Brain Research Bulletin[JOURNAL]
Sun
200 papers
p75 neurotrophin receptor exacerbates neuronal apoptosis after intracerebral hemorrhage by promoting OTUB1 ubiquitination and degradation.
Cui R, Yuan H, Tang Y … +5 more , Xue X, Song Y, Tao H, Ke K, Shen J
Brain Res Bull · 2026 Aug · PMID 42229638 · Publisher ↗
Intracerebral hemorrhage (ICH) remains a devastating subtype of stroke with extremely high mortality and long-term neurological disability worldwide, and secondary neuronal apoptosis is the core pathological event drivin...
Intracerebral hemorrhage (ICH) remains a devastating subtype of stroke with extremely high mortality and long-term neurological disability worldwide, and secondary neuronal apoptosis is the core pathological event driving poor functional prognosis in ICH patients. However, the precise molecular mechanisms governing post-ICH neuronal apoptosis still remain poorly defined, and effective targeted therapeutic strategies for ICH are still lacking clinically. Here we show that the p75 neurotrophin receptor (p75NTR) exacerbates ICH-induced neuronal injury by promoting the degradation of the deubiquitinase OTUB1. In a mouse model of ICH and hemin-treated HT22 hippocampal neurons, p75NTR and OTUB1 were significantly upregulated and co-localized in the cytoplasm. p75NTR directly interacted with OTUB1 through its intracellular domain (ICD). Functionally, p75NTR overexpression promoted K48-linked polyubiquitination and proteasomal degradation of OTUB1, leading to an increased Bax/Bcl-2 ratio and elevated cleaved caspase-3 levels. Rescue experiments validated that OTUB1 overexpression effectively reversed neuronal apoptosis triggered by p75NTR, whereas OTUB1 knockdown aggravated this apoptotic process. Collectively, our findings uncover a novel p75NTR-OTUB1 signaling cascade that modulates neuronal apoptosis following ICH. This work provides new mechanistic insight into post-ICH brain injury and offers a promising molecular target for developing intervention strategies against ICH-induced neuronal loss.
Spatio-temporal dynamics of brain function across depression severity in binge-type eating disorders.
Zhang P, Tang L, Li W … +9 more , Wang M, Chen Q, Yu F, Yang Z, Li Z, Wang Z, Wang Y, Wu G, Wang J
Brain Res Bull · 2026 Aug · PMID 42229637 · Publisher ↗
Functional connectivity (FC) and intrinsic neural timescales (INT) characterize the spatio-temporal neural dynamics of binge-type eating disorders (EDs). We examined FC and INT abnormalities in visual-related regions of...
Functional connectivity (FC) and intrinsic neural timescales (INT) characterize the spatio-temporal neural dynamics of binge-type eating disorders (EDs). We examined FC and INT abnormalities in visual-related regions of patients with binge-type EDs, focusing on the impact of depression severity. We recruited 72 patients with binge-type EDs and 39 healthy controls (HCs). Patients were divided into two groups: Group 1 (minimal/mild depression) and Group 2 (moderate/severe depression). FC alterations in key visual-related regions across three groups were analyzed using ANCOVA (P < 0.05, FWE-corrected). INT was further assessed in regions with significant FC changes (P < 0.05, FDR-corrected). Correlations of FC and INT with clinical measures, as well as between FC and INT, were examined. Seventeen brain subregions exhibited altered FC, with Group 2 showing more pronounced disruptions than Group 1 and HCs. These alterations primarily involved nodes within the sensorimotor, reward, and inhibitory control networks. Additionally, significant INT differences in the sensorimotor and heteromodal regions were observed between Group 2 and HCs. Correlation analyses suggested trend-level associations between FC and clinical characteristics, as well as between FC and INT in Group 2. Collectively, these findings indicate that FC and INT disruptions in visual-related regions are aggravated by depression severity in binge-type EDs.
Stress granules and tau pathology in Alzheimer's disease: A scoping review of bidirectional interactions, liquid-liquid phase separation, and proteostatic consequences.
Ashrafi Kashtiban B, Rezazadeh M, Gharesouran J … +2 more , Jafari B, Ghafouri-Fard S
Brain Res Bull · 2026 Aug · PMID 42225170 · Publisher ↗
BACKGROUND: Alzheimer's disease (AD) is characterized by progressive neurodegeneration driven by amyloid-β (Aβ) plaques and tau neurofibrillary tangles. Stress granules (SGs), dynamic ribonucleoprotein condensates formed...
BACKGROUND: Alzheimer's disease (AD) is characterized by progressive neurodegeneration driven by amyloid-β (Aβ) plaques and tau neurofibrillary tangles. Stress granules (SGs), dynamic ribonucleoprotein condensates formed under cellular stress have been implicated in several neurodegenerative disorders, but their role in AD pathogenesis remains incompletely understood. METHODS: Following PRISMA-ScR guidelines, we systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library (through February 2026) for peer-reviewed studies investigating SGs in AD models or human tissue. Two reviewers independently screened records, extracted data, and performed narrative synthesis. RESULTS: Thirty-five studies met inclusion criteria. TIA1 (51.4%) and G3BP1 (42.9%) were the most frequently used SG markers. Multi-model designs incorporating human tissue validation predominated (40.0%). Evidence suggests a bidirectional pathogenic interplay: tau pathology promotes SG assembly and persistence, while SG proteins, particularly TIA1 and USP10 can drive tau oligomerization and toxicity via liquid-liquid phase separation in experimental models. Additional SG network components, including HDAC6 and TRIM21, have been independently implicated in AD pathology, though they remain less explored in direct SG-tau interaction studies. Conversely, G3BP2 exerts protective effects by directly binding tau and inhibiting aggregation. SG dysregulation is associated with disrupted RNA metabolism, sequesteration of AD-associated transcripts, and impaired autophagy. Therapeutic strategies targeting SG modulation, including autophagy enhancers (mTOR inhibitors, myricetin), show promise in reducing tau pathology and SG burden in preclinical systems. CONCLUSION: The reviewed evidence suggests that SGs are associated with AD pathogenic processes through bidirectional interactions with tau pathology, RNA dysregulation, and proteostatic collapse. These findings, derived largely from preclinical models, support further investigation into SG modulation as a potential therapeutic strategy for AD, while definitive causal roles in human disease remain to be established.
Frequency-specific alterations of spontaneous brain activity in stroke patients with upper limb motor dysfunction: A multi-metric rs-fMRI and machine learning study.
Tang Z, Dong L, Li H … +9 more , Ren W, Long J, Liao X, Han K, Chen J, Ling Z, Zhang X, Zhang H, Chi Q
Brain Res Bull · 2026 Aug · PMID 42219043 · Publisher ↗
BACKGROUND: Post-stroke upper limb motor dysfunction is associated with complex alterations in brain function, but the frequency-specific characteristics of spontaneous local neural activity remain incompletely understoo...
BACKGROUND: Post-stroke upper limb motor dysfunction is associated with complex alterations in brain function, but the frequency-specific characteristics of spontaneous local neural activity remain incompletely understood. This study investigated multi-metric resting-state functional magnetic resonance imaging (rs-fMRI) alterations in stroke patients with upper limb motor dysfunction and explored their discriminative value using machine-learning classifiers. METHODS: A total of 70 stroke patients and 45 healthy controls (HCs) underwent rs-fMRI. Fractional amplitude of low-frequency fluctuations (fALFF), percent amplitude of fluctuation (PerAF), and wavelet transform-based amplitude of low-frequency fluctuations (Wavelet-ALFF) were calculated across the conventional band (0.01-0.08 Hz), Slow-4 band (0.027-0.073 Hz), and Slow-5 band (0.01-0.027 Hz). Voxel-wise group comparisons were performed with age, sex, and mean framewise displacement as covariates. Lesion mapping, lesion-volume analysis, and a subcortical-lesion subgroup sensitivity analysis were conducted to assess lesion-related effects. Regional features showing significant group differences were used to construct support vector machine (SVM), Random Forest, and XGBoost classifiers, and model performance was evaluated on an independent testing set. RESULTS: Compared with HCs, stroke patients showed widespread frequency-specific alterations in cerebellar, visual, cingulo-motor, temporal, insular, subcortical, and frontal regions. Core abnormalities in cerebellar, visual, cingulate, supplementary motor, and frontal regions were largely retained in the subcortical-lesion subgroup. Lesion volume was negatively correlated with Fugl-Meyer Assessment for Upper Extremity scores. Several nominal associations were observed between Slow-5 fALFF features in visual regions and motor impairment severity, but none survived false discovery rate correction. Among all testing-set models, the SVM classifier using combined multi-metric Slow-4 and Slow-5 features achieved the highest numerical performance, with an AUC of 0.956, accuracy of 0.912, sensitivity of 0.905, and specificity of 0.923. However, DeLong tests showed no statistically significant superiority of sub-frequency features over conventional-band features. CONCLUSIONS: Stroke patients with upper limb motor dysfunction exhibit distributed, frequency-specific alterations in spontaneous local brain activity. Multi-metric rs-fMRI features, particularly combined sub-frequency features, may have exploratory discriminative value, but external validation is needed before they can be considered robust imaging biomarkers.
Benefits of 12-week self-paced training combined with melatonin supplementation on oxidative stress, inflammation, hyperlipidemia, and body composition in multiple sclerosis patients: A randomized controlled trial.
Jallouli S, Jallouli D, Kallel C … +8 more , Sakka S, Damak M, Jaafar B, Mhiri C, de Marco G, Driss T, Ayadi F, Hammouda O
Brain Res Bull · 2026 May · PMID 42217742 · Publisher ↗
BACKGROUND: Concurrent aerobic-resistance training has been reported to be beneficial for oxidative stress, inflammation, hyperlipidemia, and body composition in patients living with multiple sclerosis (PwMS). Exogenous...
BACKGROUND: Concurrent aerobic-resistance training has been reported to be beneficial for oxidative stress, inflammation, hyperlipidemia, and body composition in patients living with multiple sclerosis (PwMS). Exogenous melatonin also showed its anti-oxidant and anti-inflammatory effects in this population. However, no previous study has associated training with melatonin in PwMS despite their endogenous melatonin deficiency. To enhance the training's benefits, we aimed to investigate the impact of 12-week self-paced training combined with melatonin supplementation on biological adaptations and body composition in PwMS. METHODS: Forty-nine PwMS participated in this parallel and randomized controlled study. Participants were randomly assigned to four groups: training + melatonin (TMG, n = 11), training + placebo (TPG, n = 11), melatonin (MG, n = 15), or placebo (PG, n = 12). All groups ingested either melatonin or placebo (3 mg/night), while only the TMG and TPG additionally performed a concurrent training based on two aerobic high-intensity interval exercises and four resistance exercises (3 times/week, in the afternoon). Selected biochemical and hematological parameters as well as body composition were assessed pre- and post-intervention. RESULTS: Levels of reduced glutathione, total bilirubin, and uric acid increased in TMG comparatively with TPG (all: p < 0.001) and MG (p = 0.002; p = 0.0002; p < 0.001, respectively). The TMG showed a decrease in malondialdehyde, advanced oxidation protein products, and low-density lipoprotein cholesterol levels compared with TPG (p < 0.001; p = 0.038; p = 0.0003, respectively) and MG (p = 0.0034; p = 0.004; p < 0.001, respectively). There was a decrease in white blood cell, neutrophil, and lymphocyte counts in TMG comparatively with TPG (p = 0.0005; p = 0.0001; p = 0.014, respectively) and MG (p = 0.023; p = 0.007; p = 0.026, respectively). Lean mass increased (p = 0.025) while fat mass (p = 0.0013) and body mass index (p = 0.034) decreased in TMG compared with TPG. CONCLUSION: Concurrent training combined with melatonin supplementation showed greater anti-inflammatory, antioxidant and hypolipidemic effects than each intervention alone, and was more beneficial than training alone for body composition in PwMS.
Peripheral to central: Exploring the neural, endocrine, and immune pathways of the gut-brain axis in postoperative neurocognitive dysfunction.
Cao R, Shi Z, Ou W … +1 more , Liu Z
Brain Res Bull · 2026 Aug · PMID 42217741 · Publisher ↗
Perioperative neurocognitive dysfunction (PND), a common complication associated with anesthesia and surgery, has garnered considerable interest regarding its underlying mechanisms. However, the precise pathways through...
Perioperative neurocognitive dysfunction (PND), a common complication associated with anesthesia and surgery, has garnered considerable interest regarding its underlying mechanisms. However, the precise pathways through which PND develops remain incompletely understood. Accumulating evidence suggests that dysfunction of the microbiota-gut-brain axis (MGBA) plays a pivotal role in the pathogenesis of PND. Accordingly, this article reviews current advances in the understanding of MGBA-mediated mechanisms contributing to PND, with a focus on neurological, endocrine, and immune pathways. Specifically, we discuss the involvement of the sympathetic, vagal, and enteric nervous systems, neuroinflammation within the central nervous system, the stress response and glucocorticoid signaling, microbial metabolites, and specific inflammatory factors and signaling pathways in the development of PND. Furthermore, targeting the gut microbiota may represent a promising therapeutic strategy for PND. This review aims to provide insights beneficial to both clinical management and future research on PND.
Toward convenient depression detection using two non-hair-bearing frontal EEG channels.
Wei B, Jiang X, Liu W … +6 more , Yang Z, Bian X, Sun Y, Li G, Yu X, Zhang X
Brain Res Bull · 2026 Aug · PMID 42217740 · Publisher ↗
BACKGROUND: Depressive disorder (DD) is a prevalent mental illness with substantial impacts on emotional, cognitive, and physical functioning. The diagnosis of DD however is heavily relying on subjective assessments. Alt...
BACKGROUND: Depressive disorder (DD) is a prevalent mental illness with substantial impacts on emotional, cognitive, and physical functioning. The diagnosis of DD however is heavily relying on subjective assessments. Although some exploratory works proposed objective detection methods based upon EEG signals, the widely-used high-density setup significantly limits its practicability and convenience. METHODS: Here, we introduced an analysis framework for convenient DD detection using EEG data recorded at two non-hair-bearing (NHB) frontal channels (Fp1 and Fp2) from 80 participants (controls/patients = 38/42). Multiscale coarse-graining strategies were then employed on the EEG data to construct scale-dependent temporal representations, where EEG features were extracted on such reconstructed temporal sequences and set as input for the following classification models. The impact of various settings (i.e., window length of EEG data, coarse-graining designs, and scale factors) was also quantitatively investigated. RESULTS: We achieved satisfactory performance (> 88%) for DD classification using NHB EEG signals. Further analyses showed that moderately long window (> 12s) providing more stable performance. Moreover, overlapping coarse-graining strategies exhibited superior robustness in comparison with non-overlap strategy. Incorporating multiscale temporal representations consistently improved discriminative capability. CONCLUSIONS: These findings indicate that under frontal NHB EEG configurations, multiscale temporal organization is not merely an optional enhancement but a necessary representational strategy for reliable DD detection. The proposed framework provides practical guidance for developing efficient, wearable EEG-based systems for depression screening in real-world settings.
Graph theory analysis of resting-state fMRI identified neural correlates of disease severity and surgical prognosis in degenerative cervical myelopathy.
Ge Y, Li H, Chen Q … +4 more , Xia J, Wang Y, Xue Y, He D
Brain Res Bull · 2026 Aug · PMID 42208820 · Publisher ↗
OBJECTIVE: To investigate the neural correlates of the mismatch between the degree of spinal cord compression and the severity of symptoms in degenerative cervical myelopathy (DCM) patients using graph theory analysis an...
OBJECTIVE: To investigate the neural correlates of the mismatch between the degree of spinal cord compression and the severity of symptoms in degenerative cervical myelopathy (DCM) patients using graph theory analysis and to explore its value in predicting prognosis. METHODS: We collected clinical data and resting-state fMRI data from 54 DCM patients and 50 healthy controls (HC). We constructed networks based on the Automated Anatomical Labeling template and performed graph theory analyses. In analysis 1, we investigated intergroup differences in graph theory metrics. In analyses 2 and 3, we examined differences in metrics between mild symptom patients and severe symptom patients after eliminating the confounding effect of compression degree. In analysis 4, we tested the utility of the graph theory metrics that exhibited significant intergroup differences for predicting patient prognosis. RESULTS: Small-world architecture in networks was identified in all the participants. Compared to HC, DCM patients exhibited higher global efficiency in global network metrics and abnormal nodal topological properties which were predominantly in sensorimotor cortex, default mode network, prefrontal network and visual network. The metrics showing significant abnormalities in DCM patients overlapped spatially with those showing inter-group differences both between mild symptom and severe symptom patients, and between severe compression but mild symptoms and mild compression but severe symptoms patients. The prognostic model incorporating graph theory metrics can predict postoperative outcomes. CONCLUSION: Abnormal network topology in DCM patients influences disease severity and can provide information for predicting patient prognosis.
Large-scale network distribution of resting-state functional abnormalities in chronic kidney disease and their relation to cognitive impairment.
Wang YF, Chen HJ, Yang YT … +2 more , Kong X, Zhang LJ
Brain Res Bull · 2026 Jul · PMID 42208819 · Publisher ↗
Emerging evidence suggests that cognitive impairment in chronic kidney disease (CKD) reflects dysfunction of large-scale brain networks rather than focal regional abnormalities. However, the distribution of resting-state...
Emerging evidence suggests that cognitive impairment in chronic kidney disease (CKD) reflects dysfunction of large-scale brain networks rather than focal regional abnormalities. However, the distribution of resting-state functional abnormalities across large-scale brain networks remains unclear. We analysed resting-state functional magnetic resonance imaging (rs-fMRI) data from 380 patients with CKD and 404 healthy controls (HCs) from an initial cohort of 1246 participants. CKD patients were further stratified into end-stage renal disease (ESRD) and non-ESRD subgroups. All participants completed neuropsychological testing and underwent rs-fMRI. Five established voxel-wise rs-fMRI measures-amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), binarized degree centrality (BDC), and weighted degree centrality (WDC)-were calculated and compared between groups. We then examined associations among imaging measures, clinical variables, and cognitive performance. Patients with CKD showed significant cognitive deficits relative to HCs, and similar patterns were observed in the ESRD versus non-ESRD comparison (all P < 0.05). Whole-brain analyses revealed widespread functional abnormalities, predominantly within the default mode network (DMN) and frontoparietal network (FPN). A similar network-level distribution was also observed in the ESRD versus non-ESRD comparison. Mediation analysis showed that reduced ALFF in the inferior parietal lobule (IPL) statistically mediated the association between lower haematocrit (HCT) and worse Line Tracing Test (LTT) performance, suggesting an anaemia-related pathway linking reduced spontaneous neural activity to cognitive dysfunction. These findings indicate that the DMN and FPN are the principal large-scale networks affected in CKD and identify IPL dysfunction as a potential target for future interventions for CKD-related cognitive impairment.
Co-administration of quercetin and NLRP3 inhibitor attenuates inflammation and oxidative stress in cuprizone-induced demyelination model.
Nourmohammadi F, Javan A, Shirzad M … +2 more , Sadeghi F, Ghasemi-Kasman M
Brain Res Bull · 2026 Jul · PMID 42203077 · Publisher ↗
Quercetin (Qur), as a natural plant-derived flavonoid with antioxidant and neuroprotective properties, and MCC950, a selective NLRP3 inflammasome inhibitor, have each demonstrated notable pharmacological activities, incl...
Quercetin (Qur), as a natural plant-derived flavonoid with antioxidant and neuroprotective properties, and MCC950, a selective NLRP3 inflammasome inhibitor, have each demonstrated notable pharmacological activities, including antioxidant and anti-inflammatory effects. The present study examined the combined impacts of Qur and MCC950 on oxidative stress, demyelination, and inflammation in the cuprizone (CPZ)-induced demyelination model. To induce demyelination, CPZ (0.2% w/w) was incorporated into the normal diet of male C57BL/6 mice for 42 days. Subsequently, animals received Qur (25 mg/kg/day, oral), MCC950 (5 mg/kg/day, i.p), or their combination for 14 days. Working memory was evaluated using the Y-maze test. FluoroMyelin staining and GFAP immunofluorescence were used to assess the extent of demyelination and astrocyte activation, respectively. Oxidative stress and antioxidant biomarkers, including MDA, TOS, TAC, SOD, CAT, and GPx, were measured using colorimetric techniques. The expression levels of oligodendrocyte markers, antioxidant signaling, and pro-inflammatory cytokines, including MBP, PDGFRα, Olig2, Nrf2, HO-1, NQO1, GSK3β, IL-1β, IL-18, and TNF-α, were assessed by qRT-PCR. Our results indicated that co-administration of Qur and MCC950 improved working memory and restored antioxidant capacity. A significant reduction was found in the extent of demyelination, astrocytic reactivity, and inflammatory mediator expression in treated mice. Moreover, combined treatment elevated the expression levels of pro-myelinating and antioxidant markers more effectively than either agent alone. Our findings indicate that inhibiting the NLRP3 inflammasome and enhancing antioxidant defenses promote remyelination and confer neuroprotective effects by reducing oxidative stress and inflammation, likely through modulation of glial responses.
Distinct preoperative multimodal brain reorganizations underlie differential outcomes of DREZ lesioning for neuropathic pain after spinal cord injury.
Chen Q, Li X, Wang L … +6 more , Chen Z, Zhang Y, Becker L, Hu Y, Wang Z, Chen N
Brain Res Bull · 2026 Jul · PMID 42202434 · Publisher ↗
Dorsal root entry zone (DREZ) lesioning is an established neurosurgical procedure for treating refractory neuropathic pain (NP) after spinal cord injury (SCI). To identify preoperative neuroimaging biomarkers associated...
Dorsal root entry zone (DREZ) lesioning is an established neurosurgical procedure for treating refractory neuropathic pain (NP) after spinal cord injury (SCI). To identify preoperative neuroimaging biomarkers associated with surgical outcomes, we analyzed 24 SCI-NP participants who showed differential responses to DREZ lesioning. We hypothesized that preoperative alterations in white matter integrity, brain structure, and functional connectivity (FC), particularly within the descending pain modulatory system, would differ between participants with effective versus ineffective surgical outcomes. Based on the extent of postoperative pain relief, participants were classified into an effective group (EG) and an ineffective group (IG). Preoperative multimodal MRI was obtained, including diffusion tensor imaging (DTI), 3D high-resolution T1-weighted structural imaging (extending to the cervical 5 level), and resting-state functional data. Cervical level C2/C3 macrostructure parameters were measured employing the Jim 7.0 software. Tract-based spatial statistics was performed on DTI data, and voxel-based morphometry was carried out for structural images. For functional MRI data, regions showing significant structural alterations were used as seeds to compute FC. Compared to the EG, the IG exhibited increased mean diffusivity (MD) in the bilateral internal capsule and axial diffusivity (AD) in the right corticospinal tract, along with increased gray matter volume in the periaqueductal gray (PAG). Using the PAG as a seed, the IG showed reduced FC between the PAG and the left primary sensorimotor cortex. No significant differences between groups were found in spinal cord macrostructure. These findings demonstrate that participants with different outcomes exhibit distinct preoperative patterns of brain reorganization, particularly in the PAG and its sensorimotor connectivity. These findings suggest that preoperative multimodal MRI may help identify participants unlikely to benefit from DREZ lesioning, potentially guiding surgical candidacy and personalized treatment planning.
Classification of familial and non-familial ADHD using auto-encoding network and binary hypothesis testing.
Baboli R, Martin E, Qiu Q … +5 more , Zhao L, Liu T, Wu K, Gao Y, Li X
Brain Res Bull · 2026 Jul · PMID 42190896 · Full text
Family heritage is one of the most powerful risk factors for attention-deficit/hyperactivity disorder (ADHD). Children with familial ADHD (ADHD-F) and non-familial ADHD (ADHD-NF) have both shared and distinct behavioral...
Family heritage is one of the most powerful risk factors for attention-deficit/hyperactivity disorder (ADHD). Children with familial ADHD (ADHD-F) and non-familial ADHD (ADHD-NF) have both shared and distinct behavioral characteristics and clinical outcomes, with their neuropathological underpinnings under-investigated. In this study, we utilized an autoencoder-based deep learning architecture within the binary hypothesis framework to identify the most important structural- and diffusion-MRI-based neural signatures that robustly discriminate 129 children with ADHD-F, 159 AHDH-NF, and 150 matched controls. Nested leave-one-out and five-fold methods were used for double cross-validations of the results. Classification accuracy, sensitivity, specificity, and area under the curve (AUC) were applied to evaluate the model performance. The model achieved accuracies of 65.4 ± 3.2, 67.0 ± 2.2, and 62.0 ± 4.9, with corresponding AUCs of 65.6 ± 4.8, 67.6 ± 5.2, and 65.8 ± 5.2, for ADHD-F vs. controls, ADHD-NF vs. controls, and ADHD-F vs. ADHD-NF, respectively. The most informative features for successful ADHD-F vs. control discrimination were mean diffusivity (MD) of right fornix, MD of left parahippocampal cingulum, and cortical thickness of right inferior parietal cortex. The key contributors for successful ADHD-NF vs. control discrimination were fractional anisotropy (FA) of left inferior fronto-occipital fasciculus, MD of right fornix, and cortical thickness of right medial orbitofrontal cortex. The highlighted features for successful ADHD-F vs. ADHD-NF discrimination were volume of left cingulate cingulum tract, volume of right parietal segment of the superior longitudinal fasciculus, and cortical thickness of right fusiform cortex. Our binary hypothesis semi-supervised deep learning framework robustly discriminated familial vs. non-familial ADHD and provided validated neural features that have potential to serve as distinct treatment targets of ADHD-F vs. ADHD-NF.
Formyl peptide and its receptor system as a novel target for the prevention and treatment of neuroinflammation-related diseases.
Zhu Z, Yin X, Li R … +7 more , Huang W, Yao Y, Lin H, Yin S, Li B, Ou Q, Zhou S
Brain Res Bull · 2026 Jul · PMID 42190895 · Publisher ↗
Neuroinflammation is a hallmark pathological feature of various central nervous system (CNS) disorders. Persistent activation can trigger an imbalance between pro- and anti-inflammatory homeostasis, thereby exacerbating...
Neuroinflammation is a hallmark pathological feature of various central nervous system (CNS) disorders. Persistent activation can trigger an imbalance between pro- and anti-inflammatory homeostasis, thereby exacerbating neuronal injury, demyelination, and blood-brain barrier (BBB) disruption, ultimately leading to irreversible loss of neurological function. Formyl peptides and their receptors are critical drivers of neuroinflammation. As members of the G protein-coupled receptor (GPCR) family, formyl peptide receptors (FPRs) primarily recognize exogenous bacterial formyl peptides and endogenous damage-associated peptides, thereby modulating pathophysiological processes such as immune cell chemotaxis, inflammatory cytokine release, and tissue repair. Recent studies have demonstrated that FPRs are functionally expressed in microglia, astrocytes, and neurons of the CNS. Aberrant activation or silencing of FPRs is closely linked to the initiation, maintenance, and resolution of neuroinflammation and plays a pivotal role in neuroinflammation-related diseases. This review focuses on the mechanisms by which the formyl peptide/receptor system mediates neuroinflammation in neural cells. Furthermore, we propose potential therapeutic strategies targeting FPRs to modulate neuroinflammation and provide new perspectives for the prevention and treatment of neuroinflammation-related disorders.
From protector to perpetrator: The cGAS-STING pathway at the intersection of neurodegeneration and neuroinflammation.
Oriquat G, Abdulqader AF, Farid H … +5 more , Ashurov Z, Sottarov A, Ghafl NY, Bainsal N, Singh R
Brain Res Bull · 2026 Jul · PMID 42190894 · Publisher ↗
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, a cornerstone of the innate immune system designed to combat pathogens, is now implicated as a critical driver of sterile inflammation in...
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, a cornerstone of the innate immune system designed to combat pathogens, is now implicated as a critical driver of sterile inflammation in the brain. This review synthesizes compelling evidence that in the aging and diseased central nervous system, endogenous cytosolic DNA, sourced from genomic instability, mitochondrial dysfunction, and activated retrotransposons, hijacks this pathway. Chronic cGAS-STING activation transforms microglia into inflammatory amplifiers, instigates neurotoxic astrocyte programs, and directly compromises neuronal health, creating a self-perpetuating cycle of neuroinflammation. We dissect the cell-type specific consequences within the neurovascular unit and establish the pathway's role in the pathogenesis of ALS/FTD, Alzheimer's, Parkinson's, and Huntington's diseases. Crucially, we evaluate the therapeutic potential of targeting this axis, discussing small-molecule inhibitors, oligonucleotide therapies, and upstream interventions to quell the source of immunogenic DNA. We also explicitly examine contradictory preclinical data, including the retracted PINK1-Parkin-STING report and context-dependent neurovascular findings, to provide a balanced appraisal of STING biology in the CNS. By reconciling its dual protective and pathogenic roles, this review posits cGAS-STING as a pivotal mechanism-based therapeutic node for halting the progression of neurodegenerative disorders.
Brain tau network derived biomarker improves the diagnostic accuracy of Alzheimer's disease.
Pan T, Zhou Q, Li P … +5 more , Nie B, Li N, Yang H, Shan B, Li W
Brain Res Bull · 2026 Jul · PMID 42184907 · Publisher ↗
BACKGROUND: To develop and validate brain tau network based biomarker for the early diagnosis and prognostication of Alzheimer's disease (AD). A total of 456 subjects, including 226 healthy controls (HC), 166 mild cognit...
BACKGROUND: To develop and validate brain tau network based biomarker for the early diagnosis and prognostication of Alzheimer's disease (AD). A total of 456 subjects, including 226 healthy controls (HC), 166 mild cognitive impairment (MCI), and 64 AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI), were included in this study. Preprocessed F-AV1451 PET images and clinical assessments were used. Regional standardized uptake value ratios (SUVR) relative to the cerebellum were calculated using partial volume corrected PET images. For graphical analysis of brain network at individual level, thirty regional F-AV1451 SUVRs sampled for whole brain volume were used to compute network characteristics, including connectivity, nodal and global efficiency. Group differences in network characteristics were examined and four classification models based on different predictors were constructed. Cross-sectional and longitudinal verification were performed to assess the efficiency of the network characteristics. RESULTS: The cross-sectional and longitudinal results showed decreasing trends in connectivity, nodal and global efficiency from HC to MCI and AD. The results of the network-based model significantly enhanced the classification accuracy compared to the model only using SUVR as predictors. Notably, the apolipoprotein E4 (apoE4) positive participants exhibited reduced connectivity, nodal efficiency, and global efficiency compared to the negative. CONCLUSIONS: The network characteristics calculated at the individual level, particularly the global efficiency of the brain tau network, are quantitative biomarkers for monitoring AD progression and evaluating therapeutic responses.
Enhanced engulfment by microglia and oligodendrocyte precursor cells contributes to synapse loss in the primary visual cortex following optic nerve injury.
Hu Q, Li D, Fu Y … +6 more , Zhang X, Huang Y, Zhang Y, Wang J, Liu L, Yu M
Brain Res Bull · 2026 Jul · PMID 42178114 · Publisher ↗
AIMS: To investigate the alterations of glial cells and synapses as well as their interactions in the primary visual cortex (V1) following optic nerve injury. METHODS: Bilateral V1 tissues of mice were collected 4 weeks...
AIMS: To investigate the alterations of glial cells and synapses as well as their interactions in the primary visual cortex (V1) following optic nerve injury. METHODS: Bilateral V1 tissues of mice were collected 4 weeks after unilateral optic nerve crush (ONC) or sham surgery. Synaptic changes were examined by transmission electron microscopy (TEM), immunofluorescence and western blot. Immunofluorescence assessed the quantity of glial cells and their engulfment of vGluT2. Quantitative real-time polymerase chain reaction (qPCR) and immunofluorescence evaluated the expression of phagocytic genes. RESULTS: In the contralateral V1 of ONC mice, presynaptic vesicles and PSD length decreased, synaptic puncta of SYP in L2/3, L4, and L6, as well as PSD95 and vGluT2 puncta in L4 reduced. Microglia, astrocytes, and oligodendrocyte precursor cells (OPCs) increased and phagocytosis analysis revealed enhanced vGluT2 engulfment by microglia and OPCs, but not astrocytes in the contralateral V1 of ONC mice. The number of vGluT2 puncta tagged by C1q, and the colocalization of microglia or OPCs with MERTK, were both elevated in the ONC-contra group. CONCLUSIONS: Optic nerve injury leads to synaptic impairment and glial cells alterations in the contralateral V1. Enhanced synaptic engulfment by microglia and OPCs contributes to synapse loss in the V1 after optic nerve injury.
EEG microstate dynamics and metal metabolism in Parkinson's disease dementia: An exploratory study with machine learning-assisted sensitivity analysis.
Guo W, Geng M, Chang Y … +5 more , Wang C, Zhang Y, Chen J, Zhao J, Wang T
Brain Res Bull · 2026 Jul · PMID 42178113 · Publisher ↗
BACKGROUND: Electroencephalogram (EEG) microstates effectively characterise cognitive-related brain networks, and metal homeostasis is crucial for maintaining cognitive function. However, the relationship between these f...
BACKGROUND: Electroencephalogram (EEG) microstates effectively characterise cognitive-related brain networks, and metal homeostasis is crucial for maintaining cognitive function. However, the relationship between these factors in Parkinson's disease (PD) with dementia (PDD) remains unclear. We investigated this association and evaluated the performance of these combined features in classifying PDD. METHODS: We analysed linear and nonlinear features of EEG microstates in 60 patients with PDD, 56 patients with PD without dementia (PDND), and 60 healthy controls (HC). We measured indicators of metal metabolism in patients with PD and examined correlations between their microstate characteristics, clinical scale scores, and metal metabolism levels. We trained a support vector machine (SVM) with these integrated features to differentiate PDD from PDND. RESULTS: (1) Compared with the PDND group, the PDD group showed increased occurrence and coverage of microstate A, prolonged duration of microstates B and C, increased occurrence of microstate C, but reduced occurrence and coverage of microstate B. Compared with HC, the PDND group showed decreased duration and occurrence of microstate C, along with prolonged duration of microstate B. Both PD subgroups showed lower nonlinear dynamic metrics than HC. (2) The PDD group had lower serum transferrin (STf) than PDND. Lower STf was associated with longer duration of microstate C and higher TP from microstate D to A. (3) Although microstate parameters achieved the highest area under the curve (AUC), the multimodal ensemble provided superior clinical utility for identifying PDD by maximizing recall and minimizing false negatives. CONCLUSIONS: Altered STf levels in PDD suggest an association between metal metabolism and brain network dysfunction relevant to pathophysiology. Integrating EEG microstates with metal metabolic indicators showed potential to enhance diagnostic sensitivity, warranting further investigation as a candidate approach for PDD identification.
Corrigendum to "Combination of electroacupuncture and Liqi Yangyin formula treatment alleviates cognitive impairment and constipation in D-gal-induced mice via modulation of the brain-gut axis" [Brain Res. Bull. 229 (2025) 111451].
Xu C, Shen P, Li Q … +4 more , Ong SS, Qian Y, Song Y, Xu T
Brain Res Bull · 2026 Jul · PMID 42177132 · Publisher ↗
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The effect of a single bout of moderate aerobic exercise on prefrontal activation during a cognitive-motor task in male university students: The moderating role of cardiorespiratory fitness.
Ye Y, Chen K, Lin H
Brain Res Bull · 2026 Jul · PMID 42176905 · Publisher ↗
OBJECTIVE: This study examined whether cardiorespiratory fitness (CRF) is associated with differences in behavioral performance and prefrontal oxygenated hemoglobin (Oxy-Hb) responses during a cognitive-motor dual task i...
OBJECTIVE: This study examined whether cardiorespiratory fitness (CRF) is associated with differences in behavioral performance and prefrontal oxygenated hemoglobin (Oxy-Hb) responses during a cognitive-motor dual task in male university students. METHODS: Forty male university students were classified into high-CRF and low-CRF groups based on maximal oxygen uptake (VO₂max). Participants completed a single 25-min bout of moderate-intensity cycling. Before and after this exercise bout, they performed a cycling-based dual task that combined steady-state cycling with Serial-7 subtraction. During the dual-task assessments, reaction time, accuracy, and task-evoked prefrontal Oxy-Hb responses were recorded using functional near-infrared spectroscopy. RESULTS: Compared with the low-CRF group, the high-CRF group showed better baseline dual-task accuracy and higher baseline Oxy-Hb in the left dorsolateral prefrontal cortex. Following exercise, the high-CRF group demonstrated greater improvement in reaction time. Group differences in exercise-related changes in Oxy-Hb were also observed in the right dorsolateral prefrontal cortex and frontopolar area, although only the right dorsolateral prefrontal cortex effect remained significant after correction for multiple comparisons. Regression analyses further showed that VO₂max significantly predicted post-exercise reaction time, accuracy, and Oxy-Hb responses in selected prefrontal regions. CONCLUSION: CRF was associated with both baseline dual-task performance and post-exercise changes in behavioral performance and prefrontal Oxy-Hb responses. These findings are consistent with the view that higher cardiorespiratory fitness may be linked to more favorable neurocognitive responses following acute moderate-intensity exercise.
Zinc exacerbates tau-induced neuronal damage and autophagy dysfunction by inhibiting the Akt/mTOR pathway.
Li X, Liao J, Wang J … +2 more , Zhao J, Liu Z
Brain Res Bull · 2026 Jul · PMID 42176904 · Publisher ↗
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder in which tau pathology correlates more strongly with clinical progression than amyloid-β (Aβ). Zinc (Zn²⁺) is known to promote tau-mediated neurotox...
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder in which tau pathology correlates more strongly with clinical progression than amyloid-β (Aβ). Zinc (Zn²⁺) is known to promote tau-mediated neurotoxicity; however, the underlying mechanisms remain incompletely understood. Our previous work demonstrated that Zinc ions (Zn²⁺) binds to the third microtubule-binding repeat (R3) of tau, inducing oligomerization and enhancing neurotoxicity. Here, we demonstrated that Zn²⁺+R3 elevated phosphorylated tau (p-tau) levels, impaired dendritic spine morphology, reduced synaptophysin expression, and disrupted autophagic flux. Mechanistically, Zn²⁺+R3 was associated with suppression of the Akt/mTOR signaling pathway, concurrent with autophagy initiation and impaired autophagosome-lysosome fusion. However, the present findings are associative in nature, as pharmacological or genetic rescue experiments were not performed; such experiments will be required to formally establish causality. Collectively, these findings suggest that targeting the Zn²⁺ and R3 interaction may represent a potential therapeutic strategy for AD.
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