📚 Article Archive

HSN G1 demonstrates multifaceted therapeutic strategy against Alzheimer disease in APP PS1 mouse model.

Jeong Won Ahn, Eun-Jung Yoon, Hyun Soo Kim +6 more · 2026 · Scientific reports · Nature · added 2026-04-24

Jeong Won Ahn, Eun-Jung Yoon, Hyun Soo Kim, Yunseo Choi, Jiwon Jeong, Kongara Damodar, Yeong-Min Yoo, Dongsun Park, Seong Soo Joo Show less

Current therapeutic approaches for Alzheimer's disease (AD) demonstrate limited efficacy and fail to address disease progression. In the present study, we present HSN-G1, a novel ginsenoside-enriched Show more

Current therapeutic approaches for Alzheimer's disease (AD) demonstrate limited efficacy and fail to address disease progression. In the present study, we present HSN-G1, a novel ginsenoside-enriched pharmaceutical formulation that employs a dual-target mechanism through the modulation of amyloid clearance pathways and cholinergic neurotransmission. HSN-G1 demonstrates a reproducible ginsenoside profile enriched with Re (33.27 mg/g), Rd (25.00 mg/g), and Rg3 stereoisomers (12.18 mg/g), ensuring pharmaceutical-grade reproducibility. HSN-G1 enhanced amyloid-beta (Aβ) clearance in microglial cells, with significantly greater effects observed in SRA-overexpressing cells, suggesting SRA-dependent clearance mechanisms. In APP/PS1 transgenic mice, six-week oral administration of HSN-G1 (100-400 mg/kg) elicited significant dose-dependent improvements in cognitive performance. Male mice exhibited more stable and consistent enhancements in both passive avoidance and spatial memory tests compared to vehicle controls (p < 0.001), while both sexes demonstrated comparable reductions in brain Aβ levels (approximately 45%) and differential increases in acetylcholine (73% in males; 55% in females, p < 0.01). HSN-G1 administration enhanced the expression of neurotrophic factors, with NGF upregulation predominantly observed in males, whereas BDNF, CNTF, and GDNF were consistently elevated across both sexes. These findings establish HSN-G1 as a promising disease-modifying agent with standardized composition and therapeutic efficacy, surpassing the limitations of conventional single-target approaches. The superior efficacy of HSN-G1 compared to existing treatments validates its potential for clinical development, highlighting the significance of sex-specific therapeutic responses in future AD therapeutics. Show less

📄 PDF DOI: 10.1038/s41598-026-49541-9

BDNF alzheimer alzheimer disease amyloid amyloid clearance animal study bdnf/trkb biomarker

Transcranial vibrotactile stimulation enhances hippocampal cholinergic signaling and memory through frequency-dependent mechanotransduction.

Ok-Hyeon Kim, Chang-Ho Shin, Min-Woo Cho +7 more · 2026 · Scientific reports · Nature · added 2026-04-24

Ok-Hyeon Kim, Chang-Ho Shin, Min-Woo Cho, Jae-Young Ha, Jai Jun Choung, Dong-Keun Song, Jae-Yeong Choi, Eun Seo Chang, Hyun Jung Lee, Sae-Kwang Ku Show less

Cholinergic dysfunction is a key contributor to cognitive impairment observed in aging and neurodegenerative disorders such as Alzheimer's disease (AD). Although acetylcholinesterase (AChE) inhibitors Show more

Cholinergic dysfunction is a key contributor to cognitive impairment observed in aging and neurodegenerative disorders such as Alzheimer's disease (AD). Although acetylcholinesterase (AChE) inhibitors have been the mainstay of symptomatic treatment for over two decades, their limited efficacy and adverse effects underscore the need for alternative therapeutic approaches. Recent evidence indicates that mechanical stimulation can modulate neuronal and glial signaling through mechanotransduction, suggesting a potential strategy to enhance cognitive function via non-pharmacological means. Here, we developed a head-mounted vibrotactile stimulation system (HVSS) that delivers controlled vibration to the cranium and evaluated its effects in a pharmacological model of acute cholinergic dysfunction induced by scopolamine. To this end, male C57BL/6 mice received scopolamine (1 mg/kg, i.p.; on days 7, 14, and 28) and were exposed to daily vibrotactile stimulation at 20, 40, or 80 Hz for 28 days. Behavioral performance was assessed using passive avoidance and Morris water maze tests, followed by biochemical and histological analyses. HVSS at 40 Hz and 80 Hz significantly improved cognitive performance, enhanced hippocampal cholinergic function, reduced oxidative damage, and upregulated memory-related signaling genes, including BDNF, PI3K, AKt, ERK1/2, CREB, and CAMK4. These findings suggest that high-frequency HVSS improves memory hippocampal cholinergic function via activation of memory-related signaling pathways, highlighting its potential as a safe, non-pharmacological neuromodulatory strategy for cholinergic dysfunction-related cognitive decline. Show less

📄 PDF DOI: 10.1038/s41598-026-49377-3

BDNF aging alzheimer's disease animal study bdnf/trkb biomarker brain cholinergic signaling

A Network Pharmacology and Bioinformatics Approach for Determining the Mechanisms and Molecular Targets of Catechins Against Epilepsy.

Punam Salaria, Desu Gayathri Niharika, Satyanarayana K Konavarapu +2 more · 2026 · Biotechnology and applied biochemistry · Wiley · added 2026-04-24

Punam Salaria, Desu Gayathri Niharika, Satyanarayana K Konavarapu, Amarendar Reddy M, Sung Yeol Kim Show less

Epilepsy is a debilitating neurological disorder that impacts approximately 50 million people worldwide. The treatment of epilepsy with antiepileptic drugs has not achieved effective seizure managemen Show more

Epilepsy is a debilitating neurological disorder that impacts approximately 50 million people worldwide. The treatment of epilepsy with antiepileptic drugs has not achieved effective seizure management and thus requires new therapeutic options. This study investigated the catechins' affect on epilepsy-related molecular targets using a computational method that combined network pharmacology, molecular docking, and molecular dynamics (MDs) simulation. We fetched 84 catechins-related and 5356 disease-associated targets from various databases, yielding 31 common targets. The protein-protein interaction (PPI) network of 31 common targets identified 10 hub genes, including ALB, INS, brain-derived neurotrophic factor (BDNF), PTGS2, tumor necrosis factor (TNF), IL1B, FOS, IL6, LEP, and FGF2. Further, the functional enrichment analysis revealed that these common targets have a high prevalence in multiple pathways and gene ontology functions. Furthermore, "compound-target" and "compound-gene-pathway" networks were constructed and analyzed. Network pharmacology data show TNF, IL1B, and IL6 could influence epilepsy treatment by regulating several pathways. The Cresset Flare Pro+ docking study unveiled that the lead catechin, epigallocatechin gallate (EGCG), exhibited the highest Lead Finder (LF) dG scores of -10.2, -9.40, and -8.15 kcal/mol against TNF, IL6, and IL1B, respectively. The electrostatic complementarity and Molecular Mechanics with Generalized Born and surface area (MMGBSA) results supported the docking results. Further, the stability of EGCG-bound complexes was analyzed using a 300 ns MD simulation. The principal component analysis yielded promising results for the EGCG-2AZ5 and EGCG-1ALU complexes collective motion. These findings provide computational evidence suggesting that EGCG has a promising scaffold for designing multi-target molecules that could modulate epilepsy, meriting further experimental validation. Show less

no PDF DOI: 10.1002/bab.70176

BDNF bioinformatics epilepsy molecular docking molecular dynamics molecular targets network pharmacology neurological disorder

IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes.

Andrew J Elmendorf, Mostafa Yousefian, Il-Man Kim +3 more · 2026 · Pharmacological research · Elsevier · added 2026-04-24

Andrew J Elmendorf, Mostafa Yousefian, Il-Man Kim, J Andrew Hardaway, Kirk Habegger, Jonathan N Flak Show less

The epidemics of metabolic disease, in the form of obesity and type 2 diabetes, are a growing public health concern. However, incretin-based therapeutics have transformed our ability to address these Show more

The epidemics of metabolic disease, in the form of obesity and type 2 diabetes, are a growing public health concern. However, incretin-based therapeutics have transformed our ability to address these diseases. While this current generation of incretin analogues show weight regain upon cessation of treatment, the amount of which can depend on the treatment and patient, iterative advancements may improve weight loss durability in the long term. In this review, we discuss the development of glucagon like peptide-1 receptor (GLP-1R) agonists and GLP-1R/ glucose-dependent insulinotropic polypeptide receptor (GIPR) co-agonists, and how future generations will leverage this strategy. We focus our review on glucagon receptor (GCGR) agonism, which has recently been combined with both GLP-1R and GLP-1R/GIPR agonism to generate dual (e.g. survodutide, cotatutide, mazdutide, etc) and triple agonists (e.g. retatrutide, etc) for improved body weight loss via energy expenditure stimulation. We rely on largely pre-clinical evidence for action because clinical data is extremely limited for GCGR agonism. Herein, we review mechanisms by which glucagon receptor agonists act to increase energy expenditure. Finally, we discuss future improvements to incretin-based therapeutics, and how they can include strategies that target the GCGR. The purpose of this review is to discuss mechanisms by which GCGR agonism can reduce body weight and put them in the context of the combination with incretin receptor agonists. Mechanistic data has only currently been evaluated in preclinical rodent models and evidence for similar processes in humans is limited. We also provide perspectives about how treatments can improve for future advancement of obesity treatment. Show less

📄 PDF DOI: 10.1016/j.phrs.2025.108077

GIPR

Loss of Tubby in MC4R- and VGLUT2-Expressing Neurons Impairs Energy Homeostasis.

Se Rok Jeong, Yong Taek Jeong, Chul Hoon Kim +2 more · 2026 · BMB reports · added 2026-04-24

Se Rok Jeong, Yong Taek Jeong, Chul Hoon Kim, Jeong Taeg Seo, Seok Jun Moon Show less

Obesity is a major global health crisis, yet the molecular mechanisms underlying adult-onset metabolic dysfunction remain incompletely understood. The tubby mouse is a foundational genetic model of ma Show more

Obesity is a major global health crisis, yet the molecular mechanisms underlying adult-onset metabolic dysfunction remain incompletely understood. The tubby mouse is a foundational genetic model of maturity-onset obesity; however, the specific tissues and cell populations responsible for its metabolic phenotype have long remained elusive. Here, we demonstrate that the loss of tubby disrupts the coordinated regulation of energy intake and expenditure, leading to a sustained positive energy balance. Using cell-type-specific genetic tools, we identified MC4R-expressing and VGLUT2-expressing neurons as essential sites of tubby function. We found that tubby acts through the combined contribution of these neuronal populations, as selective deletion in either MC4R or VGLUT2 neurons is sufficient to phenocopy key features of the global Tub mutant. Together, these findings establish tubby as a central neuronal regulator of systemic energy homeostasis and define an excitatory MC4R-VGLUT2 circuit that governs feeding behavior and metabolic output. Show less

no PDF

MC4R

Maternal Nutrition and Hypothalamic Programming of Offspring Metabolic Health.

Smita Mall, Busayo Oladun, Min-Hyun Kim · 2026 · The Journal of nutrition · Elsevier · added 2026-04-24

The hypothalamus plays a central role in regulating metabolism by integrating hormonal and nutrient-derived signals to maintain energy homeostasis across the life span. Maternal nutritional status dur Show more

The hypothalamus plays a central role in regulating metabolism by integrating hormonal and nutrient-derived signals to maintain energy homeostasis across the life span. Maternal nutritional status during critical windows of development is a major environmental factor that can permanently alter this regulation. Both maternal overnutrition and undernutrition have been shown to disturb circulating leptin, insulin, and glucagon-like peptide-1 (GLP-1), and to disrupt the normal development of hypothalamic nuclei implicated in energy balance. Experimental and clinical studies indicate that these insults miswire proopiomelanocortin (POMC) and neuropeptide Y/agouti-related peptide (NPY/AgRP) pathways, alter leptin and insulin receptor signaling, trigger neuroinflammation, glial and vascular changes, and are accompanied by enduring epigenetic alterations, including DNA methylation and chromatin remodeling at genes such as Pomc, Npy, Mc4r, Lepr, and Insr. Together, these adaptations establish new set points for appetite, energy expenditure, and glucose regulation, thereby increasing the lifelong risk of obesity and type 2 diabetes in the offspring. In this narrative review, we synthesize evidence from animal models and human studies linking maternal nutrition to hypothalamic programming via leptin, insulin, and GLP-1. We also highlight major gaps, including limited data on GLP-1 in maternal undernutrition, the specific role of individual micronutrients, and the timing and reversibility of hypothalamic programming, to inform future mechanistic, translational, and preventive research. Show less

no PDF DOI: 10.1016/j.tjnut.2026.101515

MC4R

Exploring the Association Between DTC Obesity-Related Gene Polymorphisms and Obesity Risk Factors in Koreans: Focus on

Jiha Kim, Soyoun Lee, Myoungsook Lee · 2026 · Nutrients · MDPI · added 2026-04-24

Among more than 300 candidate genes for obesity, A total of 231 healthy adults aged 19-64 years were recruited between March and May 2024. Anthropometric and clinical measurements, genotyping, dietary Show more

Among more than 300 candidate genes for obesity, A total of 231 healthy adults aged 19-64 years were recruited between March and May 2024. Anthropometric and clinical measurements, genotyping, dietary intake, and questionnaires on socioeconomic status, family history, and lifestyle behaviors were obtained. Associations between genotypes and obesity-related phenotypes were evaluated using ANOVA and ANCOVA, multivariable-adjusted models and multicollinearity analysis-based stepwise regression. In Koreans, MAFs for These findings support the relevance of Show less

📄 PDF DOI: 10.3390/nu18040655

MC4R

Petasites japonicus Leaves Alleviate Depression in Dextran Sulfate Sodium-Induced Colitis Mice Through the BDNF/TrkB Pathway and Modulation of Inflammation.

Hwa Rang Na, Hyo Lim Lee, Hye Ji Choi +4 more · 2026 · International journal of molecular sciences · MDPI · added 2026-04-24

Hwa Rang Na, Hyo Lim Lee, Hye Ji Choi, Yu Mi Heo, Yeong Hyeon Ju, Hyun-Jin Kim, Ho Jin Heo Show less

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a high incidence of anxiety and depression. However, the underlying mechanisms of these symptoms remain to be fully elucida Show more

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a high incidence of anxiety and depression. However, the underlying mechanisms of these symptoms remain to be fully elucidated. This study investigated the effects and mechanisms of a 20% ethanolic extract of Show less

📄 PDF DOI: 10.3390/ijms27073274

BDNF

Serpina1e mediates the exercise-induced enhancement of hippocampal memory in male mice.

Hyunyoung Kim, Sanghee Shin, Jeongho Han +3 more · 2026 · Nature communications · Nature · added 2026-04-24

Hyunyoung Kim, Sanghee Shin, Jeongho Han, Kangseok Yun, Jong-Seo Kim, Hyungju Park Show less

Exercise enhances learning and memory, not only through improved cardiometabolic but also through body-brain interactions mediated by secreted factors. Given the prominent role of skeletal muscle duri Show more

Exercise enhances learning and memory, not only through improved cardiometabolic but also through body-brain interactions mediated by secreted factors. Given the prominent role of skeletal muscle during exercise, muscle-derived factors, myokines, are believed to mediate the exercise-induced cognitive enhancements. Here, we demonstrate that intramuscular Serpina1e is upregulated following exercise in male mice. Systemic delivery of recombinant Serpina1e or intramuscular overexpression of Serpina1e reproduces exercise-induced memory enhancements in sedentary male mice. Conversely, muscle-specific depletion of Serpina1e abolishes hippocampal memory enhancement, indicating a requirement of muscle-derived Serpina1e for these cognitive benefits. Mechanistically, elevated plasma Serpina1e stimulates neurogenesis, brain-derived neurotrophic factor (BDNF) expression, and neurite growth in the hippocampus by crossing the blood-cerebrospinal fluid (CSF) and blood-brain barrier. Our findings identify Serpina1e as a key mediator of skeletal muscle-brain interaction that enables the beneficial effects of exercise on cognitive function. Show less

no PDF DOI: 10.1038/s41467-026-71420-0

BDNF cardiometabolic cognitive exercise hippocampal memory myokines skeletal muscle

Therapeutic potential of exerkines in neurodegenerative and mental disorders: a narrative review.

Suwol Yang, Hye-Won Sang, Seoyeon Kim +7 more · 2026 · Frontiers in physiology · Frontiers · added 2026-04-24

Suwol Yang, Hye-Won Sang, Seoyeon Kim, Eun-Jeong Cho, Youngju Choi, Dong Woo Kang, Young C Jang, Dong-Ho Park, Hyo-Bum Kwak, Jang Soo Yook Show less

Neurodegenerative and mental disorders impose significant global disease burdens and pose serious social and economic challenges. Physical exercise (PE) exerts beneficial effects on brain health, cont Show more

Neurodegenerative and mental disorders impose significant global disease burdens and pose serious social and economic challenges. Physical exercise (PE) exerts beneficial effects on brain health, contributing to a reduction in the risk of Alzheimer's disease (AD), Parkinson's disease (PD), depression, anxiety, and post-traumatic stress disorder (PTSD). To understand these effects of PE, a variety of molecules released from various tissues in response to PE have been discovered, which are collectively called 'exerkines'. In particular, the skeletal muscle acts as an endocrine organ, secreting exerkines and is included in the category of myokines that facilitate direct or indirect crosstalk between the muscle and the brain. Although muscles actively interact with organs such as the liver, pancreas, and adipose tissue, the precise mechanisms of muscle-brain communication have yet to be fully elucidated. In the skeletal muscle, the types of exerkines secreted and their effects vary depending on the PE modality. Furthermore, these exerkines can cross the blood-brain barrier (BBB) to exert direct effects or act indirectly Show less

📄 PDF DOI: 10.3389/fphys.2026.1793043

BDNF

Effects of DW2009 on BDNF Levels as a Secondary Analysis of a Randomized Controlled Trial Across Sociodemographic Subgroups.

Min Cheol Kim, Dae Yeon Won, Hyunju Kim +3 more · 2026 · Current Alzheimer research · Bentham Science · added 2026-04-24

Min Cheol Kim, Dae Yeon Won, Hyunju Kim, Jong-Woo Paik, Ah Rah Lee, Yun-Ha Hwang 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 pla Show more

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

no PDF DOI: 10.2174/0115672050457704260126083119

BDNF biomarker brain-derived neurotrophic factor cognitive function lactobacillus plantarum neurodegenerative disorders neuroprotection sociodemographic factors

Signal peptide-directed proteins generated in the endoplasmic reticulum are secreted or degraded via the autophagic pathway.

Taek-Yeong Kim, Ye-Jin Cho, Kwon-Yul Ryu · 2026 · Biochimica et biophysica acta. Molecular cell research · Elsevier · added 2026-04-24

Signal peptides (SPs) are short N-terminal sequences that direct proteins to the endoplasmic reticulum (ER). After cleavage of the SP, these proteins are mostly trafficked to the Golgi apparatus for s Show more

Signal peptides (SPs) are short N-terminal sequences that direct proteins to the endoplasmic reticulum (ER). After cleavage of the SP, these proteins are mostly trafficked to the Golgi apparatus for secretion. Lipocalin-2 (LCN2), a neurotoxic secretory protein, was recently identified as a target of autophagy. The presence of an SP is a prerequisite for secretion and autophagic degradation. Based on these observations, we investigated whether the SP of LCN2 is sufficient to enable proteins to be secreted or degraded via autophagy. We fused the SP of LCN2 to a non-secretory green fluorescent protein (GFP) and found that this ER-generated GFP was either secreted or degraded via autophagy. These results indicate that the LCN2-derived SP alone is sufficient to direct proteins to the ER and subsequent secretion or autophagic degradation. This dual regulation was abolished when the SP was deleted from LCN2. Notably, the effect was preserved even when the LCN2 SP was replaced with the SP from brain-derived neurotrophic factor, another secretory protein. These results suggest that SPs with different sequences can similarly direct proteins to the ER and subsequent secretion or autophagic degradation. Furthermore, we found that even when LCN2 reached the Golgi apparatus for secretion, it could also be degraded via autophagy. Thus, we propose that SP-directed and ER-generated secretory proteins can undergo autophagic degradation during ER-Golgi transport, including at the ER, the ER-Golgi intermediate compartment, or the Golgi apparatus. Taken together, degradation of secretory proteins via autophagy suggests implications for the potential control of secretory protein homeostasis. Show less

no PDF DOI: 10.1016/j.bbamcr.2026.120140

BDNF autophagic pathway autophagy degradation endoplasmic reticulum protein secretion secretory protein signal peptide

Efficacy and Safety of Standardized Ethanol Extract of Purple Perilla (

Hyang-Im Baek, Jong Cheon Joo, Sung-Kyu Kim +4 more · 2026 · Nutrients · MDPI · added 2026-04-24

Hyang-Im Baek, Jong Cheon Joo, Sung-Kyu Kim, Mi-Houn Park, Gun Hee Cho, Lei Shen, Soo Jung Park Show less

📄 PDF DOI: 10.3390/nu18060960

BDNF

Changes in Blood DNA CpG Methylation Levels in Response to Methadone Maintenance Treatment: Epigenome-Wide Longitudinal Study.

Orna Levran, Yuli Kim, Justin Li +3 more · 2026 · Epigenomes · MDPI · added 2026-04-24

Orna Levran, Yuli Kim, Justin Li, Anat Sason, Miriam Adelson, Einat Peles Show less

Methadone maintenance treatment (MMT) is one of the major pharmacotherapies for opioid use disorder. The underlying mechanisms of addiction and the treatment response are only partially understood. Th Show more

Methadone maintenance treatment (MMT) is one of the major pharmacotherapies for opioid use disorder. The underlying mechanisms of addiction and the treatment response are only partially understood. The study's main goal was to identify differential DNA CpG methylation that occurred in response to MMT. Toward this goal, we have conducted a longitudinal epigenome-wide study of blood samples from 64 patients at the beginning and after 1-3 years of MMT, using a linear mixed model. A total of 1881 differentially methylated probes (DMPs) were identified (FDR < 0.05), controlling for sex, age, estimates of blood cell proportions, and the first two principal components based on genome-wide SNP genotypes. Among the genes annotated to the top DMPs are The study provides preliminary insight into the epigenetic effect of MMT. Future studies will have to confirm the DMPs, assess their impact on gene expression, and determine their clinical relevance. Show less

📄 PDF DOI: 10.3390/epigenomes10010018

BDNF

Neuroprotective Effects of Transplanted Induced Pluripotent Stem Cell-Derived Neural Precursors in Huntington's Disease Models.

Hyeonjoong Jeon, Il-Shin Lee, Dong Gyu Lee +6 more · 2026 · International journal of stem cells · added 2026-04-24

Hyeonjoong Jeon, Il-Shin Lee, Dong Gyu Lee, Kyoung Seo Park, Sanghun Lee, Hyo Chang Park, Beomsoo Kim, Hyun Sook Kim, Jihwan Song Show less

Huntington's disease (HD) is characterized by progressive striatal degeneration associated with mutant huntingtin (mHTT)-related proteostatic disruption and chronic neuroinflammation. Although mHTT-lo Show more

Huntington's disease (HD) is characterized by progressive striatal degeneration associated with mutant huntingtin (mHTT)-related proteostatic disruption and chronic neuroinflammation. Although mHTT-lowering approaches hold therapeutic promise, their capacity to restore the degenerating neural microenvironment remains limited. Here, we evaluated the therapeutic potential of human induced pluripotent stem cell (iPSC)-derived neural precursor cells (s513-NPCs) in two complementary HD models, the acute R6/2 transgenic fragment model and the protracted, full-length YAC128 genomic model. Intrastriatal transplantation of s513-NPCs resulted in sustained functional improvement, including stabilization of motor coordination and attenuation of neuromuscular decline, across both disease contexts. These neuroprotective effects were accompanied by efficient donor cell engraftment and integration within the host striatum. At the molecular level, transplantation was associated with coordinated changes in proteostasis-related pathways, reflected by reduced mHTT aggregate burden and modulation of proteasomal and autophagic markers. In parallel, enhanced local BDNF-TrkB signaling was observed in grafted regions, consistent with improved neuronal support. Notably, transplanted NPCs exhibited context-dependent immunological responses, characterized by attenuation of pro-inflammatory signatures in aggressive disease stages and features of a reparative microenvironment in more protracted settings. Collectively, these findings demonstrate that iPSC-derived neural precursor transplantation confers robust neuroprotective effects in HD models, supporting its potential as a stem cell-based strategy to mitigate striatal pathology and functional decline. Show less

no PDF DOI: 10.15283/ijsc26001

BDNF huntington's disease induced pluripotent stem cells neural precursors neurodegeneration neuroinflammation neuroprotection stem cell therapy

Temporal association between NRF2/HO-1 activation, endogenous BDNF up-regulation, and motor recovery in a male mouse MCAO model.

Junghee Park, Hyoin Hwang, Hyekyoung Shin +3 more · 2026 · Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · Elsevier · added 2026-04-24

Junghee Park, Hyoin Hwang, Hyekyoung Shin, Yoonyoung Chung, Dongjoon Kim, Yonghyun Jun Show less

Stroke induces severe neurological impairment, however, there is limited understanding of the mechanisms underlying post-stroke recovery. Nuclear factor erythroid 2-related factor 2 (NRF2) and brain-d Show more

Stroke induces severe neurological impairment, however, there is limited understanding of the mechanisms underlying post-stroke recovery. Nuclear factor erythroid 2-related factor 2 (NRF2) and brain-derived neurotrophic factor (BDNF) have been implicated in tissue responses to ischemic injury; however, their temporal interactions in middle cerebral artery occlusion (MCAO) models are not fully understood. Male C57BL/6 mice (7-8 weeks) were subjected to transient MCAO (tMCAO). Motor behavior, cerebral blood flow, and temporal changes in NRF2, heme oxygenase-1 (HO-1), and BDNF expression were assessed over 14 days. Cerebral blood flow in the ischemic cortex remained significantly reduced for up to 14 days after MCAO. Motor deficits were most severe on day 3 and showed gradual recovery by day 7. NRF2 expression peaked on day 3, whereas HO-1 and BDNF expression increased on days 7 and 14, coinciding with improved motor performance and increased neuronal preservation. These findings indicate that activation of the NRF2/HO-1 pathway is temporally associated with increased expression of endogenous BDNF and recovery of motor function following ischemic injury in male mice. Show less

no PDF DOI: 10.1016/j.jstrokecerebrovasdis.2026.108616

BDNF bdnf ho-1 ischemia mcao neurotrophic factor nrf2 stroke

Therapeutic Assessment of TrkB Agonist in a Unilateral Blast-Induced Hearing Loss Mouse Model.

Sung Kyun Kim, Han-Gyu Bae, Jun Hee Kim · 2026 · Audiology research · MDPI · added 2026-04-24

Blast-induced hearing loss (BIHL) is a major concern, particularly for military personnel, and is linked to impaired auditory neuron survival and synaptic plasticity. This study investigates the poten Show more

Blast-induced hearing loss (BIHL) is a major concern, particularly for military personnel, and is linked to impaired auditory neuron survival and synaptic plasticity. This study investigates the potential of the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) to reduce the severity of BIHL and promote recovery in a mouse model. Eight-week-old male C57BL/6J mice were used. A custom-built, compressed air-driven system utilizing a modified paintball apparatus was employed to deliver controlled unilateral double blasts (~22 psi exposure pressure) to the left ear. The blasts were administered 30 min apart. Immediately following the second blast, mice received either 7,8-DHF (10 mg/kg) or vehicle (10% DMSO) via intraperitoneal injection. Auditory brainstem responses (ABRs) were measured in both ears at baseline (pre-blast) and at several post-exposure time points. The consecutive blast exposure induced a significant elevation in ABR thresholds, indicative of hearing loss, in both the ipsilateral (exposed) and contralateral (unexposed) ears of vehicle-treated mice. Notably, mice treated with 7,8-DHF demonstrated a marked improvement in hearing recovery compared to the vehicle group. Significant reductions in ABR thresholds were observed in the ipsilateral ear at 4 weeks post-blast ( A controlled blast model demonstrates that systemic administration of the TrkB agonist 7,8-DHF exerts a protective effect, partially restoring auditory function after blast injury. This supports the therapeutic potential of targeting the BDNF-TrkB signaling pathway for managing BIHL. Show less

📄 PDF DOI: 10.3390/audiolres16020036

BDNF

Roots of cognitive abnormalities in BTBR male mice: Brain dysmorphology, CSF flow impairment and aberrant BDNF expression.

Anton Tsybko, Tatiana Ilchibaeva, Dmitrii Petrovskii +5 more · 2026 · Progress in neuro-psychopharmacology & biological psychiatry · Elsevier · added 2026-04-24

Anton Tsybko, Tatiana Ilchibaeva, Dmitrii Petrovskii, Elizaveta Silvanovich, Vladimir Kim, Nikita Khotskin, Alexander Romashchenko, Vladimir Naumenko Show less

This study examines neuroanatomical and molecular changes that may be responsible for cognitive impairment in the BTBR mouse model of autism. Compared to control C57Bl/6 mice, BTBR mice exhibited cogn Show more

This study examines neuroanatomical and molecular changes that may be responsible for cognitive impairment in the BTBR mouse model of autism. Compared to control C57Bl/6 mice, BTBR mice exhibited cognitive inflexibility, impaired in an operant learning task. MRI revealed significant brain abnormalities, including reduced cortical volume, smaller ventricles, and asymmetry in the dorsal hippocampus, accompanied by neuronal loss. BTBR mice also showed impaired cerebrospinal fluid dynamics, with reduced production and outflow. Molecular analysis revealed brain region-specific reduction in the expression of Bdnf exons 1, 2, 3, and 4 in untrained BTBR mice. Furthermore, learning induced changes in transcription of Bdnf exons exclusively in BTBR. Elevated proBDNF levels and an increased proBDNF/mature BDNF ratio in the frontal cortex and striatum indicated aberrant BDNF processing. These findings suggest that ASD-related cognitive impairments are linked to a complex of neurodevelopmental abnormalities, potentially connected to disrupted transcription, processing, and signaling of BDNF. Show less

no PDF DOI: 10.1016/j.pnpbp.2026.111656

BDNF autism bdnf brain abnormalities cognitive impairment mri neuroanatomy neuroscience

Serum BDNF levels as a potential prognostic marker for functional recovery in stroke: Preliminary findings from a prospective observational study.

Seyoung Shin, Heegoo Kim, Dae Hyun Kim +1 more · 2026 · PloS one · PLOS · added 2026-04-24

Seyoung Shin, Heegoo Kim, Dae Hyun Kim, Won Hyuk Chang Show less

Brain-derived neurotrophic factor (BDNF) crosses the blood-brain barrier and may serve as a marker of neuroplasticity. This study evaluated whether serum levels of mature BDNF, proBDNF, and matrix met Show more

Brain-derived neurotrophic factor (BDNF) crosses the blood-brain barrier and may serve as a marker of neuroplasticity. This study evaluated whether serum levels of mature BDNF, proBDNF, and matrix metalloproteinase-9 (MMP-9) can predict functional recovery after stroke. In this prospective observational study, 93 patients with unilateral stroke and motor impairment were recruited. Clinical, and demographic data, as well as serum levels of mature BDNF, proBDNF, and MMP-9 were collected. Functional assessments measuring stroke severity, cognition, motor function, balance, and mood were conducted at three timepoints: after acute care (T0), 2 weeks post-rehabilitation (T1), and 3 months post-onset (T2). Mature BDNF significantly decreased from T0 to T2 (p = 0.003), while proBDNF remained stable. MMP-9 declined consistently across timepoints (p < 0.001). MMP-9 levels at baseline differed by BDNF genotype (p < 0.05). However, none of the biomarkers independently predicted functional recovery. Functional outcomes improved significantly over time (p < 0.001), with baseline functional scores being the strongest predictors at T1 and T2. Although these biomarkers were not independent predictors of recovery, their longitudinal trajectories may reflect underlying neurobiological recovery mechanisms during rehabilitation, although their prognostic utility remains inconclusive. Show less

📄 PDF DOI: 10.1371/journal.pone.0343929

BDNF

Environmental Enrichment Attenuates Aging-Induced BBB Disruption and Cognitive Impairment with Activation of FNDC5/Irisin Signaling.

Jae Min Lee, You Jung Choi, Da-Eun Sung +2 more · 2026 · International journal of molecular sciences · MDPI · added 2026-04-24

Jae Min Lee, You Jung Choi, Da-Eun Sung, Seung Geun Yeo, Youn-Jung Kim Show less

Aging disrupts the neurovascular unit (NVU) and blood-brain barrier (BBB), elevates glial inflammatory tone, and compromises hippocampal memory. Environmental enrichment (EE)-a multimodal, lifestyle-b Show more

Aging disrupts the neurovascular unit (NVU) and blood-brain barrier (BBB), elevates glial inflammatory tone, and compromises hippocampal memory. Environmental enrichment (EE)-a multimodal, lifestyle-based intervention-improves cognition, but its association with BBB/NVU and FNDC5/irisin-related signaling in aging remains incompletely understood. Aged male C57BL/6J mice (21 months old) were housed under EE or standard conditions for 11 weeks. Hippocampal-dependent spatial working memory was assessed using the radial eight-arm maze, and neuronal (NeuN), glial (Iba1, GFAP), and BBB/NVU markers (AQP4 endfoot polarity, occludin, ZO-1, PECAM-1, microvessel length/density) were quantified. FNDC5/irisin-related signaling was evaluated by measuring PGC-1α, FNDC5/irisin, IGF-1, BDNF, Show less

📄 PDF DOI: 10.3390/ijms27041652

BDNF

The Effect of High-Intensity Interval Training on Neuroplasticity-Related Proteins in the Cerebrum of Postnatally Growth-Restricted Mice.

Seong-Hyun Kim, Melissa A Quinn, Julian Ananyev +3 more · 2026 · Medicine and science in sports and exercise · added 2026-04-24

Seong-Hyun Kim, Melissa A Quinn, Julian Ananyev, Ashley C Mcpeek, Eric C Leszczynski, David P Ferguson 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 (H Show more

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

no PDF DOI: 10.1249/MSS.0000000000003964

BDNF brain-derived neurotrophic factor cerebrum childhood growth restriction chronic diseases high-intensity interval training neurodegenerative diseases neuroplasticity

NanoScript-Enabled Nonviral Transient Repression of Phosphatase and Tensin Homolog for Axonal Regeneration and Central Nervous System Injury Repair.

Brandon Conklin, Yanting Liu, Sarah Nevins +13 more · 2026 · ACS nano · ACS Publications · added 2026-04-24

Brandon Conklin, Yanting Liu, Sarah Nevins, Byeong-Gwan Song, Sy-Tsong Dean Chueng, Qiu Xiaowen, Sungyun Kim, Heyin Cheung, Seong Bae An, JongMin Lee, Bong Geun Chung, Wise Young, Dongming Sun, Hiroshi Sugiyama, Inbo Han, Ki-Bum Lee Show less

Spinal cord injury (SCI) remains a debilitating neurological disorder with limited therapeutic options, as existing treatments primarily address symptoms rather than address the complex interplay of c Show more

Spinal cord injury (SCI) remains a debilitating neurological disorder with limited therapeutic options, as existing treatments primarily address symptoms rather than address the complex interplay of cellular and molecular barriers to regeneration. These barriers collectively hinder functional recovery, including inhibitory glial scarring, chronic neuroinflammation, intrinsic neuronal regenerative deficits, and disruption of the blood-spinal cord barrier (BSCB). To address these limitations, we developed NanoScript-PTEN (NS-PTEN), a nonviral nanoparticle platform that delivers synthetic transcription factors to transiently suppress phosphatase and tensin homolog (PTEN) expression. PTEN negatively regulates the PI3K/AKT/mTOR signaling axis, which is a critical determinant of neuronal survival and axonal growth. By reducing PTEN levels, NS-PTEN derepresses this pro-survival pathway, promoting neuronal regeneration in the injured spinal cord. By integrating a DNA-binding domain targeting the PTEN promoter, a transcriptional repression module, and a nuclear localization signal onto a gold nanoparticle (AuNP) scaffold, NS-PTEN achieves transient control over PTEN repression, reactivating pro-regenerative signaling while minimizing the risks of tumorigenesis associated with permanent gene silencing. In a clinically relevant contusion SCI rat model, NS-PTEN induced a coordinated series of structural and microenvironmental improvements that collectively support spinal cord repair. Histologically, NS-PTEN enhanced axonal continuity and remyelination, as evidenced by denser NF-positive fibers and substantially greater MBP preservation than in both the injury and AuNP groups. Concurrently, NS-PTEN markedly attenuated astroglial and microglial reactivity, reducing GFAP Show less

📄 PDF DOI: 10.1021/acsnano.5c13020

BDNF

Standardized alkali-treated Euglena gracilis β-glucan mitigates PM

Ye-Lim You, Ha-Jun Byun, Jin-Young Jeon +4 more · 2026 · Journal of ethnopharmacology · Elsevier · added 2026-04-24

Ye-Lim You, Ha-Jun Byun, Jin-Young Jeon, Bo-Ra Kim, Ji Eun Hwang, Jun Hee Lee, Hyeon-Son Choi Show less

Euglena gracilis has a history of traditional use in East Asia as a functional food with reported antioxidant and immunomodulatory benefits. This study investigates the pharmacological potential of it Show more

Euglena gracilis has a history of traditional use in East Asia as a functional food with reported antioxidant and immunomodulatory benefits. This study investigates the pharmacological potential of its bioactive component, standardized alkali-treated β-glucan (AEGB), in mitigating systemic toxicity induced by environmental pollutants, providing a rationale to investigate its protective effects in the context of particulate matter (PM2.5)-induced injury. To evaluate the protective effects of standardized alkali-treated E. gracilis β-glucan (AEGB) against PM2.5-induced pulmonary and cerebral toxicity in BALB/c mice via the lung-brain axis. AEGB was prepared and standardized to contain 93% (w/w) β-glucan. BALB/c mice were intranasally exposed to PM2.5 and orally administered AEGB (200/400 mg/kg). Efficacy was evaluated via BALF analysis, histopathology, and immunoblotting, focusing on MAPK, NF-κB, NRF2-HO-1, and CREB-BDNF-TrkB pathways. AEGB exhibited higher antioxidant activity than untreated β-glucan. In PM2.5-exposed mice, AEGB (400 mg/kg) reduced inflammatory cells in BALF by 69.5% and suppressed lung pro-inflammatory cytokines (IL-1β, IL-6). Histologically, it attenuated bronchial thickening and mucin production. In the brain, AEGB downregulated NF-κB by 72.1% and restored hippocampal neuronal area (+41.1%) and tight junction marker expression associated with blood-brain barrier integrity. At the molecular level, AEGB inhibited pulmonary MAPK/NF-κB and activated NRF2-HO-1, while enhancing the cerebral CREB-BDNF-TrkB neurotrophic pathway. AEGB mitigates PM2.5-induced damage in both lung and brain tissues, accompanied by anti-inflammatory and neuroprotective responses consistent with inter-organ inflammatory/oxidative pathways relevant to the lung-brain axis. These findings validate the potential of E. gracilis-derived β-glucan as a functional agent for preserving respiratory and neural health. Show less

no PDF DOI: 10.1016/j.jep.2026.121276

BDNF antioxidant beta-glucan environmental pollutants euglena gracilis immunomodulatory particulate matter pharmacological

Dieckol, a phlorotannin from Ecklonia cava, alleviates stress hormone-induced depressive-like behaviors through glucocorticoid receptor antagonism.

Inhye Park, Jung-Eun Lee, Minji Kim +5 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24

Inhye Park, Jung-Eun Lee, Minji Kim, Minseok Yoon, Min Jung Kim, Min-Sun Kim, Suengmok Cho, Min Young Um Show less

Depression imposes significant social, economic, and health burdens worldwide. Although phlorotannin-rich extract from Ecklonia cava (PS) and its active compound dieckol (DK) exhibit various biologica Show more

Depression imposes significant social, economic, and health burdens worldwide. Although phlorotannin-rich extract from Ecklonia cava (PS) and its active compound dieckol (DK) exhibit various biological activities, their antidepressant- and anxiolytic-like effects and underlying mechanisms remain unclear. This study investigated the antidepressant- and anxiolytic-like potential of PS and DK in a corticosterone (CORT)-induced mouse model of depression and anxiety, focusing on glucocorticoid receptor (GR) signaling. CORT-treated mice were orally administered PS or DK, and behavioral tests were performed to assess depressive- and anxiety-like behaviors. PS composition was analyzed using LC-MS/MS. Molecular docking predicted the binding of PS components to GR. GR nuclear translocation, target gene expression, and downstream signaling were examined using behavioral, molecular, and computational approaches. PS alleviated CORT-induced depressive- and anxiety-like behaviors, accompanied by reduced GR nuclear translocation, suppression of Mkp-1, and restoration of ERK-CREB-BDNF signaling. Molecular docking analysis predicted strong binding of DK to the GR ligand-binding domain. Consistently, DK reduced GR nuclear translocation and GRE binding, downregulated GR target genes (Mkp-1, Sgk-1, Fkbp5, and Bdnf), and restored ERK-CREB-BDNF signaling. In vivo, DK also improved CORT-induced behavioral deficits and normalized HPA axis activity and neurotransmitter levels. Collectively, our results suggest that DK, a major bioactive phlorotannin from E. cava, exerts antidepressant- and anxiolytic-like effects in association with modulation antagonism of GR signaling, highlighting its therapeutic potential as a natural GR-modulating agent for stress-related mood disorders. Show less

no PDF DOI: 10.1016/j.phymed.2026.157906

BDNF antidepressant anxiety corticosterone depression glucocorticoid receptor phlorotannin stress hormone

Vitisin B, extracted from Vitis vinifera, enhances memory function and neuroprotective effects in scopolamine-induced memory-impaired mice.

Won Seok Kim, Jeongyoon Choi, Seong-Seop Kim +9 more · 2026 · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · Elsevier · added 2026-04-24

Won Seok Kim, Jeongyoon Choi, Seong-Seop Kim, June Hee Kim, Young-Eun Han, Myoung Jin Kwak, Soo-Jin Oh, Bonggi Lee, Ik-Hyun Cho, Chun Whan Choi, Gyu-Sang Hong, Min Soo Kim Show less

Alzheimer's disease (AD) is characterized by progressive cognitive decline and memory dysfunction, with prominent roles in cholinergic deficits and synaptic plasticity impairments. Vitisin B, a resver Show more

Alzheimer's disease (AD) is characterized by progressive cognitive decline and memory dysfunction, with prominent roles in cholinergic deficits and synaptic plasticity impairments. Vitisin B, a resveratrol tetramer derived from Vitis vinifera, exhibits potent antioxidant and neuroprotective properties. However, its potential to influence cognitive function in AD models remains inadequately explored. In this study, we first tested vitisin B in an in vitro model using SH-SY5Y cells exposed to scopolamine-induced cytotoxicity, where vitisin B significantly enhanced cell viability and promoted cell survival. We evaluated its therapeutic potential in vivo using both systemic administration and direct delivery into the third ventricle of the brain in a scopolamine-induced AD mouse model. Across both administration routes, vitisin B exerted a broad pro-cognitive effect, restoring multiple domains of learning and memory disrupted by scopolamine. Vitisin B recovered spatial working memory in the Y-maze, normalized exploratory activity in the open field, improved recognition memory in the novel object recognition (NOR) test, and enhanced long-term memory retention in the passive avoidance assay. This treatment restored cognitive function, alleviated cholinergic deficits, increased hippocampal brain-derived neurotrophic factor (BDNF) levels, and enhanced synaptic plasticity. These results suggest that vitisin B exerts reliable cognitive and neuroprotective effects through both systemic and cerebral administration, highlighting its potential as a promising therapeutic compound for restoring cholinergic function and enhancing hippocampal synaptic plasticity in AD. Show less

no PDF DOI: 10.1016/j.biopha.2026.119019

BDNF alzheimer's disease antioxidant cholinergic cognitive function memory neuroprotection synaptic plasticity

Developing digital biomarker for predicting cognitive response to multi-domain intervention.

Ji Hyeun Park, Hyun Sook Kim, Seong Hye Choi +7 more · 2026 · Scientific reports · Nature · added 2026-04-24

Ji Hyeun Park, Hyun Sook Kim, Seong Hye Choi, Jee Hyang Jeong, So Young Moon, Yoo Kyoung Park, Chang Hyung Hong, Soo Hyun Cho, Hae Ri Na, Hang-Rai Kim Show less

Computerized cognitive training allows real-time tracking of performance metrics that may serve as digital biomarkers. This study investigated the value of a novel in-game digital biomarker, RTACC (Re Show more

Computerized cognitive training allows real-time tracking of performance metrics that may serve as digital biomarkers. This study investigated the value of a novel in-game digital biomarker, RTACC (Reaction Time-Accuracy Correlation), the correlation between reaction time and accuracy, using data from 130 participants with mild cognitive impairment enrolled in the intervention arm of the SUPERBRAIN-MEET randomized controlled trial. Participants underwent a 24-week multi-domain intervention, consisting of computerized cognitive training, physical exercise, nutritional education, vascular/metabolic risk management, and motivation enhancement. RTACC was derived from task-level RT and accuracy and examined in relation to cognitive and biomarker outcomes. Linear regression analysis revealed a significant association between RTACC and changes in Repeatable Battery for the Assessment of Neuropsychological Status scores from baseline to 24 weeks (beta coefficient = -11.90 ± 3.78, T = - 3.14, P = 0.002). RTACC also showed a marginal effect on changes in brain-derived neurotrophic factor levels (beta coefficient = - 3.13 ± 1.64, P = 0.057). Logistic regression analysis demonstrated that RTACC combined with clinical information identified good responders with an area under the receiver operating characteristic curve of 0.73 (95% CI: 0.62-0.84). These findings suggest that this in-game digital biomarker (RTACC) may help identify individuals likely to benefit from multi-domain intervention. Show less

📄 PDF DOI: 10.1038/s41598-026-37123-8

BDNF

Sex-specific difference on anxiety- and depressive-like behavior in neuronal growth regulator 1-knockout mice.

So Rok Lee, Eunji Yoon, Sooyeon Baek +5 more · 2026 · Biology of sex differences · BioMed Central · added 2026-04-24

So Rok Lee, Eunji Yoon, Sooyeon Baek, Jin Gyeom Kim, Jong-Oh Kim, Su-In Yoon, Soojin Lee, Jin Ah Cho Show less

Sex differences are evident in anxiety and depression, and women more frequently present with comorbid anxiety and depression alongside gastrointestinal disturbances. This pattern suggests contributio Show more

Sex differences are evident in anxiety and depression, and women more frequently present with comorbid anxiety and depression alongside gastrointestinal disturbances. This pattern suggests contributions from sex-specific biological mechanisms and gut-brain communication. Negr1, a molecule regulating neuronal growth and connectivity, has been linked to depression-relevant behaviors in animal models. However, its mechanisms and potential sex-specific effects remain unclear. Behavioral tests were used to assess phenotypes related to depression, anxiety, and learning in male and female wild-type (WT) and Negr1 Negr1 This study demonstrates that, in Negr1 Show less

📄 PDF DOI: 10.1186/s13293-025-00816-2

BDNF

Sex-specific Serum Biomarker Associations with Antidepressant Treatment Outcomes in Depressive Disorders.

Jae-Min Kim, Hee-Ju Kang, Ju-Wan Kim +5 more · 2026 · Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · added 2026-04-24

Jae-Min Kim, Hee-Ju Kang, Ju-Wan Kim, Min Jhon, Min-Gon Kim, Ju-Yeon Lee, Sung-Wan Kim, Il-Seon Shin Show less

This study examined whether baseline levels of 14 serum biomarkers predicted antidepressant remission differently by sex at 12 weeks and 12 months. In a prospective cohort, 1,086 outpatients with depr Show more

This study examined whether baseline levels of 14 serum biomarkers predicted antidepressant remission differently by sex at 12 weeks and 12 months. In a prospective cohort, 1,086 outpatients with depressive disorders received stepwise antidepressant treatment following a naturalistic protocol. Baseline serum samples were analyzed for biomarkers from six systems: immune (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-4, interleukin-10), metabolic (leptin, ghrelin, total cholesterol), neurotrophic (brain-derived neurotrophic factor), neurotransmitter (serotonin), endocrine (cortisol), and nutritional (folate, homocysteine). Remission, defined as a Hamilton Depression Rating Scale scores ≤ 7, was assessed at 12 weeks and 12 months. Logistic regression models with biomarker-by-sex interaction and stratified analyses were used, adjusting for clinical covariates. Higher baseline serotonin predicted 12-week remission in males but not in females. At 12 months, lower leptin and higher folate predicted remission only in males, while lower cortisol predicted remission only in females. These showed significant biomarker-sex interactions. No sex-specific interactions were found for immune markers. Baseline serum biomarkers across biological systems showed sex-specific associations with treatment outcomes. Neurotransmitter, metabolic, endocrine, and nutritional markers may offer predictive value for sex-tailored, biomarker-informed treatment strategies in depression. Show less

📄 PDF DOI: 10.9758/cpn.25.1331

BDNF

Amygdala-hippocampus circuit regulates stress coping via mGluR5-dependent BDNF signaling.

Tae-Eun Kim, Tae-Yong Choi, Ja Wook Koo +1 more · 2026 · Molecules and cells · Elsevier · added 2026-04-24

Tae-Eun Kim, Tae-Yong Choi, Ja Wook Koo, Jeongseop Kim Show less

Stress-related psychiatric disorders are underpinned by dysfunction in the prefrontal cortex and hippocampus; however, the underlying circuit-specific mechanisms remain ill-defined. Here, we identifie Show more

Stress-related psychiatric disorders are underpinned by dysfunction in the prefrontal cortex and hippocampus; however, the underlying circuit-specific mechanisms remain ill-defined. Here, we identified the basolateral amygdala (BLA)-to-ventral hippocampus (vHPC) circuit as a critical regulator of stress-coping behaviors. Although chronic social defeat stress reduced the mGluR5 expression in both the vHPC and medial prefrontal cortex (mPFC), our circuit-specific behavioral analysis revealed that the activation of the BLA-vHPC circuit produced a significantly greater improvement in coping behavior compared with the activation of the BLA-mPFC circuit. Subsequently, we mechanistically demonstrated that reduced mGluR5 in the vHPC directly impairs CREB-mediated brain-derived neurotrophic factor (BDNF) transcription, a molecular cascade tightly linked to passive coping. These findings reveal a novel circuit-specific molecular mechanism governing stress recovery, positioning the mGluR5-BDNF pathway as a highly specific and promising therapeutic target for future gene therapy interventions. Show less

📄 PDF DOI: 10.1016/j.mocell.2026.100320

BDNF

Electroacupuncture mitigates Bacillus Calmette-Guérin (BCG)-induced depression-like behavior and neuroinflammation via BDNF and NF-κB pathway in mice.

Bombi Lee, Yoongeum Kim, Han-Chang Lee +2 more · 2026 · Animal cells and systems · Taylor & Francis · added 2026-04-24

Bombi Lee, Yoongeum Kim, Han-Chang Lee, Hyungjun Kim, Dae-Hyun Hahm Show less

Depression induce by chronic neuroinflammation disrupts daily life and work, underscoring the importance of its treatment. It this study, depressive- and anxiety-like behaviors were induced in mice by Show more

Depression induce by chronic neuroinflammation disrupts daily life and work, underscoring the importance of its treatment. It this study, depressive- and anxiety-like behaviors were induced in mice by injecting bacillus Calmette-Guérin (BCG), resulting from chronic neuroinflammation. Daily stimulation with specific acupuncture points (Baihui and Yintang, GV20 and GV29) with electroacupuncture (EA) for 14 days significantly alleviated depressive- and anxiety-like behaviors. Additionally, it also markedly reduced the levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β, and tumor necrosis factor-α, as well as inflammatory markers such as cyclooxygenase-2, in both the plasma and hippocampus. EA Stimulation significantly increased brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus. Our results demonstrated that EA stimulation improved depression- and anxiety-like behaviors induced by chronic inflammation, an effect associated with the decreased expression of BDNF via regulation of NF-κB pathway. Show less

📄 PDF DOI: 10.1080/19768354.2026.2614126

BDNF

👤 Dong Ha Kim