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Attention deficit hyperactivity disorder(ADHD), a common neurodevelopmental disorder in children, is characterized by inattention, hyperactivity, and impulsivity. Epidemiological surveys show that the prevalence of ADHD in children is gradually increasing worldwide, and it is the most common childhood mental disorder in China. Because of the complex clinical symptoms, multiple co-morbidities, and unknown etiology, ADHD has far-reaching negative impacts on individuals, families, and the society. Behavioral interventions, as a pillar in the management of ADHD, play a targeted role in improving children's social functioning, with significant benefits supported by evidence. However, they are constrained by uneven resources, poor compliance, and insufficient continuity, Western medicine has multiple adverse effects and unclear long-term effects in the treatment of ADHD despite the definite efficacy. Accordingly, there is an urgent need to find safe and effective therapies suitable for children. With a holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has significant advantages in treating ADHD via multiple targets, which involves dopamine(DA), norepinephrine(NE), 5-hydroxytryptamine(5-HT), cyclic adenosine monophosphate(cAMP), brain-derived neurotrophic factor(BDNF) and other signaling pathways. Through these pathways, TCM can treat ADHD through the regulation of neurotransmitters, enhancement of prefrontal and striatal functions, enhancement of neuronal protection, attenuation of neuroinflammation, and reduction of neuronal apoptosis. However, a systematic study remains to be conducted. This paper summarizes the signaling pathways related to the treatment of ADHD by TCM in the past two decades, aiming to provide reference for delving into the mechanism and exploring effective TCM prescriptions for ADHD in children and to give full play to the advantages of the efficacy and characteristics of TCM. Show less

The brain-derived neurotrophic factor ( A total of 43 first-episode mania patients (FEM), 110 multiple-episode mania patients (MEM) and 80 healthy controls were enrolled in our study. We investigated the impact of We found a significant interaction between This is the first study to demonstrate that The online version contains supplementary material available at 10.1186/s12888-026-07949-7. Show less

Emerging evidence underscores the central role of the retinal neurovascular unit (RNVU) in the pathogenesis of major retinal disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Traditionally considered as primarily vascular diseases, these conditions are now increasingly recognized to involve early neurodegenerative processes that may precede vascular dysfunction. Although anti-VEGF therapies have revolutionized the treatment of neovascular retinal diseases, long-term VEGF inhibition has been associated with adverse effects, including retinal atrophy and diminished neuroprotection, underscoring the need for more targeted strategies. Recent studies have highlighted the differential roles of VEGF-A splice isoforms, particularly the pro-angiogenic VEGF-Axxxa and the anti-angiogenic VEGF-Axxxb, in maintaining RNVU homeostasis and contributing to disease progression. In parallel, neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have demonstrated the ability to exert neuroprotective, anti-inflammatory, and vasomodulatory effects, partly through modulation of VEGF-A signaling. Notably, we have recently demonstrated that NGF modulates VEGF-A isoform expression and VEGFR-2 levels in diabetic retinas, further supporting the hypothesis of a functional cross-talk between neurotrophins and angiogenic pathways. Based on this evidence, a new model is proposed, in which NGF and BDNF interact bidirectionally with VEGF-A to preserve RNVU integrity. This integrated therapeutic perspective, combining neurotrophic support with selective modulation of VEGF-A isoforms, may enhance treatment efficacy, reduce long-term side effects, and minimize the burden of care in chronic retinal neurodegenerative diseases. Show less

This study aimed to explore whether the BDNF Val66Met polymorphism influences early cortical plasticity, as measured by TMS-EEG, and its impact on rTMS therapy response in anterior-circulation ischemic stroke, with outcomes evaluated at day 14 and day 90 post-stroke. We retrospectively analyzed 200 patients genotyped for BDNF Val66Met: Val/Val (n = 102), Val/Met (n = 79), and Met/Met (n = 19). Demographic and clinical data were collected, and each patient underwent TMS-EEG before rTMS. Neurological status (NIHSS and mRS) was assessed at day 14 and day 90 post-stroke. Plasticity was measured using the composite plasticity index, N100, P30, SICI, and ICF. Clinical endpoints included NIHSS change, responder rate, and mRS distribution. Baseline profiles were comparable across groups. The genotype distribution was consistent with Hardy-Weinberg equilibrium and comparable to that of the general population. Val/Val carriers showed the most pronounced plasticity (plasticity index: 0.22 ± 0.06 vs. 0.12 ± 0.06 vs. 0.07 ± 0.06; p < 0.001). Clinically, Val/Val patients showed greater NIHSS improvement at both day 14 (ΔNIHSS: 7.4 vs. 5.3 vs. 4.9) and day 90 (8.2 vs. 6.0 vs. 5.1; p < 0.001). Responder rates were highest in Val/Val (p = 0.0045 at day 14, p = 0.0235 at day 90), with better mRS distribution (p < 0.001). The plasticity index positively correlated with ΔNIHSS (r = 0.58 at day 14; r = 0.61 at day 90; both p < 0.001) and negatively with mRS (r=-0.52; p < 0.001). The BDNF Val66Met polymorphism significantly modulates cortical excitability and functional recovery following stroke. Our findings indicate that TMS-EEG plasticity mediates the relationship between genotype and rTMS efficacy, supporting its potential as a biomarker for personalized rehabilitation strategies. Show less

Acute exercise modulates circulating exerkines and affective states, yet it remains unclear whether mind-body exercise modalities, such as yoga, elicit responses observed in aerobic exercise. This study examined the acute effects of yoga, stretching, moderate-intensity aerobic exercise, and low-intensity aerobic exercise on exerkines and affect. Eighty-eight adults (52% female; mean age = 23.3 ± 5.79 years) were randomized to one of two study arms: aerobic exercise (moderate-intensity = 70-75% heart rate max and low-intensity = 40-50% heart rate max) or mind-body exercise (yoga and stretching). At two laboratory visits, participants completed 30-minutes of each condition within their assigned arm in a counterbalanced order. Venous blood collected immediately before and after exercise was analyzed for brain-derived neurotrophic factor (BDNF) and endocannabinoids (N-arachidonoylethanolamine [AEA], 2-arachidonoylglycerol [2-AG]). State anxiety and positive and negative affect were assessed pre- and post-exercise. Linear mixed-effects models tested pre-to-post changes and condition interactions. Moderate-intensity aerobic exercise increased circulating concentrations of AEA (b = 0.10, p = .005), while 2-AG and BDNF concentrations were unchanged across conditions. All four exercise conditions decreased state anxiety and negative affect, whereas only yoga, stretching, and moderate-intensity aerobic exercise increased positive affect. Pre-to-post AEA increases were correlated with changes in positive affect (b = 0.18, p = .041). In this randomized study-arm design, moderate-intensity aerobic exercise uniquely increased AEA, whereas affective improvements were observed across modalities. These findings implicate cardiovascular intensity in the endocannabinoid response to exercise, while diverse forms of acute exercise are associated with short-term affective benefits. 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

Post-traumatic stress disorder (PTSD) is a chronic psychiatric condition linked with abnormal fear responses, oxidative imbalance, inflammation, and neuronal injury. The present work examined the protective effects of morin hydrate (MH), a natural flavonoid known for its antioxidant and neuroprotective properties, in a stress-re-stress (SRS) rat model of PTSD. Male Wistar rats were exposed to repeated stress cues and then treated with vehicle, paroxetine (10 mg/kg, p.o.), or MH (15 and 30 mg/kg, p.o.). Behavioral outcomes were assessed using fear conditioning, elevated plus maze, open field, Y-maze, novel object recognition, forced swim, and sucrose preference tests. Animals exposed to SRS developed pronounced fear retention, anxiety-like and depressive behaviors, and cognitive impairment. Treatment with MH, especially at 30 mg/kg, improved exploratory activity, reduced immobility, and enhanced memory performance. Biochemical studies showed reduced lipid peroxidation and restoration of glutathione, superoxide dismutase, and catalase. MH also lowered pro-inflammatory cytokines (TNF-α, IL-1β) and increased hippocampal brain-derived neurotrophic factor (BDNF). Histological analysis confirmed preservation of neuronal density in CA1 and CA2 regions of the hippocampus. In summary, MH produced behavioral, biochemical, and structural improvements in the SRS model, suggesting its value as a natural therapeutic candidate for PTSD. Show less

Press needle therapy, may alleviate depressive-like behaviors. Male rats were randomly allocated into four groups ( Press-needle ameliorated depressive-like behaviors in CUMS-exposed rats, restored body weight gain and improved behavioral performance. The treatment upregulated the hippocampal BDNF/TrkB/CREB signaling pathway, increasing BDNF, TrkB, CREB, AKT, and PI3K in the hippocampus. The therapy modulated serotonergic neurotransmission by increasing hippocampal 5-HTT expression, while downregulating 5-HT1A and 5-HT2C receptors and PKA. Notably, press-needle exerted anti-neuroinflammatory effects, reducing hippocampal and serum levels of TNF-α and IL-6. Histopathological analysis confirmed its neuroprotective efficacy, demonstrating attenuated neuronal damage in hippocampal tissues. 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

Chronic toxoplasmosis has been increasingly associated with behavior disorders, including depression-like behaviors, while the underlying mechanisms remain poorly understood. In this study, we demonstrated that chronic toxoplasmosis induced depression-like behaviors in mice, which were observed together with neuroinflammation, neuronal injury, and suppression of the BDNF-TrkB pathway. Treatment with the TrkB agonist 7,8-DHF alleviated these behavioral deficits by restoring BDNF-TrkB signaling, preserving neuronal function, and reducing neuroinflammation through inhibition of NF-κB and MAPK pathways. Additionally, 7,8-DHF also reduced astrocyte overactivation and protected blood-brain barrier structure integrity. These findings highlight that disruption of BDNF-TrkB signaling contributes to T. gondii-induced behavioral abnormalities and that targeting this pathway may represent a promising therapeutic strategy against neuroinflammation and neuronal damage associated with chronic infection. Show less

Decline in mitochondrial quality is a prominent pathological feature of Alzheimer's disease (AD), manifested by impaired energy metabolism, disrupted mitochondrial biogenesis, abnormal mitochondrial dynamics, and defective mitophagy. Increasing evidence indicates that mitochondrial dysfunction contributes to the exacerbation of amyloid-β (Aβ) deposition and tau protein hyperphosphorylation, thereby accelerating AD pathogenesis. Of particular interest, physical exercise has been shown to effectively enhance mitochondrial quality and help prevent or slow the progression of AD, largely through the activation of key signaling pathways such as adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). However, regular physical activity may not be feasible for individuals in the prodromal or clinical stages of AD. In this context, exercise mimetics-compounds that pharmacologically simulate the molecular effects of exercise-have emerged as a promising alternative intervention. This review analyzes the mechanistic roles of exercise mimetics in improving mitochondrial quality under AD conditions, with a focus on their regulation of mitochondrial homeostasis via key signaling pathways. It further aims to provide theoretical insight for the development of mitochondria-targeted exercise mimetics and offer a potential strategy for addressing the growing global burden of AD. Show less

Alzheimer's disease features early a pathology in the locus coeruleus (LC), yet how sex and life experience shape LC vulnerability remains poorly understood. We expressed pseudophosphorylated human tau (htauE14) in LC neurons of TH-Cre rats and exposed both sexes to early- or late-life enrichment or stress. Behavioral, histological, protein, and hippocampal single-nucleus RNA sequencing (snRNA-seq) analyses were performed. LC-targeted htauE14 impaired learning and increased anxiety-like behavior. Early enrichment reduced htauE14 spread and LC microglia activation, elevated hippocampal brain-derived neurotrophic factor (BDNF), and improved olfactory learning in males. Late enrichment alleviated anxiety and enhanced spatial memory, whereas late stress exacerbated LC degeneration. Hippocampal snRNA-seq revealed sex- and cell type-specific transcriptional responses, with htauE14 preferentially engaging metabolic and synaptic pathways in females, effects amplified by early stress but stabilized by early enrichment. Late-life experiences primarily recruited homeostatic regulatory programs. Sex and developmental history critically shape early LC tau-related vulnerability. Show less

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder defined by progressive cognitive impairment, neuroinflammation, oxidative stress, amyloid-β (Aβ) accumulation, synaptic dysfunction, mitochondrial impairment, and tau hyperphosphorylation. The gut-brain axis (GBA) is a crucial regulatory signaling cascade that links intestinal microbiome composition with both neural health and disease through the vagus nerve. Gut dysbiosis has increasingly been implicated in AD pathogenesis by exacerbating systemic and neuroinflammatory signaling, disrupting intestinal and blood-brain barrier (BBB) structural stability, and promoting microglial activation, thereby facilitating Aβ aggregation and neurodegeneration. Preclinical studies indicate that symbiotic interventions restore microbial balance and improve gut-brain communication, contributing to neuroprotective effects. Additionally, it has been demonstrated that symbiotics can restore synaptic plasticity and cognitive resilience by suppressing pro-inflammatory cytokines, as exemplified by interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), and by upregulating neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF). These effects are associated with normalised glial reactivity, attenuation of oxidative stress, and improved mitochondrial bioenergetics, together contributing to enhanced synaptic function, reduced neuroinflammation, and preservation of cognitive performance. This review highlights a critical assessment of the treatment potential of symbiotic interventions in modulating the GBA in AD, emphasising mechanistic insights into neurodegenerative pathways and evaluating their capacity to mitigate symptoms and delay disease progression, as supported by current preclinical evidence. Show less

Chaihu Shugan San (CSS), a classical Traditional Chinese Medicine (TCM) formula, was first recorded in Jingyue Quanshu (1624 AD) for treating "liver qi stagnation" (Yu Syndrome), a TCM diagnostic pattern analogous to modern mood disorders. Although CSS has been prescribed for emotional distress, irritability, and depressive symptoms for centuries, the neurobiological mechanisms underlying its antidepressant efficacy, particularly in the context of gender-specific pathology, remain poorly revealed. The present study probed the antidepressant effects of CSS in female mice, while elucidating the underlying molecular mechanisms involving hippocampal neuroinflammation and neuroplasticity. We hypothesized that CSS reverses chronic stress-induced depressive phenotypes by suppressing interleukin-6 (IL-6), which in turn facilitates cAMP-CaMKII-BDNF signaling pathway in the hippocampus. Adult female C57BL/6J mice were subjected to a 5-week chronic unpredictable mild stress (CUMS) regimen to evoke depressive-like behaviors. During the final 2 weeks of the regimen, CSS was administered intragastrically at 0.5, 1.0, or 1.5 g/kg, with fluoxetine (10 mg/kg) as the positive control. Behavioral assessments included forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), and tail suspension test (TST). Hippocampal IL-6, cAMP, CaMKII, and BDNF levels were quantified by ELISA. Mechanistic validation employed acute hippocampal microinjection of recombinant IL-6 (1 μg/site) and systemic administration of the CaMKII inhibitor KN-93 (6 mg/kg). Chemical constituents were identified by UHPLC-QTOF MS. CSS alleviated CUMS-induced depressive-like behaviors in a dose-dependent manner, cutting down immobility time in TST/FST and reinstating sucrose preference, similar to the action of fluoxetine. CSS significantly suppressed hippocampal IL-6 while upregulating cAMP, CaMKII activity, and BDNF expression. Acute IL-6 elevation completely abolished both the behavioral antidepressant effects and molecular actions of CSS. Pharmacological inhibition of CaMKII blocked CSS-induced behavioral improvement and its upregulation of cAMP-BDNF signaling, without affecting basal behaviors. CSS exhibited no anxiogenic or locomotor side effects. CSS exerts potent antidepressant effects in female mice through coordinated suppression of hippocampal IL-6 and activation of the cAMP-CaMKII-BDNF neuroplasticity-related pathway, with CaMKII playing a critical role in this process. These findings offer scientific evidence for the traditional use of CSS in addressing emotional disorders and highlight its therapeutic potential as a multi-targeted, anti-inflammatory botanical medicine for female-specific depression. Show less

A single nucleotide polymorphism in the brain derived neurotrophic factor (BDNF)-encoding gene leads to diminished BDNF signaling resulting from Val66Met and has been linked to obesity. Previous imaging studies regarding the impact of BDNF Val66Met on the central serotonin system, which is involved in behavior, cognition and control of satiety, have not focused on body weight or food-intake related behavior. We revisited a cohort of thirty non-depressed individuals with obesity and 15 normal-weight controls. 29 obese and 13 controls underwent [ Show less

This research evaluated the efficacy of Withaferin A-conjugated mesoporous silica nanoparticles (WA-MSNs) in accelerating the restoration of neural tissue and improving the recovery of sensory and motor functions following a sciatic nerve injury (SNI) in male Wistar rats. WA-MSNs were evaluated for encapsulation efficiency, drug release, particle size, surface charge, and molecular interactions. A rat SNI model was created, and subjects were treated with WA-MSNs, free WA, unloaded MSNs, or received no treatment. The sham group was also included for comparison. Regeneration was measured through the sciatic functional index (SFI), Hargreaves test, and electrophysiology (CMAP and NCV). Complementary assessments included sciatic nerve histomorphometry, assessment of gastrocnemius muscle mass, and Enzyme-Linked Immunosorbent Assay (ELISA) for inflammatory cytokines and neurotrophic factors. WA-MSNs achieved a 74.6% encapsulation efficiency and provided sustained drug release over 72 h. DLS analysis showed a monodisperse colloidal system, with an average hydrodynamic diameter of approximately 198 nm and a zeta potential of -22.4 mV. WA-MSN-treated rats exhibited significantly faster motor and sensory recovery compared to controls (p < 0.001), with electrophysiological parameters approaching those of sham-treated rats. Histological analysis revealed improved axonal morphology, myelination, and recovery of gastrocnemius muscle mass. ELISA results showed modulation of cytokine profiles, characterized by a marked reduction in (IL-1β, IL-6, TNF-α), and substantial elevation in the levels of (IL-10, TGF-β), and elevated neurotrophic factors (NGF, BDNF, NT-3). WA-MSNs significantly promote functional and histological nerve regeneration after SNI by modulating inflammation and enhancing neurotrophic support. These findings support WA-MSNs as a promising therapeutic approach for clinical peripheral nerve repair. Show less

Premature ejaculation (PE) is one of the most common forms of male sexual dysfunction, yet its underlying neurobiological mechanisms remain unclear. This study aims to explore the role of S100 calcium-binding protein B (S100B) in PE and its regulatory relationship with brain-derived neurotrophic factor (BDNF) and serotonin (5-HT) signaling. A rat model of PE was established using behavioral screening criteria. Sexual behavior parameters were recorded, and the expression levels of S100B, BDNF, and 5-HT in brain tissues were measured using enzyme-linked immunosorbent assay, quantitative real-time PCR, Western blotting, immunohistochemistry, and immunofluorescence. The impact of S100B knockdown on PE-related behaviors and molecular expression was evaluated. The primary outcome was the effect of S100B regulation on PE-related behaviors and its interaction with the BDNF/5-HT signaling pathway. PE rats exhibited classical behavioral features, including shortened ejaculation latency and increased ejaculation frequency. Transcriptomic and protein analyses showed that S100B expression was significantly upregulated, while BDNF and 5-HT levels were markedly reduced in PE rats. S100B expression increased across several brain regions. Knockdown of S100B restored 5-HT and BDNF levels, prolonged ejaculation latency, and alleviated PE behaviors. BDNF overexpression elevated 5-HT levels and improved sexual behavior. Importantly, BDNF silencing reversed the beneficial effects of S100B knockdown, suggesting that S100B regulates ejaculation via the BDNF/5-HT pathway. Targeting S100B and its regulation of the BDNF/5-HT pathway may provide potential therapeutic strategies for managing premature ejaculation. Strengths include comprehensive molecular and behavioral analyses in a rat model provide insights into PE pathophysiology. Although this effect has been demonstrated in animal models, these models may not fully recapitulate the pathophysiological processes of human PE, and further clinical validation is required. Our findings indicate that S100B is upregulated in PE and may contribute to the pathophysiology of PE by modulating the BDNF/5-HT signaling pathway. This study provides a molecular basis for the development of therapeutic strategies targeting PE. Show less

Lung cancer remains a leading cause of cancer-related mortality worldwide. Depression, highly prevalent in lung cancer patients, not only impairs quality of life but also adversely affects disease progression and treatment outcomes through complex biological pathways. Previously considered merely a psychological reaction, depression is now recognized as sharing bidirectional pathophysiological interactions with lung cancer. This narrative review comprehensively reviews current evidence on the molecular mechanisms linking depression to lung cancer progression, with a focus on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS), cytokine-mediated inflammation, and the lung-brain axis involving BDNF/TrkB signaling. We also discuss the potential therapeutic implications of antidepressants, including their effects on apoptosis, autophagy, and immune modulation. Key findings suggest that depression promotes tumor progression via chronic stress pathways, while antidepressants may counter these effects through multiple mechanisms. Understanding these pathways may inform integrated treatment strategies and improve prognosis in lung cancer with comorbid depression. Show less

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with distinct subtypes, relapsing MS (RMS) and primary progressive MS (PPMS), which differ in clinical course and underlying immunopathology. Cytokines are pleiotropic mediators of inflammatory and regenerative processes and are considered important contributors to the pathophysiology of MS. Ocrelizumab, a CD20-targeting monoclonal antibody, is approved for the treatment of patients with RMS and PPMS, yet its effects on circulating cytokines and neurotrophic factors remain incompletely understood. In this prospective observational study, 84 patients with MS (57 RMS, 27 PPMS) were analyzed regarding demographic data, disease activity and serum cytokine profiles before and 6 months after the start of ocrelizumab therapy. Baseline analyses revealed distinct cytokine signatures between patients with RMS and PPMS, with higher levels of several proinflammatory cytokines and chemokines in patients with RMS. Following ocrelizumab treatment, divergent cytokine profiles between patients with RMS and PPMS were partially attenuated, with significant modulation of Th1-associated chemokines and an increase in brain-derived neurotrophic factor (BDNF) observed in patients with RMS. In contrast, cytokine signatures in patients with PPMS remained largely unaffected by ocrelizumab treatment. Patients with RMS with disease activity during the first 6 months of ocrelizumab treatment showed a significant increase in different chemokines compared to baseline compared with patients without disease activity or those with PPMS. Our findings support divergent immunological mechanisms in RMS and PPMS, with a stronger cytokine-driven pathology and more pronounced immunomodulatory effects of ocrelizumab on the cytokine profile in patients with RMS. Show less

To analyse the effects of noise exposure in emergency resuscitation rooms (ERRs) on cognitive function and hyperalgesia in patients with trauma. Clinical data from 110 patients with trauma who were treated in the ERR of Suizhou Central Hospital between June 2022 and July 2023 were retrospectively analysed. Participants were divided into the following two groups on the basis of real-time noise monitoring: the high-noise-exposure (n = 85) and low-noise-exposure (n = 25) groups. Neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), homocysteine (Hcy), the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA) were used to measure cognitive performance. Mechanical pain threshold and serum nerve growth factor (NGF), substance P (SP), calcitonin gene-related peptide (CGRP) and 5-hydroxytryptamine (5-HT) levels were applied to assess hyperalgesia. Pearson correlation was employed to investigate the connections between noise levels and outcome factors. The high-noise-exposure group demonstrated significantly lower MMSE scores, MoCA scores and serum BDNF levels but higher serum NSE and Hcy levels compared with the low-noise-exposure group (P < 0.05). Additionally, compared with the low-noise-exposure group, the high-noise-exposure group exhibited larger mechanical hyperalgesia areas around incisions and on the volar forearm, as well as elevated serum CGRP, NGF and SP levels, while showing reduced mechanical pain thresholds and lower serum 5-HT levels (P < 0.05). Pearson analysis revealed that noise exposure values had negative correlations with mechanical pain threshold, MMSE and MoCA scores and serum BDNF and 5-HT levels (r < 0, P < 0.05) but positive correlations with mechanical hyperalgesia area and serum CGRP, NSE, Hcy, NGF and SP levels (r > 0, P < 0.05). High noise exposure in ERRs may be associated with cognitive dysfunction and hyperalgesia in patients with trauma. Clinical management should recognise and control noise levels in these settings. Show less

Exercise has been shown to support brain health, cognitive function, and increase levels of brain-derived neurotrophic factor (BDNF). While BDNF is known to support the central nervous system through improved brain metabolism, vasculature, neurotransmission and synaptic plasticity, the association between exercise-induced changes in BDNF concentrations and exercise-related cognitive improvements is still unclear. This study investigated the relationship between exercise-induced changes in plasma BDNF (pBDNF) and serum BDNF (sBDNF), and haemodynamic indicators of prefrontal cortex function in sedentary adults. Participants (n = 23, female = 7) were randomized into intervention (12-week cycling programme) and control groups (no intervention). Participants completed V̇O Show less

The underlying mechanisms for exacerbated brain injury and poor recovery observed in patients with diabetes and ischemic stroke (IS) remain undetermined. We explored the role of microRNA-34a (miR-34a) in diabetic IS (DMIS) and ischemic postconditioning (IPOC)'s neuroprotective effects in tree shrews. We established a tree shrew DMIS model and exposed it to interventions, including miR-34a inhibition (antagomir), IPOC, and miR-34a overexpression (agomir). Infarct size and pathology were assessed via staining. Cellular/molecular changes (astrocytes, neurons, brain-derived neurotrophic factor [BDNF], Sine oculis homeobox 3 [SIX3], proliferation, apoptosis, axon formation) were analyzed using immunofluorescence, polymerase chain reaction (PCR), and Western blotting. In vitro, miR-34a's targeting of BDNF/SIX3 was validated, with rescue experiments testing regulation via these factors. Infarct size and neuronal damage were greater in the DMIS group than in the nondiabetic IS group. miR-34a inhibition or IPOC reduced infarcts, alleviated injury, improved cell survival, upregulated BDNF/SIX3, enhanced proliferation/axon formation, and reduced apoptosis. miR-34a overexpression reversed IPOC's benefits. In vitro, miR-34a directly targeted BDNF/SIX3, suppressing their expression; exogenous BDNF/SIX3 rescued neurotoxicity and restored function. IPOC exerts partial neuroprotection through miR-34a downregulation, highlighting miR-34a as a potential therapeutic target. Show less

Neuroplasticity is the core process by which the brain responds to aging, learning, and injury. Reporting positive non-pharmacological intervention approaches to promote neural plasticity is a core focus of contemporary neuroscience and rehabilitation medicine. Tai Chi (TC), as a traditional Chinese physical and mental practice that deeply combines soothing body movements, breathing regulation, and spiritual focus, is increasingly attracting attention from the scientific community for its role in facilitating brain health. Our review seeks to combine recent evidence, elucidate how TC promotes neural plasticity via multi-level mechanisms, discuss its advantages in promoting cognitive, motor, and emotional functions, and investigate its clinical utilization prospects and future research challenges in neurorehabilitation. According to reviewing recent literature, we combined evidence from cross-sectional studies, randomized controlled trials, systematic reviews, and meta-analyses, with a center on citing research findings utilizing multimodal neuroimaging techniques (such as fMRI, fNIRS, EEG) and molecular biology techniques to construct a complete chain of evidence from molecules to systems. TC drives multi-level neural plasticity modifications via its unique physical and mental combination properties. At the macro level, it can enhance the gray matter volume of the hippocampus and prefrontal cortex, and promote the organizational effectiveness of large-scale functional networks in the brain. At the micro molecular level, TC establishes a favorable microenvironment for neuronal survival, synaptic plasticity, and neural repair by upregulating BDNF, increasing endogenous antioxidant defense, modulating inflammatory balance, and improving mitochondrial energy metabolism. These structural, functional, and molecular level changes collectively form the neurobiological basis for TC to promote memory and executive function, increase balance and motor management, and promote emotional regulation ability. Our review further assesses the clinical effectiveness of TC in the rehabilitation of neurological diseases, such as Parkinson's disease (PD), stroke, and mild cognitive impairment, determining that it not only decreases symptoms, but may also have the possible role to decrease disease development. Ultimately, our review delve into the challenges and future perspectives experienced by this range in the context of standardization of research paradigms, causal reasoning of mechanisms, and individualized interventions. Show less

Despite the growing interest in cell- and exosome-based therapies for neurological diseases including Alzheimer's disease (AD), there is still a gap in the investigation of more effective treatments in terms of efficacy, safety, and durability of effect. This study aimed to compare the therapeutic potential of astrocyte cells and their derived exosomes (AS-Exos) in restoring cognitive function in a mouse model of AD. AD model was induced by bilateral electrical lesioning of the nucleus basalis of Meynert (NBM). Astrocytes were isolated from neonatal rat brains, and AS-Exos were harvested from astrocyte-conditioned media using an AnaCell extraction kit. Seven days after lesion induction, astrocytes and AS-Exos were stereotaxically injected into the NBM. Four weeks later, behavioral assessments (passive avoidance and locomotor activity), electrophysiological recordings (EEG), and biochemical measurements of hippocampal brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels were performed. AS-Exos were confirmed as cup-shaped vesicles (30-150 nm) expressing the exosomal surface markers CD9, CD63, and CD81. NBM lesions significantly reduced step-through latency (STL), hippocampal BDNF and ACh levels, and disrupted EEG oscillatory patterns. Treatment with AS-Exos markedly improved STL and produced greater increases in hippocampal BDNF and ACh levels compared with AD and AD+saline groups. EEG analysis also revealed enhanced beta, alpha, and gamma power, with the most robust normalization observed in the AS-Exos group. AS-Exos demonstrated superior biochemical and electrophysiological benefits compared with astrocyte transplantation and provided equal or greater improvement in behavioral outcomes. These findings highlight AS-Exos as a promising cell-free therapeutic strategy for alleviating cognitive deficits associated with AD. Show less

Microglial decline in the dentate gyrus is an important mechanism in the development of depression-like behaviors in stressed animals. Reversing this decline with low-dose lipopolysaccharide (LPS) can produce rapid antidepressant effects, yet the underlying mechanisms remain incompletely understood. Our previous work identified a critical role for astrocytic P2Y1 receptor (P2Y1R) activation and subsequent dentate gyrus extracellular signal-regulated kinase 1/2 (ERK1/2)-brain-derived neurotrophic factor (BDNF) signaling in the antidepressant effect of low-dose LPS. This study elucidates the signaling cascade linking astrocytic P2Y1R mobilization to the antidepressant effect of low-dose LPS. We found that low-dose LPS promoted glutamate release through ATP-triggered astrocytic P2Y1R signaling. Blockade of N-methyl-D-aspartic acid (NMDA) receptors, but not metabotropic receptors, and the GluN2B subtype of NMDA receptors abolished the antidepressant effect of low-dose LPS. GluN2B knockdown also abolished the reversal effect of low-dose LPS on CUS-induced depression-like behaviors and impairment of dentate gyrus ERK1/2-BDNF signaling. Moreover, chelating intracellular Ca Show less

Remote ischemic preconditioning (RIpreC) is a strategy for remotely protecting target organs such as the brain by applying brief ischemia and reperfusion to the limb. However, the mechanisms underlying RIpreC-induced neuroprotection remain unclear. We aimed to investigate the neuroprotective effects of RIpreC on the peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α)/ fibronectin type III domain-containing protein 5 (FNDC5)/ brain-derived neurotrophic factor (BDNF) pathway in rat models of ischemic stroke. Rats were assigned to three groups: ischemia-reperfusion injury (IR, The online version contains supplementary material available at 10.1007/s12975-026-01422-z. Show less

Dementia involves progressive cognitive decline, impairing daily and social activities. As no current drugs can reverse this decline, preventive strategies using functional compounds are gaining attention. Rutin, a flavonoid with neuroprotective and vascular benefits, has limited bioavailability due to poor water solubility. Although enzymatic glycosylation improves its solubility, it contains multiple compounds with differing numbers of sugar units and is not a single compound. To address this, EubioQuercetin®, a novel water-soluble rutin (wsRutin) formulation, was developed using L-arginine and ascorbic acid, without enzymatic processing. Here, we evaluated the neuroprotective effects of quercetin and isorhamnetin, the major metabolites of rutin, and compared the cognitive effects of rutin suspension and wsRutin solution in mice. Quercetin and isorhamnetin suppressed glutamate-, menadione- and H Show less

West Nile virus (WNV), an arbovirus of emerging global interest, can cause neuroinvasive disease in humans. Currently, no protective vaccine or specific treatment is available for human WNV encephalitis. The virus induces neuronal cell death, while astrocytes and microglia cells are suspected to contribute to WNV pathology. Hence, understanding their role is crucial for future treatment approaches. In this study, we establish a WNV encephalitis model using human cerebral organoids, generated with male iPSCs. Infection results in heterogeneous kinetics with an early strong replication potentially leading to viral clearance, while a late peak was associated with more long-term infection. Viral foci are seen in cortical-like areas, rich in neurons and astrocytes, however void of microglia. Pro-inflammatory cytokines (IL-6, TNF-α, IL-18), chemokines (CXCL10, CCL17, CX3CL1, CCL2) and biomarkers (IL-1RA, sTREM-1, sRAGE, BDNF) are increasingly released. Conclusively, human cerebral organoids make suitable WNV encephalitis models with valuable properties to study acute and long-term infection. Show less

Upwards of 50% of people do not respond to the primary treatment modalities for major depressive disorder (MDD), which has led to increased attention and use of alternative methods, including exercise and psychedelics. While interventions using either exercise or psychedelics have demonstrated largely positive results in isolation, their synergistic potential has yet to be explored. As such, this commentary provides an overview of exercise/psychedelics as a treatment for depression and their potential synergy and/or complementarity. From a biological perspective, psychedelics acutely enhance brain-derived neurotrophic factor (BDNF) signalling, while exercise provides sustained BDNF elevation; psychedelics enhance neuroplasticity largely in the cortex (with only modest effects in the hippocampus), while exercise boosts hippocampal neurogenesis; psychedelics increase glutamate release via stimulation of 5-HT Show less