Brain Res. [JOURNAL]
Sun
200 papers
IGFBP3 and UBE2C are associated with protein modification pathways and serve as prognostic markers in glioma.
Zhou Y, Zhou P
Brain Res · 2026 Jul · PMID 42398694 · Publisher ↗
BACKGROUND: Glioma, the most prevalent malignant primary CNS tumor, features aggressive proliferation and poor prognosis. The prognostic value of core protein modification pathway genes remains unclear. METHODS: Metascap...
BACKGROUND: Glioma, the most prevalent malignant primary CNS tumor, features aggressive proliferation and poor prognosis. The prognostic value of core protein modification pathway genes remains unclear. METHODS: Metascape enrichment identified hub genes in protein modification. IGFBP3 and UBE2C were assessed via Kaplan-Meier, multivariate Cox regression, time-dependent ROC and partial correlation. Promoter methylation (TCGA) and NRI/IDI (CGGA) were analyzed. RESULTS: High IGFBP3 and UBE2C predicted inferior survival across all WHO-grade primary and recurrent gliomas (log-rank P < 0.001). External TCGA validation yielded higher HRs (IGFBP3: N = 697, HR = 3.08; UBE2C: N = 690, HR = 4.58). In CGGA multivariate analysis,adjusted for age, grade and IDH status, IGFBP3 (HR = 2.03) and UBE2C (HR = 2.13) remained independent factors. In the TCGA cohort, time-dependent ROC showed moderate-to-good performance: IGFBP3 AUCs = 0.789 (1y), 0.798 (3y), 0.699 (5y); UBE2C AUCs = 0.784 (1y), 0.838 (3y), 0.808 (5y). Positive co-expression in primary and recurrent gliomas persisted after adjusting for grade, IDH status and 1p/19q codeletion (partial r = 0.138, P = 0.001). Significance held after further adjustment for 1p/19q codeletion and histology (IGFBP3: HR = 1.85; UBE2C: HR = 2.20). NRI and IDI verified incremental predictive value over clinical baselines. UBE2C promoter methylation negatively correlated with expression and differed by IDH status, while IGFBP3 lacked such epigenetic associations. CONCLUSION: IGFBP3 and UBE2C are robust glioma prognostic biomarkers involved in protein modification pathways. Cross-cohort stability and distinct methylation patterns support their use as auxiliary prognostic markers, awaiting prospective validation.
Targeting neurodevelopmental miR132-3p promotes neuroprotection and axon regeneration after optic nerve injury in mice.
D'souza C, Lukomska A, Balaji AJ … +2 more , Brady J, Trakhtenberg EF
Brain Res · 2026 Jul · PMID 42386070 · Publisher ↗
Micro-RNA (miRNA) miR-132 regulates the axonal elongation-to-branching switch in central nervous system (CNS) neurons during maturation, which coincides with the mammalian developmental loss of CNS projection neurons' in...
Micro-RNA (miRNA) miR-132 regulates the axonal elongation-to-branching switch in central nervous system (CNS) neurons during maturation, which coincides with the mammalian developmental loss of CNS projection neurons' intrinsic axon growth capacity. However, it is unknown whether experimental targeting of miR-132 in mature CNS neurons could activate elongation/regeneration of the axons severed by an injury. Here, we characterized miR-132 5p and 3p arm expression during maturation of a prototypical CNS projection neuron, the retinal ganglion cell (RGC), and then tested whether miR-132 arm-specific knockdown (KD) in the RGCs activates elongation/regeneration of axons severed by optic nerve crush (ONC) injury in vivo. We identified the miR132-3p arm as developmentally-upregulated in the RGCs and found that its KD modestly but significantly promoted RGC axon-regeneration and survival. We also gained insights into the miR132-3p KD-regulated biological processes by transcriptomic profiling of the treated injured RGCs, which showed enrichment of a developmental gene network for formation of axonal projections. Thus, neuronal miR132-3p plays a role in axon regeneration after optic nerve injury, and future studies should investigate the underlying mechanisms.
Variability in acoustic startle response and prepulse inhibition across adulthood in Fragile X messenger ribonucleoprotein 1 knockout mice.
Blandin KJ, Douglas L, Lugo JN … +2 more , Thayil JJ, Lugoa JN
Brain Res · 2026 Jul · PMID 42386069 · Publisher ↗
Abstract loading — click title to view on PubMed.
Transcriptome-guided modeling reveals insulin-related metabolic dysfunction in SCA3 mouse cerebellum.
Pan SH, Chang JC, Cheng WL … +2 more , Wei AC, Liu CS
Brain Res · 2026 Jul · PMID 42386068 · Publisher ↗
Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine neurodegenerative disorder in which metabolic involvement may extend beyond proteotoxicity alone. We integrated cerebellar RNA sequencing with transcriptome-constra...
Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine neurodegenerative disorder in which metabolic involvement may extend beyond proteotoxicity alone. We integrated cerebellar RNA sequencing with transcriptome-constrained genome-scale metabolic modeling to characterize metabolic dysregulation in transgenic SCA3 (84Q) versus control (15Q) mice and to relate cerebellar changes to circulating insulin-related measures. Differential expression and preranked gene set enrichment analyses revealed coordinated suppression of insulin/glucose-homeostasis modules and lipid/sterol programs in the SCA3 cerebellum. Context-specific metabolic models derived from iMM1865 and analyzed using parsimonious flux balance analysis, flux variability analysis, and flux sampling indicated reduced oxidative metabolism together with increased nucleotide salvage, one-carbon metabolism, and proteostasis-associated remodeling. Distribution-level comparisons of sampled fluxes detected widespread network reorganization despite modest median shifts. Plasma insulin was elevated in 84Q mice, whereas cerebellar Ins2 and Igf1 transcripts were reduced, consistent with an insulin-related dysregulation signature. Together, these data support broad metabolic reprogramming in the SCA3 cerebellum, including insulin/IGF-related alterations, and nominate pathway-level candidates for future mechanistic validation.
Intranasal stromal cell-derived factor-1α mitigates parkinsonian deficits via dual modulation of neuroinflammation and gut microbiota in MPTP-induced models.
Lian C, Ding N, Xu Z … +11 more , Liao J, Pan L, Lai W, Yang L, Wu S, Zhao G, Zheng D, Ou X, Zheng H, Zhang X, Wang Y
Brain Res · 2026 Jun · PMID 42379412 · Publisher ↗
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and neuroinflammation, with emerging evidence implicating gut-brain axis dysregulation in its pathogenesis....
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and neuroinflammation, with emerging evidence implicating gut-brain axis dysregulation in its pathogenesis. Stromal cell-derived factor-1α (SDF-1α), a chemokine with neuroprotective properties, remains underexplored as a therapeutic agent for PD. This study investigates the efficacy of intranasal SDF-1α administration in mitigating motor deficits, gastrointestinal (GI) dysfunction, and neuroinflammation, and its concurrent effects on the gut microbiota in an MPTP-induced PD mouse model. Male C57BL/6J mice were divided into vehicle, MPTP, and MPTP + SDF-1α groups. Behavioral assessments, including the rotarod test and grip strength test, demonstrated that SDF-1α significantly attenuated MPTP-induced motor impairments, including bradykinesia and coordination deficits. Immunofluorescence analysis revealed that SDF-1α restored tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra (SN), indicating robust dopaminergic neuroprotection. Furthermore, SDF-1α ameliorated GI dysfunction by reducing intestinal permeability, as measured by FITC-dextran assay, and improving gut motility, as assessed by Evans blue transit test. Mechanistically, SDF-1α suppressed nigrostriatal inflammation by reducing pro-inflammatory cytokines (IL-6, TNF-α) while elevating anti-inflammatory markers (IL-4, IL-10). Activation of astrocytes (GFAP+) in MPTP-treated mice was reduced to near-control levels following SDF-1α administration. Gut microbiota analysis via 16S rRNA sequencing revealed that SDF-1α restored both α- and β-diversity, counteracting MPTP-induced dysbiosis. Notably, SDF-1α reversed the depletion of Akkermansia, a keystone genus associated with mucosal integrity and barrier function. These findings demonstrate that intranasal SDF-1α concurrently attenuates motor and gastrointestinal deficits, nigrostriatal neuroinflammation, intestinal barrier disruption, and gut microbiota dysbiosis in the MPTP mouse model. Our study highlights the microbiota-gut-brain axis as a critical therapeutic target in PD and proposes intranasal SDF-1α delivery as a novel, non-invasive strategy warranting further mechanistic investigation.
Emotions, the amygdala, and the right hemisphere.
Gainotti G
Brain Res · 2026 Jun · PMID 42364889 · Publisher ↗
No effort has still been made to integrate within a general model of emotions the relations between amygdala, fear (and other emotions) and the right hemisphere. This integration is the aim of this review that will start...
No effort has still been made to integrate within a general model of emotions the relations between amygdala, fear (and other emotions) and the right hemisphere. This integration is the aim of this review that will start with the description of a model viewing emotions as a primitive adaptive system, alternative to the cognitive system. I will then analyze the main characteristics of the amygdala and of its subcortical pathway that allows to detect, with an urgency procedure, life-threatening stimuli, and to provide, with automatic and unconscious processing modalities, rough sensory data to the amygdala. Since this subcortical pathway is lateralized to the right hemisphere in humans, but not in animals, the reasons of this evolution will be discussed with reference to the "crowding model" , which assumes that brain lateralization may serve to avoid conflicts between systems (such as the emotional and the cognitive ones) competing at the decisional level. This model could explain the left lateralization of language and the consequent complex renovation of the working modalities of both hemispheres. Support to this model comes from the observation that the right hemisphere is characterized not only by a greater representation of emotions, but also by automatic and unconscious processing modalities typical of the emotional system, whereas the left hemisphere is characterized by language-mediated conscious and intentional functioning modalities.
Electroacupuncture treatment enhances hippocampal growth hormone level and restores mitochondrial function in vascular dementia rats.
Liu C, Dong X, Yin H … +4 more , Chen X, Zhen Y, Zhu G, Wang J
Brain Res · 2026 Oct · PMID 42361950 · Publisher ↗
Although electroacupuncture (EA) yields favorable clinical outcomes for vascular dementia (VD), its mechanisms remain poorly understood. This study aimed to investigate the protective effects of EA on VD by regulating gr...
Although electroacupuncture (EA) yields favorable clinical outcomes for vascular dementia (VD), its mechanisms remain poorly understood. This study aimed to investigate the protective effects of EA on VD by regulating growth hormone (GH). A rat VD model was induced by multiple microinfarction (MMI). EA was applied at Baihui (GV20) and Shenting (GV24), and its effects on cognitive function and synaptic lesions were assessed. Hippocampal synaptic morphology and synaptic protein expression, as well as GH level were detected using transmission electron microscopy and biochemical methods. Finally, GH and PGC-1α agonists were used for mechanistic validation. Our results showed that MMI rats presented severe cognitive deficits and synaptic dysfunction relative to sham rats, and EA successfully alleviated these abnormalities. The expression of GH-related and mitochondrial proteins in the hippocampus continuously decreased on D7, D14 and D21 post-modeling, and EA significantly prevented such reductions. EA also increased hippocampal GH level and repaired damaged mitochondria in VD rats. Of note, GH receptor and PGC-1α agonists exerted similar beneficial effects as EA, validating the proposed mechanism. Collectively, EA at GV20 and GV24 increases hippocampal GH levels, rescues mitochondrial and synaptic dysfunction in VD rats, and possesses great potential for clinical application.
Effects of transcutaneous auricular nerve stimulation on thalamic relay: A randomized brain imaging study in chronic low back pain patients.
Wu Y, Kong Q, Sacca V … +4 more , Reddy S, Hodges S, Li Y, Kong J
Brain Res · 2026 Jun · PMID 42361949 · Publisher ↗
Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potential therapeutic option for chronic pain. This study investigates the modulatory effects of taVNS and transcutaneous greater auricular nerve...
Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potential therapeutic option for chronic pain. This study investigates the modulatory effects of taVNS and transcutaneous greater auricular nerve stimulation (tGANS) on thalamocortical circuits. Seventy individuals with chronic low back pain (cLBP) were randomized to receive four weeks of taVNS or tGANS. Structural and resting-state functional MRI data were acquired at baseline and post-treatment. Seed-based functional connectivity analysis was performed using the ventral posterolateral (VPL) and mediodorsal (MD) thalamic nuclei as seeds. Additionally, gray matter (GM) analysis and diffusion tensor imaging (DTI) fiber tracking were conducted to assess structural changes. 51 patients (taVNS: n = 25, tGANS: n = 26) completed the study. Both groups showed significant reductions in pain intensity, bothersomeness, and interference scores, with no significant between-group differences. Both interventions modulated static and dynamic functional connectivity (sFC/dFC) within thalamocortical, limbic, and sensorimotor networks. In the taVNS group, there were significant decreases in both the sFC and fiber integrity between the MD and the left postcentral gyrus, and the gray matter volume of the left postcentral gyrus after taVNS treatment. Additionally, taVNS reduced the dFC between the VPL and the postcentral gyrus, which correlated with decreased pain intensity. Our findings suggest that both taVNS and tGANS mitigate cLBP and modulate thalamocortical connectivity. Elucidating their distinct mechanisms may advance the development of new strategies for chronic pain management.
Adaptive reconfiguration of prefrontal networks during prolonged cognitive interference: Evidence from fNIRS.
Pan Y, Peng J, Li X … +3 more , Jin X, Yun L, Chen Z
Brain Res · 2026 Oct · PMID 42349602 · Publisher ↗
In the era of information overload, understanding the brain's adaptive responses to prolonged cognitive tasks is critical. This study investigates the neural compensatory mechanisms that sustain cognitive performance und...
In the era of information overload, understanding the brain's adaptive responses to prolonged cognitive tasks is critical. This study investigates the neural compensatory mechanisms that sustain cognitive performance under mental fatigue, offering insights into dynamic resource allocation and practical applications in high-demand settings. Twenty healthy participants performed a Stroop-based cognitive interference task while prefrontal hemodynamic activity was monitored using functional near-infrared spectroscopy (fNIRS). Subjective fatigue was assessed via the Multidimensional Fatigue Inventory (MFI-20), NASA Task Load Index (NASA-TLX), and Visual Analogue Scale (VAS). Behavioral performance (reaction time and accuracy) was recorded simultaneously. Neural activation was analyzed using a Generalized Linear Model (GLM), and functional connectivity alongside network topology metrics (global efficiency, clustering coefficient) were evaluated. Results show that subjective fatigue increased significantly post-task (MFI-20, p < 0.05), with progressive rise in VAS scores. Behaviorally, reaction times decreased while accuracy remained stable, indicating a speed-accuracy trade-off. fNIRS revealed marked activation changes in specific prefrontal regions (e.g., CH1, CH7), with overall activation shifting from positive to negative. This pattern may reflect time-dependent modulation of task-evoked activation and could be associated with multiple factors, including fatigue-related changes in engagement, habituation effects, or resource-related processes. In addition, fatigue accumulation was accompanied by increased functional connectivity between the frontal eye fields (FEF) and dorsolateral prefrontal cortex (DLPFC) (F = 4.61, p = 0.008), as well as between the frontopolar area (FPA) and DLPFC (F = 3.74, p = 0.020). Global efficiency (F = 0.169, p = 0.022) and clustering coefficient (F = 0.177, p = 0.008) also showed significant increases across task progression.Together, these findings may indicate time-dependent modulation of prefrontal network organization during prolonged cognitive interference tasks. Rather than reflecting a single mechanism, these changes could be associated with dynamic adjustments in functional coordination under sustained task demands. The present findings may provide preliminary neurophysiological evidence relevant to neuroergonomics, brain-computer interfaces, and cognitive workload management.
Horizontal image compression significantly impairs human face identity recognition.
Venetis A, Rossion B
Brain Res · 2026 Oct · PMID 42349601 · Publisher ↗
Face identity recognition (FIR) is a key function for human social interactions, supported by specialized neural mechanisms. Previous studies have reported remarkable resilience of FIR to large vertical (i.e., top to bot...
Face identity recognition (FIR) is a key function for human social interactions, supported by specialized neural mechanisms. Previous studies have reported remarkable resilience of FIR to large vertical (i.e., top to bottom) or horizontal (i.e., ear-to-ear) compression of images, generally taken as evidence that spatial (configural) cues may play a limited role in this function. However, resistance of FIR to single-axis image compression rests on limited evidence, i.e., behavioral accuracy rates obtained with repeated iconic familiar face images presented for extended response windows. Here we objectively quantify the impact of single-axis image compression on implicit neural markers of single glance FIR. Twenty-one participants were tested in a well-validated paradigm, viewing the same unfamiliar face presented 6 times per second at one of five horizontal compression levels (0%, 22%, 45%, 67%, 90%), with various identity changes occurring periodically every five faces. Robust electroencephalographic (EEG) FIR responses observed over the occipito-temporal cortex at 1.2 Hz harmonics were fully preserved at a low compression level (22%) but sharply declined with increasing compression levels, showing 40% amplitude reduction at 2/3 image compression and near-complete suppression at 90%. These observations provide original evidence against a widespread view that single-axis, in particular horizontal, image compression has little effect on human FIR. Impairment of FIR with horizontal image compression can be attributed to distortion of relative distances between features, but also to the shape of local features and of the overall face structure.
Altered theta-band sensory gating in individuals with high sensory processing sensitivity (SPS).
Lin BL, Chiu CC, Huang CM … +2 more , Lu H, Cheng CH
Brain Res · 2026 Oct · PMID 42342099 · Publisher ↗
Sensory processing sensitivity (SPS) is a personality trait characterized by heightened responsiveness to environmental stimuli, yet its neurophysiological mechanisms remain unclear. Sensory gating (SG), an inhibitory pr...
Sensory processing sensitivity (SPS) is a personality trait characterized by heightened responsiveness to environmental stimuli, yet its neurophysiological mechanisms remain unclear. Sensory gating (SG), an inhibitory process that suppresses redundant or irrelevant sensory inputs, is often assessed through event-related potentials (ERPs) but may also rely on non-phase-locked oscillatory activity. The present study examined SG in individuals with high versus low SPS using both time-domain and time-frequency electrophysiological measures while strictly controlling for serotonin transporter polymorphism (5-HTTLPR). From an initial cohort of 518 adults, participants in the top and bottom 10 % of Highly Sensitive Person (HSP) Scale scores who were homozygous for the S allele (SS genotype) completed a paired-stimulus auditory SG paradigm (26 high SPS; 25 low SPS). Time-domain analyses showed no group differences in SG ratios or SG differences of the N100 component. In contrast, time-frequency analyses revealed that individuals with high SPS exhibited significantly stronger gating in theta oscillations compared to low-SPS individuals (false discovery rate corrected p < 0.05). These findings suggest that SPS is not characterized by uniformly weaker sensory inhibition, but rather by altered oscillatory sensory-gating dynamics during repetitive sensory processing. In conclusion, theta-band SG may represent a candidate electrophysiological correlate of SPS and highlights the potential value of oscillatory measures for understanding individual differences in sensory responsiveness.
Mice with Sox5 inactivation in the Emx1 lineage as a model for the human Lamb-Shaffer neurodevelopmental syndrome.
Ferrari EK, Dong J, Duncan-Field K … +5 more , Sharma V, Whipple S, McCoy AJ, Marsh ED, Lefebvre V
Brain Res · 2026 Oct · PMID 42336027 · Publisher ↗
Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder caused by variants that inactivate one SOX5 allele and thus reveal human SOX5 haploinsufficiency in higher-order brain functions. SOX5 encodes an SRY-relate...
Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder caused by variants that inactivate one SOX5 allele and thus reveal human SOX5 haploinsufficiency in higher-order brain functions. SOX5 encodes an SRY-related transcription factor highly expressed in cortical deep-layer excitatory neurons. Sox5 mice were previously shown to die at birth with severely impaired differentiation of these cells, whereas Sox5 mice appeared normal throughout life but were not investigated for neurological defects. We here asked whether these mice and mice with Emx1-mediated inactivation of Sox5 in the progenitors of cortical and hippocampal excitatory neurons and glia exhibited LAMSHF-like behaviors. Neocortical neuron defects were equally severe in Sox5 and Sox5Emx1 mice and were marginal in Sox5 and Sox5Emx1 mice. Sox5Emx1 mice survived birth but failed to thrive around weaning, unless given a nutritious gel complement. Behavior tests revealed motor performance deficits, reduced anxiety, impaired learning and memory skills, and autistic-like behaviors in Sox5Emx1 mice and minor changes in Sox5 and Sox5Emx1 mice. Electroencephalography findings were consistent with a mild, diffuse alteration of the cortex organization in homozygous mutants. Thus, while the abnormal features of Sox5Emx1 mice evoked LAMSHF, global and conditional heterozygous mutants exhibited mild or no deficiencies. We conclude that mouse Sox5 may not be as haploinsufficient as human SOX5 in facilitating achievement of higher-order functions and that mice with homozygous loss of Sox5 in the Emx1 lineage are a suitable model to further investigate the LAMSHF-related functions of SOX5 and to preclinically test candidate therapies for LAMSHF individuals.
Network pharmacology and transcriptomic analysis reveal wogonin as a key bioactive compound of Scutellaria baicalensis Georgi in suppressing glioma progression via PI3K-Akt pathway suppression.
Jia M, Liu F, Li J … +6 more , Feng X, Ma X, Zhang R, Zhang W, Liu G, Liu H
Brain Res · 2026 Oct · PMID 42336026 · Publisher ↗
OBJECTIVE: Glioblastoma (GBM) remains one of the most lethal brain tumors due to pronounced heterogeneity and persistent activation of oncogenic signaling. This study aimed to identify bioactive constituents of Scutellar...
OBJECTIVE: Glioblastoma (GBM) remains one of the most lethal brain tumors due to pronounced heterogeneity and persistent activation of oncogenic signaling. This study aimed to identify bioactive constituents of Scutellaria baicalensis Georgi (SBG) with anti-GBM potential and to elucidate their molecular mechanisms. METHODS: An integrated multi-layered strategy combining network pharmacology, molecular docking, molecular dynamics simulations, transcriptomic profiling, and in vitro functional assays was employed. Wogonin, a top-ranked SBG-derived flavonoid, was selected for experimental validation. Functional and mechanistic studies were primarily conducted in U251 cells, including proliferation, migration, clonogenicity, cell-cycle distribution, apoptosis, and pathway interrogation. U87MG cells were used as an independent validation model. Sub-cytotoxic concentrations were applied to distinguish specific anti-migratory effects from general cytotoxicity. Rescue experiments using the AKT activator SC79 were performed to establish mechanistic causality. Clinical relevance was assessed using TCGA‑GBM transcriptomic datasets. RESULTS: Network pharmacology analysis identified 32 active SBG compounds targeting 362 GBM-associated proteins, with enrichment in the PI3K-Akt signaling pathway. Functional screening demonstrated that wogonin exhibited the most potent anti-GBM activity among candidate compounds. In U251 cells, wogonin significantly suppressed proliferation, migration, and clonogenicity, induced G2/M cell-cycle arrest, and promoted apoptosis. Transcriptomic profiling revealed extensive gene expression reprogramming, with coordinated downregulation of PI3K-Akt pathway components, which was further confirmed by reduced phosphorylation of PI3K and AKT. Importantly, these effects were partially reversed by SC79-mediated AKT activation, establishing a causal role of AKT inhibition in wogonin-induced phenotypes. Low-dose assays demonstrated that wogonin inhibited migration under sub-cytotoxic conditions, excluding non-specific cytotoxicity as the primary driver. These findings were further validated in U87MG cells, confirming the reproducibility of both phenotypic and mechanistic effects across GBM models. Molecular docking and molecular dynamics simulations supported stable binding of wogonin to AKT1 and PIK3CA, providing mechanistic plausibility for the observed pathway inhibition. TCGA‑GBM analysis identified AKT1 as a clinically relevant prognostic factor. CONCLUSION: This study demonstrates that wogonin acts as a key bioactive constituent of SBG and suppresses GBM progression through AKT1-centered PI3K-Akt pathway inhibition, with rescue experiments supporting a causal contribution of AKT suppression to the observed phenotypes. By integrating multi-omics analysis with functional and rescue-based validation, this work provides mechanistic evidence supporting wogonin as a promising compound for further preclinical evaluation in GBM.
Interactions between aging and white matter hyperintensities-defined cerebral small vessel disease on prefrontal cortex metabolism: a comprehensive F-FDG-PET/MRI analysis.
Lu JJ, Ma J, Xiang YT … +5 more , Wu JJ, Zheng MX, Li LL, Hua XY, Xu JG
Brain Res · 2026 Oct · PMID 42331270 · Publisher ↗
Metabolic disruption in the prefrontal cortex is closely associated with functional decline in cerebral small vessel disease (CSVD), especially among older adults. This study aimed to investigate both the separate and co...
Metabolic disruption in the prefrontal cortex is closely associated with functional decline in cerebral small vessel disease (CSVD), especially among older adults. This study aimed to investigate both the separate and combined effects of aging and CSVD on prefrontal cortex metabolism. A total of 191 participants who underwent F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging scanning were divided into four groups: middle-aged healthy control (HC) (n = 60), middle-aged CSVD patients (n = 52), older HC (n = 35) and older CSVD patients (n = 44). Age was categorized as middle-aged (40-59 years) and older (60-80 years), and enrolled CSVD cases were strictly diagnosed as white matter hyperintensities (WMH)-defined CSVD following standardized criteria. Main and interaction effects of aging and CSVD on prefrontal cortex metabolism were analyzed across three levels: local region, connectivity, and network, with multiple comparison correction applied. Significant interactions between aging and CSVD were identified in the relative mean standardized uptake value of the prefrontal cortex, as well as in global (clustering coefficient) and nodal properties (nodal clustering coefficient, nodal efficiency, and nodal local efficiency). Additionally, significant main effects of age and CSVD were observed on the prefrontal cortex' average standardized uptake value, whereas main effects of age were found on both global and nodal properties of the prefrontal metabolic network. These findings demonstrate altered prefrontal metabolic profiles associated with aging and WMH-defined CSVD. These observed metabolic patterns offer preliminary insights, and may guide future studies integrating comprehensive clinical assessments and longitudinal follow-up.
Circulating acidic α-glucosidase as a potential biomarker for lactate-related immunometabolism in ischemic stroke.
Liao D, Zeng T, Zhang M … +9 more , Yang Q, Gao C, Gao Z, Bai J, Jin L, Wang H, Luo P, Dai S, Li X
Brain Res · 2026 Oct · PMID 42323125 · Publisher ↗
BACKGROUND: The role of lactate metabolism in ischemic stroke (IS) remains incompletely understood. This study aimed to characterize lactate-related transcriptomic profiles in IS to identify novel diagnostic biomarkers....
BACKGROUND: The role of lactate metabolism in ischemic stroke (IS) remains incompletely understood. This study aimed to characterize lactate-related transcriptomic profiles in IS to identify novel diagnostic biomarkers. METHODS: Gene co-expression network analysis and machine learning were used to identify core lactate metabolism-related genes from public transcriptomic datasets and validate them in an independent clinical cohort. Single-cell mouse brain transcriptomic data further characterized GAA expression across brain cell types. An in vitro OGD/R model was established in GAA-high-expressing cells to assess its expression under ischemic/hypoxic conditions. GAA expression in immune cells and its association with macrophage polarization were also evaluated. RESULTS: GAA emerged as a core gene, exhibiting significant upregulation in the whole blood of IS patients with robust diagnostic performance (area under the curve = 0.873). This upregulation was confirmed in validation models. After stroke, GAA exhibited a cell-type-specific expression pattern: it was elevated in macrophages and microglia. Notably, GAA expression positively correlated with the anti-inflammatory M2 macrophage marker MRC1 (r = 0.43) and negatively correlated with the pro-inflammatory cytokine interleukin-1β (IL-1β) (r = -0.48), indicating that high GAA levels favor M2-biased polarization. CONCLUSION: GAA acts as a potential upstream regulator of lactate metabolism in IS. By linking lysosomal glycogen metabolism to lactate production, GAA may modulate macrophage polarization via a "lactate timer" mechanism. These findings highlight GAA as a promising blood-based biomarker for the auxiliary diagnosis of IS.
Predictive value of serum miR‑670‑3p for post‑stroke cognitive impairment in aging patients with acute ischemic stroke.
Shen J, Yang N, Zhao M … +2 more , Feng J, Li W
Brain Res · 2026 Jun · PMID 42323124 · Publisher ↗
BACKGROUND: Post-stroke cognitive impairment (PSCI) is a frequent and severe complication that commonly occurs in aging patients with acute ischemic stroke (AIS). AIMS: To investigate serum miR-670-3p expression in aging...
BACKGROUND: Post-stroke cognitive impairment (PSCI) is a frequent and severe complication that commonly occurs in aging patients with acute ischemic stroke (AIS). AIMS: To investigate serum miR-670-3p expression in aging AIS patients and evaluate its predictive performance for PSCI, and to explore the underlying mechanism. METHODS: A total of 115 aging patients with AIS and 60 age- and sex-matched healthy volunteers were enrolled in this study. All AIS patients were to divide them into PSCI and non-PSCI groups. RT-qPCR was applied to measure the expression levels of serum miR-670-3p and HMGB1 mRNA. ROC curve and logistic regression analyses were conducted to assess the predictive value of miR-670-3p for PSCI. For in vitro assays, SH-SY5Y cells were utilized to establish an OGD/R model, which mimics cerebral ischemia-reperfusion injury. RESULTS: Serum miR-670-3p was significantly decreased in AIS, especially in patients with PSCI. miR-670-3p was significantly correlated with NIHSS, MoCA and MMSE scores, with an AUC value of 0.842 for predicting post-stroke cognitive impairment, and served as an influencing factor. In vitro experiments revealed that miR-670-3p directly targeted HMGB1 and relieved neuronal injury, oxidative stress and inflammation induced by oxygen-glucose deprivation/reperfusion. CONCLUSIONS: Serum miR-670-3p serves as a promising non-invasive predictive biomarker for PSCI in aging AIS patients. miR-670-3p/HMGB1 axis may serve as a new potential therapeutic target for cognitive impairment secondary to ischemic stroke.
Progressive orexin A positive neuron loss in the 6-OHDA mouse model of Parkinson's disease: a pilot study with validation of an orexin A immunohistochemistry protocol for paraffin-embedded tissue.
Braun A, Vo PT, Bobrovskaya L
Brain Res · 2026 Oct · PMID 42323123 · Publisher ↗
The aim of this pilot study was to assess a time-dependent loss of orexin neurons in the unilateral intrastriatal 6-OHDA mouse model and to optimise the immunohistochemistry protocol for formalin-fixed, paraffin-embedded...
The aim of this pilot study was to assess a time-dependent loss of orexin neurons in the unilateral intrastriatal 6-OHDA mouse model and to optimise the immunohistochemistry protocol for formalin-fixed, paraffin-embedded mouse brain tissue. A progressive loss of orexin A positive neurons in the lateral hypothalamus was observed in the lesioned side relative to the non-lesioned side. A significant reduction of orexin A positive neurons in the lateral hypothalamus was observed at 4 weeks with further loss at 6-8 weeks post 6-OHDA induction. Orexin neuron loss in the lateral hypothalamus has been reported in post-mortem Parkinson's disease patients and multiple animal studies, particularly in rats; however, evidence in neurotoxic mouse models remains limited. Orexin A positive neuron loss occurred alongside transient motor deficits, olfactory impairments, subtle cognitive changes and gastrointestinal dysfunction. Additionally, an orexin A immunohistochemistry protocol was successfully established for formalin-fixed, paraffin-embedded mouse brain tissue, enabling reproducible and reliable detection of orexin neurons as an alternative to frozen sections. This pilot study serves as a proof of concept that the unilateral intrastriatal 6-OHDA mouse model can successfully recapitulate the progressive loss of orexin A positive neurons and validates this model's suitably for investigating the longitudinal mechanisms of PD symptoms and pathology.
Retraction notice to "Down-regulation of Nogo receptor promotes functional recovery by enhancing axonal connectivity after experimental stroke in rats" [Brain Res. 1360 (2010) 147-158].
Wang T, Wang J, Yin C … +3 more , Liu R, Zhang JH, Qin X
Brain Res · 2026 Oct · PMID 42321056 · Publisher ↗
Abstract loading — click title to view on PubMed.
Duration-dependent effects of sucrose intake on fear extinction via distinct mechanisms in the amygdala and hippocampus.
He M, Huang J, Zhang T … +6 more , Lin S, Tong Y, Zhu H, Wu Y, Song W, Shen X
Brain Res · 2026 Oct · PMID 42320786 · Publisher ↗
Dietary sugar intake has been increasingly linked to emotional cognition and mental health. However, the duration-dependent effects of sugar intake on fear memory extinction remain elusive. In this study, we found that l...
Dietary sugar intake has been increasingly linked to emotional cognition and mental health. However, the duration-dependent effects of sugar intake on fear memory extinction remain elusive. In this study, we found that long-term sucrose intake impaired fear memory extinction, while short-term sucrose exposure facilitated fear memory extinction. Moreover, long-term sucrose consumption induced aberrant activation of neurons and astrocytes in the basolateral amygdala (BLA), which was characterized by upregulation of proenkephalin (Penk) in engram neurons alongside increased insulin-like growth factor binding protein 2 (Igfbp2) in astrocytes, indicating that a sustained co-activation may stabilize extinction-resistant fear circuits. In contrast, short-term sucrose intake did not activate the amygdala or prefrontal cortex but induced increased hippocampal insulin expression. Pharmacological blockade of hippocampal insulin receptors abolished the behavioral effect of short-term sucrose exposure, supporting a functional contribution of hippocampal insulin signaling. Overall, these findings demonstrate that the effects of sugar on fear extinction depend strongly on the duration of exposure via distinct mechanisms, providing a novel insight into how eating habits influence emotional cognition and mental health.
Amyloid-β1-42 oligomers compromise oligodendrocyte precursor cells and disrupt blood-brain barrier integrity in vitro.
Toyokawa M, Yasuda K, Kikuya A … +12 more , Asada-Utsugi M, Hida M, Nakamura Y, Yanagida N, Toda S, Kaji S, Kinoshita Y, Ono Y, Takahashi R, Matsumoto R, Kinosita A, Maki T
Brain Res · 2026 Oct · PMID 42320785 · Publisher ↗
Amyloid-β (Aβ), particularly the aggregation-prone Aβ1-42, plays a central role in Alzheimer's disease (AD). While its neuronal toxicity is well known, effects on glial and vascular cells remain unclear. To investigate h...
Amyloid-β (Aβ), particularly the aggregation-prone Aβ1-42, plays a central role in Alzheimer's disease (AD). While its neuronal toxicity is well known, effects on glial and vascular cells remain unclear. To investigate how Aβ1-42 oligomers affect oligodendrocyte precursor cells (OPCs), pericytes (PCs), and endothelial cells (ECs), and how these effects contribute to blood-brain barrier (BBB) dysfunction. In vitro assays were used to assess cell viability and BBB integrity following Aβ exposure. Transcriptomic profiling was performed on Aβ1-42-treated OPCs. Transendothelial electrical resistance (TEER) was used to measure barrier function. Aβ1-42, but not Aβ1-40, induced cytotoxicity in OPCs and PCs. ECs showed impaired barrier function without cell death. Aβ1-42-treated OPCs upregulated pro-inflammatory genes (Mmp9, Il1b) and downregulated genes related to cell cycle and growth signaling. Conditioned media from Aβ-exposed OPCs and PCs reduced TEER in ECs, indicating paracrine-mediated BBB disruption. These findings demonstrate that Aβ1-42 oligomers impair BBB integrity under in vitro conditions through both direct and non-cell autonomous mechanisms. Further in vivo studies are warranted to validate the relevance of these mechanisms in AD pathogenesis.
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