2) identify best-practice BDNF sampling techniques within the tSCI population. A comprehensive search strategy was developed in collaboration with a University Health Network Librarian. Six databases (MEDLINE, Embase, CENTRAL, APA PsycInfo, CINAHL Ultimate, and Web of Science Core Collection) were searched to identify English-language studies published from inception to July 2025. Studies which reported serum BDNF in the tSCI population in addition to either MH or CMD and have three or more human participants with acute or chronic tSCI were included. Duplicate abstracts were removed and the remaining titles and abstracts reviewed and selected for full-text screening. Study quality was assessed for potential risk of bias using Downs and Black Checklist (Clinical Trials), Newcastle-Ottawa Score (Case-Control Study), or Joanna Briggs Institute Checklist (Cross-sectional Study), prior to data extraction. The serum BDNF analytic methods were reviewed in detail. A total of 2,148 potential studies were identified via the searches, of which 631 duplicates were removed, 1,488 abstracts were excluded for inappropriate population, outcome measure, or study design, and 29 articles were selected for full-text screening, with four studies included in the final review. All studies sampled and analyzed serum BDNF. A total of 271 participants (AIS: A-D, NLI: C1-L5), predominantly male (n = 224), with acute (n = 165) and chronic (n = 51) injuries aged 14-75 as well as healthy controls (n = 55) were included. One study investigated the influence of an intervention and three studies were cross-sectional. No identified study included a description or indication of the prevalence for MH conditions or CMD risk factors. Based on the reviewed literature, links between serum BDNF and MH disorders or CMD risk have not yet been established for individuals with acute or chronic tSCI. The selected studies demonstrated no consistent sampling or analysis methods, with limited adherence to prior established standards in the general population, bringing into question the reliability, validity, and quality of the available outcome data. Show less

A vital question in neuroscience is whether and how efficiently cellular models may be differentiated into functional neuronal cells in culture. Despite the frequent use of the human neuroblastoma cell line SH-SY5Y, differentiation protocols vary extensively, with the most common being differentiation via the addition of retinoic acid and brain-derived neurotrophic factor. However, due to the lack of a reliable evaluation method, their adequacy as synaptic models remains unclear. Here, we investigate whether SH-SY5Y cells constitute a functional model for synaptic studies by phenotypically and ultrastructurally analyzing synaptogenesis in SH-SY5Y cells subjected to different differentiation protocols. Electron microscopy (EM) techniques, including conventional EM, cryo-EM, and cryo-electron tomography, were systematically applied to characterize synaptogenesis in SH-SY5Y cells. Further characterization was performed using immunostaining and functional assays, such as live exocytosis assays and whole-cell patch-clamp electrophysiology. Despite exhibiting some presynaptic-like features, differentiated SH-SY5Y cells do not form morphologically or functionally complete synapses under the conditions tested. Immunostaining results were consistent with previous findings, showing synaptic markers. However, functional investigations did not detect synaptic activity. High-throughput EM analyses revealed an absence of synaptic structures in these cells. Additionally, an alternative differentiation approach incorporating additional neurotrophic factors promoted the formation of presynaptic-like compartments containing synaptic vesicle-like vesicles (SVLVs). In contrast to typical synaptic vesicles, these SVLVs exhibited a pleomorphic size distribution and lacked connectors. These findings underscore the need for cautious interpretation of results derived from SH-SY5Y cells when investigating molecular synaptic architecture or function, as well as neurodegenerative diseases. Show less

Physical exercise and nutritional strategies have become powerful tools for improving brain health, boosting cognitive performance, slowing cognitive decline, and reducing the risk of neurodegenerative diseases, primarily by influencing neurotrophic factors such as brain-derived neurotrophic factor (BDNF). This review examines the impact of various exercise types (endurance, high-intensity interval training, and resistance) along with dietary approaches (ketogenic diet and intermittent fasting) on BDNF, with a focus on their potential to promote cognition and neuroprotective benefits, particularly in the middle-aged and older population. Several molecular and physiological pathways may be involved, including activation of the PGC-1α-FNDC5-BDNF pathway, lactate signaling, increased blood flow to the brain and body, splenic platelet release, and stimulation of TrkB, IGF-1, irisin, and cathepsin B. Nutritional interventions may also boost BDNF through mechanisms involving β-HB and Notch 1 signaling. Research from both animal and human studies highlights the potential benefits of exercise and dietary modifications in supporting brain health and cognitive function. However, differences in study design and methodological limitations make it difficult to draw firm conclusions. These effects appear to be influenced by factors such as exercise characteristics (intensity, modality, and duration), the timing of blood collection, and the type of cognitive assessments. Future studies should focus on identifying the most effective intervention protocols and mechanisms, as well as understanding the individual factors that influence responsiveness to neurotrophic changes. Overall, targeted exercise and dietary strategies offer a promising approach to maintain brain health and reduce cognitive decline associated with aging and disease. Show less

The prevalence of neurodegenerative disorders continues to increase with population aging. Brain-derived neurotrophic factor is a biomarker of cognitive function and neuroprotection. Lactobacillus plantarum C29-fermented soybean (DW2009) has been suggested to enhance cognition by modulating brain-derived neurotrophic factor. This secondary analysis of a randomized, double-blind, placebo-controlled trial investigated the influence of sociodemographic and lifestyle factors on serum brain-derived neurotrophic factor responsiveness to DW2009 supplementation. One hundred adults (age: 55-85 years) with mild cognitive impairment were randomized 1:1 to receive DW2009 (800 mg/day) or placebo (800 mg/day) for 12 weeks. The participants were examined, and their cognitive clinical features and serum brain-derived neurotrophic factor (BDNF) levels were measured at baseline and after a 12-week period. We found that DW2009 significantly increased serum BDNF levels, especially in older men (≥ 68 years) and in those with lower educational attainment (≤ 11 years). Subgroup analysis also indicated that the effect of DW2009 was enhanced in participants who performed frequent physical activity (≥ 5 times/week) and those within the normal body mass index range (18.5-22.9 kg/m²). Our findings suggest that the increase in serum BDNF after DW2009 supplementation is dependent on baseline characteristics, although this interpretation requires confirmation. DW2009 intake was linked to increased serum BDNF levels in individuals with specific sociodemographic and lifestyle characteristics. These findings suggest that personalized supplementation strategies may optimize functional benefits for cognitive health. Show less

Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuronal development, synaptic plasticity, and cognitive function, and its dysregulation is implicated in various neurodegenerative and neuropsychiatric disorders. To noninvasively monitor dynamic changes in Bdnf expression in vivo, we developed a novel transgenic mouse line, Bdnf-AkaLuc transgenic (Tg) mice, in which the coding region of BDNF was replaced in a BAC transgene with a mutant luciferase, AkaLuc. This luciferase is optimized for the synthetic substrate AkaLumine, which emits near-infrared bioluminescence suitable for deep-tissue imaging. This engineered bioluminescence imaging (BLI) system, termed AkaBLI, enables robust and highly sensitive detection of bioluminescence in the brains of living mice, significantly outperforming our previous Bdnf-Luciferase Tg model. Using this system, we successfully visualized activity-dependent Bdnf mRNA induction in response to pilocarpine-induced status epilepticus. To overcome the limitations of repeated imaging, we identified optimal BLI intervals and established a hairless Bdnf-AkaLuc Tg line, facilitating long-term longitudinal monitoring. Furthermore, by crossing Bdnf-AkaLuc Tg mice with 5xFAD Alzheimer's disease model mice, we successfully visualized reductions in Bdnf expression in the brains of living 5xFAD mice. Our study introduces a powerful tool for noninvasive, continuous visualization of Bdnf regulation under both physiological and disease-related conditions. This imaging approach holds potential for advancing our understanding of BDNF-related brain function and for evaluating therapeutic strategies targeting BDNF in neurological disorders. Show less

Myokines and cytokines are signaling proteins released by skeletal muscle cells during exercise that act as messengers, influencing the function of various organs, including the brain. We examined whether a single bout of walking exercise induces distinct changes in plasma myokine and cytokine concentrations in older adults with and without mild cognitive impairment (MCI). In 146 older adults characterized based on the Montreal Cognitive Assessment (MoCA) scores in non-MCI (MoCA score ≥26, n = 55) vs MCI (MoCA score <26, n = 91), we measured cognitive performance by battery, body composition by DXA, and functional performance by 6 min walk test (6MWT) distance. In addition, plasma myokine and cytokine concentrations were assessed before and immediately after 6MWT by MILLIPLEX® Human Myokine Magnetic Bead Panel (HMYOMAG-56K) and Immunology Multiplex Assay (HCYTA-60K-PXBK38) using Luminex® 200™ and MagPix system. Analysis was performed by GLMM to test the effects of group (Non-MCI vs MCI) and walking exercise. The MCI group had worse cognitive performance on trail-making test, stroop color word test (SCWT), phonemic and semantic fluency test, digit span backward, and the Rey auditory verbal learning test (AVLT) delayed memory (all P < 0.02). Body weight, BMI, lean mass, and (visceral) fat mass were comparable between non-MCI and MCI groups. There was a trend toward significantly lower 6MWT distance in the MCI (P = 0.067). We found lower baseline GM-csF concentration (P = 0.006) and a smaller increase in BDNF, FABP-3, and Osteocrin concentration in response to 6MWT in the MCI, even after adjustment for age and 6MWT distance (P < 0.003). Lower BDNF response to exercise was further associated with advancing age and worse cognitive function (MoCA, SCWT) (P < 0.04), but not with changes in lifestyle (habitual physical activity or dietary intake). We observed 6MWT-induced increases for the other myokines (apelin, BDNF, EPO, osteonectin, IL-15, myostatin, FABP-3, FSTL-1, IL-6, FGF-21, and osteocrin), and nearly all cytokines were independent of the group studied (all P < 0.02). A single bout of 6-minute walking exercise elicits a suppressed increase in BDNF, FABP-3, and Osteocrin in individuals with MCI, with a particularly blunted BDNF response in those who are older and more cognitively impaired. Whether disturbances in muscle-brain crosstalk, mediated by suppressed exercise induced BDNF response, contribute to cognitive decline in older adults warrants further investigation. Show less

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric impairments, partly due to disruptions in neurotrophin signaling. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) play critical roles in neuronal survival, synaptic plasticity, and neuroprotection, yet their alterations across biofluids and brain regions in HD remain unclear. This study systematically reviewed and meta-analyzed human and rodent studies to quantify neurotrophin changes and explore moderating factors. Comprehensive searches of PubMed, Scopus, Web of Science, Embase, Google Scholar, and clinical trial registries were conducted up to December 2025. Studies reporting measurable BDNF, NGF, or NT-3 levels in HD patients or animal models were included. Data were extracted on neurotrophin type, sample source, subject characteristics, and measurement methods. Standardized mean differences were calculated using random-effects models, and meta-regression was applied to evaluate the effects of species, sex, sampling region, and analytical techniques. The results showed a significant decrease in neurotrophin levels in both peripheral biofluids and central brain regions in HD. The results for moderator analyses showed that species and sex significantly affected the magnitude of changes in ELISA-based studies, whereas molecular methods consistently detected reductions irrespective of these factors. No significant publication bias was identified. These findings highlight significant neurotrophic deficits in HD, highlight the importance of biological and methodological considerations in interpreting neurotrophin data, and suggest that peripheral neurotrophin measurements may serve as accessible biomarkers for disease progression. Show less

Heart failure (HF) is a complex systemic syndrome with major neuropsychiatric consequences. Cognitive impairment (e.g., dementia) and depression are common among HF patients, worsening prognosis, increasing hospital admissions, and impairing quality of life. Despite their prevalence, the neurobiological basis of these comorbidities is not yet fully understood. This review uniquely discusses converging neuroendocrine, inflammatory, and neuroplastic mechanisms linking HF, depression, and dementia inside an integrative heart-brain axis highlighting brain-derived neurotrophic factor (BDNF) as an important modulator of synaptic plasticity, neurogenesis, and stress resilience. Understanding the interactions between HF-induced hypothalamic-pituitary-adrenal axis activation, systemic inflammation, and impaired BDNF signaling may contribute to the development of novel multimodal therapeutic strategies targeting neurotrophic pathways and improving cognitive and mental health outcomes in HF. Show less

Cognitive flexibility is a core executive function vital for adaptation and adjustment to new information. The brain-derived neurotrophic factor (BDNF) single nucleotide polymorphism, val66met, has been suggested to modulate cognitive flexibility but it remains unclear how confounding variables such as stress and sex influence this relationship. Environmental enrichment (EE) may protect against stress-induced effects. The aim of this study was to test whether BDNF val66met alters reversal learning, a key component of cognitive flexibility, when tested under stressful water maze conditions. We used a Sprague Dawley val66met rat model where pregnant val/met dams were moved to either low or high EE environments. Dams and offspring stayed in these environments until weaning, after which the offspring was moved to standard, moderate enrichment housing. Adult male and female val/val, val/met and met/met offspring then underwent a water maze reversal learning protocol. All groups rapidly learned the new location of the platform. Mediation analysis showed the relationship between val66met and cognitive flexibility was mediated by differential use of spatial strategies. Sequential clustering analysis demonstrated that val66met interacted with sex to predict cognitive flexibility performance with lower flexibility in met/met males and val/met females compared to other genotypes. EE was not a strong promotor of cognitive flexibility. Water maze testing increased corticosterone levels, confirming the stressful nature of the test. This study demonstrates the importance of considering stress and sex when investigating the role of BDNF val66met in cognitive flexibility. Show less

Pacific salmon (Oncorhynchus spp.) rely on olfactory information learned in their natal rivers to guide their homing migration. Although molecules associated with synaptic plasticity show marked changes in the olfactory system during periods linked to imprinting, the contribution of brain-derived neurotrophic factor (BDNF/Bdnf), a key regulator of neural development and plasticity, has not been fully examined in salmonids. In this study, we isolated the complete coding sequence of masu salmon (O. masou) pro-bdnf and analyzed its expression profile across the olfactory system using wild individuals at multiple developmental stages. The deduced amino acid sequence of masu salmon pro-Bdnf was highly conserved among vertebrates. Pro-bdnf mRNA was strongly expressed in under-yearling parr prior to smoltification, particularly in the olfactory rosette and olfactory bulb at the sensitive period for imprinting. In the telencephalon, a higher olfactory center homologous to the mammalian cerebrum, pro-bdnf expression remained stable across stages, consistent with ongoing neurogenesis in this region. These results provide molecular evidence that pro-bdnf expression mirrors developmental changes in the olfactory system and support the idea that Bdnf contributes to the formation and refinement of olfactory circuits essential for imprinting and homing in Pacific salmon. Show less

Recent evidence suggests that reduced peripheral levels of brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of bipolar disorder (BD), although its relevance in young populations remains uncertain. This systematic review synthesized studies that evaluated serum BDNF levels in children and adolescents with BD, examining its potential as a risk marker. Following PRISMA 2020 guidelines and a protocol registered in PROSPERO, searches were conducted in the Cochrane, MEDLINE, SciELO, and Scopus databases. Studies including participants aged 0-19 years diagnosed with BD according to DSM criteria were included. Studies with mixed samples (adults, children and adolescents) without separate age-group analyses were excluded. After screening and eligibility assessment, seven studies were included. Five of them included a control group, from which a meta-analysis was performed. Moderate methodological heterogeneity was observed and corrected after sensitivity analysis, reinforcing the robustness of the findings, although no statistically significant difference in serum BDNF levels was found between patients with bipolar disorder and controls. Current evidence does not support BDNF as a diagnostic biomarker for pediatric BD. Future studies with greater sample power and methodological standardization are needed to clarify its role in the risk and course of early-onset bipolar disorder. Show less

Psychedelic compounds such as psilocybin, Lysergic Acid Diethylamide (LSD), N,Ndimethyltryptamine (DMT), and 3,4-methylenedioxymethamphetamine (MDMA) are emerging as novel therapeutics for neuropsychiatric disorders, including depression, Post-Traumatic Stress Disorder (PTSD), and addiction. Acting primarily through serotonin 5-HT2A receptor agonism, they activate intracellular cascades involving Brain-Derived Neurotrophic Factor (BDNF), Tropomyosin receptor kinase B (TrkB), and the mammalian target of rapamycin (mTOR) pathway, leading to enhanced neuroplasticity and synaptogenesis. Recent evidence demonstrates direct TrkB binding and sustained cortical remodeling, underlying their rapid and durable antidepressant effects. Advanced Drug Delivery Systems (DDS)-including liposomes, Solid Lipid Nanoparticles (SLNs), and Poly(lactic-co-glycolic acid) (PLGA) carriers-are being engineered to achieve controlled, braintargeted, and stimuli-responsive release while minimizing systemic toxicity. Integration with microfluidic fabrication, Artificial Intelligence (AI)-based dosing, and non-invasive routes such as intranasal and transdermal delivery improves precision and patient adherence. By merging neuropharmacology with materials science, these innovations are redefining psychedelic-assisted therapy through enhanced safety, personalized dosing, and translational potential for central nervous system disorders. Show less

Major depressive disorder (MDD) is a leading global health concern. Personalized medicine could enable a better response to antidepressants. Findings suggested optimal response genotypes of Val66Met genetic polymorphism of brain-derived neurotrophic factor (BDNF) (rs6265) in Caucasian depressed patients: selective serotonin reuptake inhibitors (SSRIs) associated with better clinical improvement in Val/Val homozygotes and selective norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAs) with better clinical improvement in Met-allele carriers. We aim to replicate these findings with a meta-analysis. A systematic search of PubMed was performed. All included studies assessed the efficacy of one antidepressant class (SSRIs, SNRIs, or TCAs) in Caucasian patients with a major depressive episode (MDE) in the context of MDD according to BDNF Val66Met genotypes. The primary outcome was remission (MADRS ≤ 12 or HAMD ≤ 7); secondary outcomes were changes from baseline HAMD or MADRS scores and response (≥ 50% reduction). Seven studies were included. In total, 599 patients (357 Val/Val homozygotes and 242 Met-allele carriers) were analyzed. No significant association between optimal response genotypes and remission (190 (56.4%) in the optimal and 146 (54.3%) in the non-optimal genotype response group; fixed effects model: RR = 1.02, 95% CI [0.89; 1.18], p = 0.78) was observed. Similar results were observed for score changes and response. Sensitivity analyses confirmed these findings. Statistical power for primary outcome was 95%. We showed no significant association between the expected optimal response genotype of the BDNF Val66Met polymorphism and clinical improvement after antidepressant treatment in Caucasian depressed patients. Show less

This study investigated the expression of brain-derived neurotrophic factor (BDNF) signaling components (BDNF-TrkB-AKT1) and apoptosis-related factors (Bcl-2 and Bax) in yak brain regions at different altitudes. The cerebral cortex, cerebellum, hippocampus, thalamus, and medulla oblongata were collected from 3-year-old yaks living at low and high altitudes. The relative mRNA expression of BDNF, TrkB, AKT1, Bcl-2, and Bax was assessed by qRT-PCR. Protein abundance and cellular localization of BDNF, TrkB, AKT1, Bcl-2, and Bax were evaluated by Western blotting and immunohistochemistry, with immunoreactivity quantified by optical density analysis. Within each altitude group, BDNF, TrkB, AKT1, and Bcl-2 mRNA expression and the corresponding protein levels (BDNF, TrkB, AKT1, and Bcl-2) were significantly higher in the cerebral cortex and hippocampus than in the cerebellum, thalamus, and medulla oblongata (P < 0.05). In contrast, Bax mRNA and Bax protein levels did not differ significantly among the five regions. Compared with low-altitude yaks, high-altitude yaks showed significantly higher BDNF, TrkB, AKT1, and Bcl-2 mRNA expression and higher BDNF, TrkB, AKT1, and Bcl-2 protein levels in brain tissues (P < 0.05), whereas Bax protein expression did not differ between altitude groups. Immunohistochemistry revealed immunoreactivity for BDNF, TrkB, AKT1, Bcl-2, and Bax in both altitude groups, with prominent labeling in cortical pyramidal neurons and across the pyramidal cell layer in the hippocampal CA region. Immunoreactivity was also detected in large neurons of the thalamus and medulla oblongata. In the cerebellum, labeling was strongest in Purkinje cells, with weaker signals in the granule cell layer and molecular layer. BDNF-TrkB-AKT1 pathway components and Bcl-2 showed relatively higher expression in the cerebral cortex and hippocampus within each altitude group, whereas Bax expression did not vary across regions. These patterns are consistent with an association between BDNF-TrkB-AKT1 signaling and increased Bcl-2 expression without a corresponding increase in Bax, which may support neuronal adaptation in the cerebral cortex and hippocampus. Elevated expression of BDNF, TrkB, AKT1, and Bcl-2 at high altitude suggests enhanced adaptation to hypoxia in high-altitude yaks; the underlying mechanisms require further investigation. Show less

Age-related Macular Degeneration (AMD) is a leading cause of vision loss. There is no cure for AMD. Current treatments focus on preventing disease progression and preserving vision. In recent years, the role of brain-derived neurotrophic factor (BDNF) in AMD has attracted increasing attention. BDNF is widely involved in the physiology and pathophysiology of the retina. These include the development of photoreceptors during early development and synaptic communication between photoreceptors and retinal neurons. Under pathological conditions, BDNF affects the functions of multiple cell types in the retina including photoreceptors, ganglion cells, Müller cells, microglia cells, amacrine cells, and the retinal pigment epithelium (RPE). Importantly, BDNF does not act alone. Its function relates with other neurotrophic factors such as basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), and glial cell derived neurotrophic factor (GDNF). Meanwhile, the dynamic interaction between BDNF, its precursor protein proBDNF and the BDNF receptor TrkB not only affects the survival of retinal cells in AMD but may also guide the treatment strategy. Various approaches have been taken to deliver BDNF in animal models for managing AMD. Despite the exciting progress, challenges remain in implementing BDNF therapy as an effective treatment. In this review, we summarize the current research progress of BDNF in AMD and highlight the issues that need to be addressed before translation into clinical practice. Show less

Childhood growth-restriction can lead to lasting developmental changes, increasing susceptibility to chronic diseases and neurodegenerative conditions in adulthood. High-intensity interval training (HIIT) elevates brain-derived neurotrophic factor (Bdnf) levels more effectively than moderate intensity continuous exercise, supporting neuroplasticity. Building on these findings, this study aimed to determine whether HIIT could enhance neuroplasticity-related protein expression in the brains of PNGR mice. FVB mouse pups born to normal-protein and low-protein-fed dams were cross-fostered at postnatal day (PN) 1 to establish two groups: postnatally growth-restricted mice (PNGR) and control mice (CON). At PN 21, all pups were weaned onto a normal protein diet and assigned to either a high-intensity interval training group (TRD) or a sedentary group (SED). At PN 45, a maximal exercise performance test was conducted to determine HIIT intensities. Based on these results, mice performed treadmill HIIT 5 days per week for 4 weeks, with alternating intervals of 8 minutes at 85% and 2 minutes at 50% of maximal exercise capacity, totaling 60 minutes per session. At PN 73, all mice were euthanized, and cerebrum tissue was collected for western blot analysis of Bdnf, Tropomyosin receptor kinase B (TrkB), Growth-associated protein 43 (Gap-43), and synaptophysin protein expression. Despite significant body mass reductions observed in both CON and PNGR groups following HIIT, neuroplasticity-related protein expression did not increase in PNGR mice. The PNGR group exhibited consistently lower TrkB and reduced Bdnf and Gap-43 levels compared to CON mice, indicating a limited neuroplastic response to exercise. Contrary to expectations, HIIT did not elevate neuroplasticity markers in PNGR mice, highlighting the lasting impact of early-life growth restriction on brain plasticity and suggesting the need for alternative interventions. Show less

Brain-derived neurotrophic factor (BDNF) is a key neurotrophin due to its role in neuron process outgrowth, plasticity, and neuronal survival. Aerobic exercise can induce BDNF release and may ultimately maximize post-stroke recovery. This study aimed to determine if a program of moderate-to-high-intensity aerobic exercise increased concentrations of BDNF in subacute stroke survivors compared to usual care. A parallel-group, RCT was undertaken in people with subacute stroke undergoing rehabilitation. Participants were randomly allocated to usual care (control group) or usual care plus an 8-week program of moderate-high intensity treadmill walking (3 x 30 min sessions per week) (experimental group). Serum BDNF was collected by blinded assessors at baseline (Week 0), at the end of the intervention period (Week 8), and at 6 months follow up (Week 26). Sixty-seven participants ( As concentrations of BDNF increased immediately after a program of aerobic exercise, this may present a potential neurobiological mechanism to enhance recovery after stroke. Show less

The accumulation of CAG nucleotide duplicates in the huntingtin (HTT) gene triggers a neurological ailment described as Huntington's disease (HD), which is an irreversible, progressive, and inherited condition and affects both motor and cognitive abilities, resulting in a range of symptoms, including irregular gestures (chorea, dyskinesia), psychological disorders, and advanced dementia. Agomelatine is a novel antidepressant and melatonin analog. It exerts a synergistic pharmacological mechanism, combining stimulation of both MT1/MT2 melatonergic receptors with inhibition of 5-HT2C receptors. It was evaluated for its potential neuroprotective impact against HD triggered by 3-nitropropionic acid (3-NP) in rats. Four groups were established using a total of 40 rats: Group I (CTRL), Group II (AGO), Group III (3-NP), and Group IV (AGO + 3-NP). Deficits in motor function provoked by 3-NP were alleviated by agomelatine, as evidenced by increased ambulation and rearing frequencies, alongside a notable decline in immobility time of the open field assessment, elevated final falloff time of the rotarod assessment, and improved grip strength. Agomelatine also improved synaptic plasticity and neuronal survival by optimizing the expression and activity of the BDNF/TrKB/PI3K/AKT pathway and inhibiting apoptosis, microglial, and astrocytic activation. Furthermore, agomelatine administration reduced the expression of ROCK1, suppressing the release of inflammatory responses. Finally, agomelatine possessed neuroprotective activity, as proved by enhancing motor activity and histopathological abnormalities via improving the BDNF/TrKB/PI3K/AKT survival cascade and suppressing the ROCK1 inflammatory pathway. Show less

Brain-derived neurotrophic factor (BDNF) plays a role in neuroplasticity, appetite regulation, and reward processing. Its possible involvement in eating disorders (EDs) has been investigated; however, contradictory findings and substantial methodological heterogeneity have prevented definitive conclusions. To systematically evaluate peripheral BDNF levels in individuals with EDs, healthy controls and recovered individuals. A systematic review with meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (CRD420250654199). Observational studies and randomized controlled trials comparing BDNF levels in individuals with and without EDs were included. The Newcastle-Ottawa Scale and risk-of-bias tool for randomized trials were used. Twenty-one studies were included. BDNF serum levels were significantly lower in acute anorexia (AN) compared with healthy controls (Standardized Mean Difference [SMD] = -0.49;p < 0.001,n = 17), with significance maintained after excluding outliers (SMD = -0.41; p < 0.001,n = 8). No significant difference was found between recovered AN and controls. Bulimia nervosa (BN) individuals showed significantly lower BDNF serum levels (SMD = -0.72;p < 0.001,n = 4). Longitudinal studies showed a significant increase in serum BDNF levels after recovery (SMD = 1.78;p = 0.003,n = 6). These findings support a predominantly state-related association between peripheral BDNF levels and illness stage in AN and BN, rather than a stable condition-specific. Evidence for binge-eating disorders is extremely limited, relying on a single eligible study. Interpretation is constrained by methodological heterogeneity, variability in recovery definitions, and the largely correlational nature of the evidence. Further standardized, high-quality longitudinal studies are needed to clarify whether peripheral BDNF alterations reflect state-related mechanisms, trait vulnerability, or dynamic biological changes across illness stages. Show less

Electroconvulsive therapy (ECT) proves to be an effective intervention in severe cases of major depressive disorder (MDD), especially when there is resistance to pharmacological treatment. The neurotrophic hypothesis proposes that an increase in brain-derived neurotrophic factor (BDNF) is one of the mechanisms responsible for the therapeutic response. The aim of this study is to investigate the effects of ECT on peripheral levels of BDNF, measured in serum and plasma, and analyze clinical outcomes associated with this intervention, as well as identify methodological variables that may influence findings. A systematic review and meta-analysis of studies published between 1995 and 2025 on the PubMed, Scopus and Web of Science databases were conducted, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Studies of BDNF in serum (14) and plasma (6) were performed separately. Clinical effectiveness was evaluated according to average standardized differences in depression scores. Meta-regressions in the R software identified the impact of four moderators: type of ECT, number of sessions, type of anesthetic and the time blood sample was taken. ECT was associated with an increase in BDNF levels in both biological matrices, especially in studies with plasma (I Show less

Hypertension is a global target for noncommunicable diseases, and meditation-based interventions (MBIs) benefit patients with hypertension (HTN). The primary objective of this scoping review is to map the globally published MBI studies on patients with HTN. The secondary goal is to identify the role of brain-derived neurotrophic factor (BDNF) in HTN. Based on the Arksey and O'Malley protocol of the Joanna Briggs Institute framework for scoping review, 5 electronic databases were searched with search terms related to HTN and meditation. The open-access articles in the English language published between 1985 and 2024 were selected. The selected articles involved MBIs. All the studies were uploaded to the Rayyan software. Two reviewers worked independently and in duplicate to screen the studies first for title and abstract, and then for full text. Data were extracted based on the template for the intervention description and replication checklist. The data were summarized and reported as a narrative summary. In total, 966 studies were identified. After removing 429 duplicates, 537 studies were screened for their titles and abstracts. 467 studies were excluded based on the inclusion and exclusion criteria, 18 were not retrieved, and 20 were excluded with reasons. Finally, the full texts of 70 studies were read. 32 eligible studies were included in this review. The studies were divided into 3 categories based on meditation and into 7 categories based on outcome. Moreover, no study involving human subjects has analyzed the level of BDNF in HTN patients receiving MBIs. MBIs have shown promising results among HTN patients. There is a research gap in studies related to BDNF and meditation among hypertensive patients. The limitation of the review is the inclusion of open-access articles published only in the English language. Hypertension, Meditation, Mindfulness, Brain-Derived Neurotrophic Factor. Show less

The study aimed to investigate whether involvement in a stable romantic partnership is associated with differences in peripheral brain-derived neurotrophic factor (BDNF) levels. In a cross-sectional study, 60 healthy adults (32 women; mean age 27.4 ± 4.1 years) were classified as in a stable relationship ( Participants in a relationship showed higher PLT-BDNF (4.36 ± 1.22 vs 2.85 ± 0.67 ng/mg; t(58) = 5.90, Our results would indicate that a stable romantic partnership is associated with higher intraplatelet and serum BDNF levels. These findings support an association between current committed romantic relationship status and peripheral BDNF measures in healthy adults. Show less

BackgroundCognitive decline represents a major challenge in aging populations. Probiotics have been proposed to influence cognitive function through gut-brain interactions, but clinical findings remain inconsistent.ObjectiveThis study evaluated the effects of probiotic supplementation on cognitive function as the primary outcome, and on BDNF levels, inflammatory markers, and oxidative stress biomarkers as secondary outcomes in adults aged 50 years and older.MethodsA systematic search of PubMed, EBSCO, ProQuest, and Google Scholar was conducted through 1 May 2024 using predefined search terms related to probiotics, cognitive function, BDNF, inflammation, and antioxidant activity. Study quality was assessed using the RoB 2 tool. Meta-analyses were performed using random-effects models, and publication bias was explored using Egger's test where study counts permitted.ResultsSixteen studies demonstrated significant improvement in cognitive function among participants receiving probiotics compared to placebo. Cognitive function, measured using the Mini-Mental State Examination (MMSE), yielded a standardized mean difference (SMD) of 0.747 (95% CI 0.307-1.186) which corresponds to moderate-to-large effects. In comparison, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) showed significant results with an SMD of 0.340 (95% CI 0.032-1.366) which corresponds to small-to-moderate effects. Probiotics also led to significant changes in several biochemical parameters, including BDNF, TNF-α, 8-OHdG, IL-6, IL-10, MDA, TAC, and GSH. Multi-strain probiotics showed better results compared to single-strain.ConclusionsProbiotic supplementation may offer modest cognitive benefits in aging populations, particularly in studies enrolling cognitively impaired individuals, but substantial heterogeneity and limited biomarker evidence restrict the certainty of these findings. Larger, longer-duration, and standardized trials are needed to clarify the clinical relevance and potential biological pathways underlying probiotic effects on cognition. Show less

Numerous hypotheses have been proposed for the pathophysiology of bipolar disorder (BD). This study aimed to evaluate serum neuroserpin (NSP), tissue plasminogen activator (tPA), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), high-sensitivity C-reactive protein (hsCRP), and sedimentation levels in patients with BD, based on the inflammatory and fibrinolytic system hypothesis, to understand the etiopathogenesis of BD. The second aim of our study was to determine the risk of developing BD type 1 by examining the relationship between tPA and NSP in patients diagnosed with BD type 1. The study included 80 euthymic outpatients with BD type 1 and 80 healthy controls (HC). Individuals with a Hamilton Depression Rating Scale (HAM-D) score of less than 7 and a Young Mania Rating Scale (YMRS) score of less than 4 who did not show any symptoms of mania, depression, or hypomania for the last 6 months were included in the study. In both groups, serum levels of NSP, tPA, IL-6, BDNF, hsCRP, and sedimentation were measured. Compared to the healthy control group, the NSP and tPA levels were lower in the BD group (p<0.001). We found no linear relationship when we analyzed the relationship between tPA and NSP by excluding other variables. (p: 0.027). These findings suggest that tPA and NSP may serve as potential biomarkers for the euthymic period of BD type 1. These biomarkers may provide guidance in understanding the pathophysiology of bipolar disorder. Show less

ObjectiveTo evaluate the effects of a combined psychological and functional exercise intervention on emotion, quality of life, and brain-derived neurotrophic factor (BDNF) levels in patients with Parkinson's disease (PD).MethodsIn this randomized controlled trial, 172 patients with PD were randomly assigned into 2 groups with 86 patients in each group. The control group received routine care, while the intervention group received a 12-week intervention combining psychological support with functional exercise in addition to routine care. Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Parkinson's Disease Questionnaire-39 (PDQ-39), Barthel Index, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and serum BDNF levels were assessed before and after the intervention. Adherence rates were also determined for each group. Spearman correlation analysis was used to examine associations between changes in BDNF (ΔBDNF) and changes in HAMA (ΔHAMA) and HAMD (ΔHAMD) scores.ResultsAt the end of the 12-week clinical trial, the intervention group demonstrated significantly lower HAMA, HAMD, PDQ-39, and MDS-UPDRS scores ( Show less