Brain Research Bulletin最新文献_第7页

DHX9 aggravates epilepsy by promoting STAT1 phosphorylation to increase oxidative stress and apoptosis DHX9通过促进STAT1磷酸化增加氧化应激和细胞凋亡而加重癫痫。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-01 DOI: 10.1016/j.brainresbull.2025.111650

Hong Chen , Qiannan Song , Da-Qing Feng

Background

DEAH-box helicase 9 (DHX9), as a member of the RNA helicase family, plays important roles in various diseases, but its specific function and molecular mechanisms in epilepsy remain unclear. This study aims to investigate the role of DHX9 in epilepsy and its interaction mechanisms with STAT1.

Methods

Acute and chronic epilepsy mouse models induced by pentylenetetrazole (PTZ) and kainic acid (KA)-induced epilepsy mouse models were established to detect DHX9 expression levels in hippocampal tissue. In vitro epilepsy models were established using HT22 mouse hippocampal neuronal cell lines and BV2 microglial cell lines to analyze DHX9 expression changes. Co-immunoprecipitation was employed to detect protein-protein interactions between DHX9 and STAT1. STAT1-specific inhibitors were used in rescue experiments to validate the critical role of STAT1 in DHX9-mediated pathogenic effects. Western blot and immunofluorescence staining were used to detect oxidative stress markers and apoptosis-related indicators.

Results

DHX9 expression was upregulated in hippocampal tissue from PTZ-induced acute and chronic epilepsy mice and KA-induced epilepsy mice. In vitro experiments confirmed that DHX9 expression was similarly increased in epilepsy models constructed with HT22 neurons and BV2 microglia. Functional studies demonstrated that DHX9 overexpression aggravated neuronal injury, including increased apoptosis rate, elevated oxidative stress levels, and promoted inflammatory responses. Conversely, silencing DHX9 through shRNA reduced neuronal injury in KA-induced epilepsy mouse models. Mechanistic studies revealed that DHX9 silencing exerted neuroprotective effects by inhibiting the STAT1 signaling pathway, reducing oxidative stress and apoptosis. Co-immunoprecipitation experiments confirmed direct protein-protein interactions between DHX9 and STAT1. Rescue experiments further demonstrated that STAT1-specific inhibitors could reverse DHX9 overexpression-induced neuronal injury, proving that STAT1 is a key downstream molecule mediating DHX9's pathogenic effects.

Conclusion

This study reveals the important role of DHX9 in epilepsy pathogenesis and elucidates the molecular mechanism by which DHX9 directly interacts with STAT1 and promotes its phosphorylation, thereby activating downstream oxidative stress and apoptotic signaling pathways, ultimately aggravating epileptic neuronal injury.

背景：DEAH-box解旋酶9 （DHX9）作为RNA解旋酶家族的一员，在多种疾病中发挥重要作用，但其在癫痫中的具体功能和分子机制尚不清楚。本研究旨在探讨DHX9在癫痫中的作用及其与STAT1的相互作用机制。方法：建立戊四唑（PTZ）诱导的急、慢性癫痫小鼠模型和kainic acid （KA）诱导的癫痫小鼠模型，检测海马组织中DHX9的表达水平。采用HT22小鼠海马神经元细胞系和BV2小胶质细胞系建立体外癫痫模型，分析DHX9表达变化。采用免疫共沉淀法检测DHX9与STAT1之间的蛋白相互作用。在救援实验中使用STAT1特异性抑制剂来验证STAT1在dhx9介导的致病作用中的关键作用。Western blot和免疫荧光染色检测氧化应激标志物和细胞凋亡相关指标。结果：ptz诱导的急、慢性癫痫小鼠和ka诱导的癫痫小鼠海马组织中DHX9表达上调。体外实验证实，DHX9在HT22神经元和BV2小胶质细胞构建的癫痫模型中表达同样增加。功能研究表明，DHX9过表达加重了神经元损伤，包括细胞凋亡率升高、氧化应激水平升高、炎症反应增强。相反，通过shRNA沉默DHX9可减少ka诱导癫痫小鼠模型中的神经元损伤。机制研究表明，DHX9沉默通过抑制STAT1信号通路、减少氧化应激和细胞凋亡发挥神经保护作用。共免疫沉淀实验证实了DHX9与STAT1之间的直接蛋白蛋白相互作用。救援实验进一步证实，STAT1特异性抑制剂可逆转DHX9过表达诱导的神经元损伤，证明STAT1是介导DHX9致病作用的关键下游分子。结论：本研究揭示了DHX9在癫痫发病中的重要作用，阐明了DHX9直接与STAT1相互作用，促进其磷酸化，进而激活下游氧化应激和凋亡信号通路，最终加重癫痫神经元损伤的分子机制。

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引用次数: 0

Prefrontal neurophysiological changes associated with subanesthetic esketamine accelerating mice emergence from propofol anesthesia 亚麻醉艾氯胺酮加速异丙酚麻醉小鼠苏醒相关的前额叶神经生理变化。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-01 DOI: 10.1016/j.brainresbull.2025.111648

Yinying Sun , Bo Li , Yiting Wang , Xuliang Jiang , Su Tang , Jiayi Zhang , Jun Zhang

Background

Recent studies have demonstrated that subanesthetic dose of ketamine or its S-enantiomer, esketamine, can paradoxically accelerate the recovery of consciousness in rodents following general anesthesia. However, the neural mechanisms underlying this "awakening-promoting" effect remain poorly understood.

Methods

Adult C57BL/6 J mice were anesthetized with propofol, 0and a low dose of esketamine (2 mg/kg) was administered intravenously to assess its awakening effects through behavioral tests. In vivo multichannel electrophysiological recordings, calcium imaging, and two-photon imaging combined with neurotransmitter probes targeting 5-hydroxytryptamine(5-HT) and acetylcholine (ACh) were employed to investigate electrophysiological and neurochemical dynamics in the prefrontal cortex (PFC) during the awakening process.

Results

Subanesthetic esketamine significantly accelerated awakening from propofol anesthesia in mice. In the PFC, esketamine hastened the emergence of γ oscillations and triggered earlier activation of neuronal somata and dendrites in layer V, while delaying activation in layer II/III neurons. Additionally, subanesthetic esketamine induced inter-layer phase desynchronization and a premature increase in ACh and 5-HT levels in the PFC during the awakening process.

Conclusion

Our findings suggest that low-dose esketamine facilitates mice awakening from propofol anesthesia may by orchestrating a sequence of neural events in the PFC. This study provides novel mechanistic insight into the paradoxical emergence from anesthesia induced by subanesthetic esketamine/ketamine.

背景：最近的研究表明，亚麻醉剂量的氯胺酮或其s -对体艾氯胺酮可以矛盾地加速啮齿动物全身麻醉后的意识恢复。然而，这种“唤醒促进”效应背后的神经机制仍然知之甚少。方法：用异丙酚麻醉C57BL/6J成年小鼠，并静脉注射小剂量艾氯胺酮（2mg/kg），通过行为学试验评价其唤醒作用。采用体内多通道电生理记录、钙成像和双光子成像结合靶向5-羟色胺（5-HT）和乙酰胆碱（ACh）的神经递质探针，研究了觉醒过程中前额叶皮层（PFC）的电生理和神经化学动力学。结果：亚麻醉艾氯胺酮显著加速异丙酚麻醉小鼠苏醒。在PFC中，艾氯胺酮加速了γ振荡的出现，并触发了V层神经元体和树突的早期激活，而延迟了II/III层神经元的激活。此外，亚麻醉艾氯胺酮诱导觉醒过程中PFC的层间相不同步和乙酰胆碱和5-羟色胺水平的过早增加。结论：我们的研究结果表明，低剂量艾氯胺酮可能通过在pfc中安排一系列神经事件来促进小鼠从异丙酚麻醉中醒来。这项研究为亚麻醉艾氯胺酮/氯胺酮诱导的麻醉中出现的矛盾提供了新的机制见解。

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引用次数: 0

ATF3 promotes ferroptosis by transcriptional repression of SLC7A11 in ischemic stroke 缺血性卒中中ATF3通过抑制SLC7A11的转录促进铁下垂

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-01 DOI: 10.1016/j.brainresbull.2025.111659

Ying He , Ying Zhao , Ruitao Mao , Wangxiang Li , Tengmin Gui , Huanhuan Ren , Shuxian Zhang , Yuan Song , Liqing Yao

Activating transcription factor 3 (ATF3) and solute carrier family 7 member 11 (SLC7A11) have been implicated in ferroptosis following ischemic stroke. However, the precise regulatory mechanisms between ATF3 and SLC7A11 remain incompletely understood. This study aims to investigate the regulatory mechanism of ATF3 and SLC7A11 in ferroptosis during ischemic stroke. The stroke-related microarray dataset GSE58294 was downloaded from the GEO database. Differential gene expression analysis was performed to identify ferroptosis-related differentially expressed genes (FRDEGs). Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction, were conducted. Key hub genes were validated in both a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R) using BV2 microglia. Cell viability was assessed by CCK-8 assay. Ferroptosis-related proteins were analyzed by Western blot, and apoptosis was detected by flow cytometry. Levels of reactive oxygen species (ROS) and Fe²⁺ were measured using immunofluorescence and ELISA, respectively. Bioinformatic analysis identified SLC7A11 as a significantly altered gene in stroke. The PPI network predicted ATF3 as a key transcription factor regulating SLC7A11. In vitro, transfection with si-ATF3 downregulated GPX4 and FTH1 levels while upregulating IREB2 and ALOX15. Furthermore, si-ATF3 transfection reduced ROS levels and iron concentration in microglia, effects that were reversed by the ferroptosis inducer erastin. Notably, SLC7A11 expression was significantly increased following ATF3 knockdown. Our findings demonstrate that ATF3 preliminarily promotes ferroptosis by binding to the SLC7A11 promoter and inhibiting its expression, providing a novel mechanistic insight into ischemic stroke pathology.

激活转录因子3 （ATF3）和溶质载体家族7成员11 （SLC7A11）与缺血性卒中后铁下垂有关。然而，ATF3和SLC7A11之间的精确调控机制仍然不完全清楚。本研究旨在探讨ATF3和SLC7A11在缺血性脑卒中中铁下垂的调控机制。从GEO数据库下载脑卒中相关微阵列数据集GSE58294。通过差异基因表达分析，鉴定与铁衰相关的差异表达基因（FRDEGs）。进行了生物信息学分析，包括基因本体（GO）、京都基因与基因组百科全书（KEGG）富集和蛋白质-蛋白质相互作用（PPI）网络构建。在大鼠大脑中动脉闭塞/再灌注（MCAO/R）模型和BV2小胶质细胞氧-葡萄糖剥夺/再氧合（OGD/R）模型中验证了关键枢纽基因。CCK-8法测定细胞活力。Western blot检测细胞凋亡相关蛋白，流式细胞术检测细胞凋亡。采用免疫荧光法和酶联免疫吸附法分别测定各组小鼠的活性氧（ROS）和铁离子（Fe2+）水平。生物信息学分析发现SLC7A11在中风中是一个显著改变的基因。PPI网络预测ATF3是调节SLC7A11的关键转录因子。在体外，转染si-ATF3可下调GPX4和FTH1水平，上调IREB2和ALOX15水平。此外，si-ATF3转染降低了小胶质细胞中的ROS水平和铁浓度，这一效应被铁下垂诱导剂erastin逆转。值得注意的是，在ATF3敲除后，SLC7A11的表达显著增加。我们的研究结果表明，ATF3通过结合SLC7A11启动子并抑制其表达，初步促进铁下垂，为缺血性卒中病理提供了新的机制见解。

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引用次数: 0

Multifunctionality of tissue inhibitor of metalloproteinase-1 in central nervous system diseases 金属蛋白酶-1组织抑制剂在中枢神经系统疾病中的多功能研究。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-01 DOI: 10.1016/j.brainresbull.2025.111647

Linke Zhong , Liuyang Zhao , Qiaoyan Tang , Xiaohua Zhang , Mingchao Zhou , Jiao Luo , Yulong Wang

Central nervous system (CNS) diseases are characterized by high morbidity, long disease courses, and irreversible neurological impairment, often resulting from damage to the neurovascular unit (NVU). Tissue inhibitor of metalloproteinase-1 (TIMP-1), the endogenous inhibitor of matrix metalloproteinase-9 (MMP-9), plays a pivotal role in maintaining extracellular matrix (ECM) homeostasis and regulating NVU integrity. Beyond its canonical MMP-inhibitory function, TIMP-1 exerts a wide spectrum of MMP-independent effects as a multifunctional cytokine that interacts with cell surface receptors such as CD63/β1-integrin and low-density lipoprotein receptor-related protein-1 (LRP-1). Through activation of FAK/PI3K–Akt and MAPK signaling pathways, TIMP-1 modulates astrocyte proliferation, neural stem cell adhesion and migration, endothelial barrier stability, and myelin regeneration. Altered TIMP-1 expression is closely associated with the onset, progression, and prognosis of major CNS disorders, including ischemic stroke, epilepsy, multiple sclerosis, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Accumulating evidence highlights its dual, context-dependent roles—protective in acute neuroinflammatory and ischemic injury, yet potentially profibrotic or maladaptive under chronic pathological conditions. This review comprehensively summarizes recent advances in understanding the molecular mechanisms and biological functions of TIMP-1 in CNS diseases, emphasizing its regulatory networks in neuroinflammation, neuroprotection, and neuroregeneration. A deeper understanding of TIMP-1 signaling dynamics will accelerate its translational application as a diagnostic biomarker and therapeutic target for restoring neurovascular unit function in CNS disorders.

中枢神经系统（CNS）疾病的特点是发病率高，病程长，以及不可逆的神经损伤，通常由神经血管单元（NVU）损伤引起。组织金属蛋白酶-1抑制剂（TIMP-1）是内源性基质金属蛋白酶-9 （MMP-9）抑制剂，在维持细胞外基质（ECM）稳态和调节NVU完整性中起关键作用。除了其典型的mmp抑制功能外，TIMP-1作为一种多功能细胞因子，可与细胞表面受体如CD63/β1-整合素和低密度脂蛋白受体相关蛋白-1 （LRP-1）相互作用，发挥广泛的mmp非依赖性作用。TIMP-1通过激活FAK/PI3K-Akt和MAPK信号通路，调节星形胶质细胞增殖、神经干细胞粘附和迁移、内皮屏障稳定性和髓磷脂再生。TIMP-1表达的改变与主要中枢神经系统疾病的发生、进展和预后密切相关，包括缺血性卒中、癫痫、多发性硬化症和神经退行性疾病，如阿尔茨海默病和帕金森病。越来越多的证据表明，它的双重作用，依赖于环境，在急性神经炎症和缺血性损伤中具有保护作用，但在慢性病理条件下可能会纤维化或适应不良。本文综述了TIMP-1在中枢神经系统疾病中的分子机制和生物学功能的最新研究进展，重点介绍了TIMP-1在神经炎症、神经保护和神经再生中的调控网络。对TIMP-1信号动力学的深入了解将加速其作为恢复中枢神经系统疾病中神经血管单位功能的诊断生物标志物和治疗靶点的转化应用。

{"title":"Multifunctionality of tissue inhibitor of metalloproteinase-1 in central nervous system diseases","authors":"Linke Zhong , Liuyang Zhao , Qiaoyan Tang , Xiaohua Zhang , Mingchao Zhou , Jiao Luo , Yulong Wang","doi":"10.1016/j.brainresbull.2025.111647","DOIUrl":"10.1016/j.brainresbull.2025.111647","url":null,"abstract":"<div><div>Central nervous system (CNS) diseases are characterized by high morbidity, long disease courses, and irreversible neurological impairment, often resulting from damage to the neurovascular unit (NVU). Tissue inhibitor of metalloproteinase-1 (TIMP-1), the endogenous inhibitor of matrix metalloproteinase-9 (MMP-9), plays a pivotal role in maintaining extracellular matrix (ECM) homeostasis and regulating NVU integrity. Beyond its canonical MMP-inhibitory function, TIMP-1 exerts a wide spectrum of MMP-independent effects as a multifunctional cytokine that interacts with cell surface receptors such as CD63/β1-integrin and low-density lipoprotein receptor-related protein-1 (LRP-1). Through activation of FAK/PI3K–Akt and MAPK signaling pathways, TIMP-1 modulates astrocyte proliferation, neural stem cell adhesion and migration, endothelial barrier stability, and myelin regeneration. Altered TIMP-1 expression is closely associated with the onset, progression, and prognosis of major CNS disorders, including ischemic stroke, epilepsy, multiple sclerosis, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Accumulating evidence highlights its dual, context-dependent roles—protective in acute neuroinflammatory and ischemic injury, yet potentially profibrotic or maladaptive under chronic pathological conditions. This review comprehensively summarizes recent advances in understanding the molecular mechanisms and biological functions of TIMP-1 in CNS diseases, emphasizing its regulatory networks in neuroinflammation, neuroprotection, and neuroregeneration. A deeper understanding of TIMP-1 signaling dynamics will accelerate its translational application as a diagnostic biomarker and therapeutic target for restoring neurovascular unit function in CNS disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"233 ","pages":"Article 111647"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of combined entacapone and rTMS therapy on pain severity and serum inflammatory biomarkers (IL-6 and TNF-α) in Parkinson's disease 恩他卡彭联合rTMS治疗对帕金森病疼痛严重程度和血清炎症生物标志物（IL-6和TNF-α）的影响

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-01 DOI: 10.1016/j.brainresbull.2025.111652

Yifan Yang , Jianglin Wang , Li Gao , Jiaodan Miao , Fuwei Shen , Hua Liu

Objective

To evaluate the efficacy of entacapone (EN) combined with high-frequency repetitive transcranial magnetic stimulation (rTMS) in treating pain in patients with Parkinson's disease (PD), with the primary outcome defined as the change in pain severity assessed by the Visual Analog Scale (VAS).Secondary outcomes included motor function (UPDRS), other pain dimensions (KPPS), depressive symptoms (HAMD), and levels of inflammatory markers (TNF-α and IL-6).

Methods

A total of 72 PD patients with pain were enrolled and randomly assigned to three groups: Group 1 (LD + sham stimulation), Group 2 (LD + EN + sham stimulation), and Group 3 (LD + EN + rTMS) and assessed via motor, pain, and depression scales (UPDRS/VAS/KPPS/HAMD) to evaluate the efficacy of the treatment, and also to observe the changes in the levels of interleukin (IL-6) and tumor necrosis factor (TNF-α), which are associated with pain in PD.

Results

After six months of combined pharmacotherapy and rTMS, the primary outcome, VAS score, demonstrated a significantly greater reduction in Group 3 compared to Group 2 (2.86 ± 1.25 vs. 8.22 ± 1.31, P < 0.05).In addition, from the indexes of inflammatory factors, this study found that after six months of regular and systematic treatment, the reduction in serum IL-6 and TNF-α levels was most pronounced in the combined therapy group (LD+EN+rTMS), with statistically significant differences compared to Group 2 (P = 0.003 for TNF-α).

Conclusions

High-frequency rTMS, as a non-invasive neuromodulation technique combined with EN, improves muscle rigidity, alleviates depressive symptoms, reduces pain, and attenuates inflammatory factor secretion in PD patients, can improve muscle tension, regulate depression, relieve pain, and reduce the secretion of inflammatory factors in Parkinson's patients.This combined therapy was clinically effective and demonstrated a favorable safety profile, with no serious adverse events reported and only mild, transient side effects (e.g., scalp discomfort, headache) observed in the rTMS group. However, its long-term efficacy requires further investigation.

目的：评价恩他卡酮（EN）联合高频重复经颅磁刺激（rTMS）治疗帕金森病（PD）患者疼痛的疗效，以视觉模拟量表（VAS）评估疼痛严重程度的变化为主要终点。次要结局包括运动功能（UPDRS）、其他疼痛维度（KPPS）、抑郁症状（HAMD）和炎症标志物（TNF-α和IL-6）水平。方法:总共有72 PD患者痛苦是注册和随机分为三组:第1组(LD +假刺激),组2 (LD + EN +假刺激)和组3 (LD + EN + rTMS)通过电动机和评估,痛苦,和抑郁量表(UPDRS /血管/ KPPS / HAMD)来评估治疗的疗效,并观察白介素(il - 6)水平的变化和肿瘤坏死因子(TNF -α),在PD与疼痛有关。结果：经药物联合rTMS治疗6个月后，第3组VAS评分明显低于第2组（2.86±1.25比8.22±1.31,P < 0.05）。此外，从炎症因子指标来看，本研究发现，经过6个月的常规系统治疗后，血清IL-6和TNF-α水平的降低以LD+EN+rTMS联合治疗组最为明显，与2组比较差异有统计学意义（TNF-α P = 0.003）。结论：高频rTMS作为一种无创神经调节技术，结合EN可改善PD患者肌肉强直、缓解抑郁症状、减轻疼痛、减轻炎症因子分泌，可改善帕金森患者肌肉紧张、调节抑郁、缓解疼痛、减少炎症因子分泌。这种联合治疗在临床上是有效的，并且具有良好的安全性，在rTMS组中没有严重的不良事件报告，只有轻微的、短暂的副作用（例如，头皮不适、头痛）。然而，其长期疗效有待进一步研究。

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引用次数: 0

Abnormal functional integration and effective connectivity in striatal-cortical networks with neurotransmitter system correlates in migraine without aura: A resting-state fMRI study 无先兆偏头痛的纹状体-皮层网络与神经递质系统的异常功能整合和有效连接：静息状态fMRI研究

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-01 DOI: 10.1016/j.brainresbull.2025.111653

Zhiyang Zhang , Chaorong Xie , Linglin Dong , Xu Ouyang , Xixiu Ni , Mingsheng Sun , Qixuan Fu , Qinyi Yan , Qiang Zhang , Xiao Wang , Ling Zhao

Background

Migraine without aura (MWoA) is linked to abnormal subcortical/cortical network activity and neurotransmitter dysregulation. However, the alteration of functional integration and the information flow between brain networks participated in pain sensory pathway and the patterns of neurotransmitter dysregulation during the interictal period remain unclear.

Methods

This cross-sectional study compared 53 interictal MWoA patients and 51 healthy controls using resting-state fMRI. Whole-brain functional integration (degree centrality, DC) and effective connectivity (EC) were analyzed. JuSpace toolbox mapped spatial correlation between functional alterations and neurotransmitter systems.

Results

MWoA patients showed decreased DC in the left putamen and increased DC in the left angular gyrus. Altered EC from subcortical to cortical regions included pathways from the left putamen to right medial superior frontal gyrus, supramarginal gyrus, dorsolateral superior frontal gyrus, and postcentral gyrus, as well as bilateral caudate to left angular gyrus. Cortical-to-subcortical EC changes involved right dorsolateral superior frontal gyrus to left putamen and left angular gyrus to left caudate. EC from left putamen to right postcentral gyrus inversely correlated with headache frequency, while right caudate to left angular gyrus EC positively correlated with disease duration. Altered DC patterns spatially overlapped with serotonergic, dopaminergic, and glutamate pathways and correlated with quality-of-life impairments (MSQ scores).

Conclusion

MWoA involves disrupted functional integration and bidirectional subcortical-cortical connectivity during interictal periods, associated with headache severity and neurotransmitter system imbalances. These findings highlight network-level pathophysiology and neurochemical dysregulation underlying migraine.

无先兆偏头痛（MWoA）与皮层下/皮层网络活动异常和神经递质失调有关。然而，痛觉通路参与脑网络之间的功能整合和信息流的改变，以及神经递质在间隙期的失调模式尚不清楚。方法采用静息态fMRI对53例间期MWoA患者和51例健康对照进行横断面研究。分析了全脑功能整合（度中心性，DC）和有效连通性（EC）。JuSpace工具箱绘制了功能改变与神经递质系统之间的空间相关性。结果smwoa患者表现为左壳核DC减少，左角回DC增加。皮层下至皮质区的EC改变包括左壳核至右内侧额上回、边缘上回、背外侧额上回、中央后回以及双侧尾状回至左角回的通路。皮层到皮层下的EC变化包括右背外侧额上回到左壳核和左角回到左尾状核。从左壳核到右中央后回的脑电图与头痛频率呈负相关，而从右尾状核到左角回的脑电图与病程呈正相关。改变的DC模式在空间上与血清素、多巴胺和谷氨酸通路重叠，并与生活质量受损相关（MSQ评分）。结论mwoa与头痛的严重程度和神经递质系统失衡有关，包括功能整合和皮质下-皮质双向连接的中断。这些发现强调了网络水平的病理生理和神经化学失调的潜在偏头痛。

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引用次数: 0

MultiEpilepsyNet: An EEG and MRI data based multimodal seizure detection model using hybrid deep learning model MultiEpilepsyNet：一个基于EEG和MRI数据的多模态癫痫检测模型，使用混合深度学习模型。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-01 DOI: 10.1016/j.brainresbull.2025.111645

Mohd Abdul Rahim Khan , Nasser Ali AlJarallah , Ashit Kumar Dutta , Shtwai Alsubai , Seyed Jalaleddin Mousavirad , Sunil Kumar Sharma , Ghanshyam G. Tejani , David BASSIR

Epilepsy is a critical neurological disorder that requires accurate and privacy-preserving diagnostic solutions to enable early detection and effective management. However, existing approaches face key challenges, including reliance on centralized data, poor generalizability across modalities, suboptimal feature extraction, and vulnerability to noise. To address these issues, we propose MultiEpilepsyNet, a novel multimodal seizure detection framework that integrates federated learning with hybrid deep learning models. At its core, the system introduces SeizureFed-Net, a federated architecture that enables collaborative learning from EEG and MRI data while safeguarding patient privacy. For detection, we design SeizureShieldNet, a hybrid model that fuses the temporal learning capabilities of BBIDNet (Boosted BiLSTM Intrusion Detector Network) with the adaptive decision-making of FD-TMS (Fuzzy-DQN Threat Mitigation System) under uncertainty. To further enhance model efficiency, a Jackal-Wolf Hybrid Optimizer (JWHO)—a novel combination of Golden Jackal Optimization and Grey Wolf Optimizer—is employed for optimal feature subset selection. On the imaging side, MRI preprocessing is improved through EpiSkullNet+ +, a modified 3D UNet+ + architecture tailored for precise brain segmentation. Extensive experiments on two benchmark datasets demonstrate the superiority of our approach, achieving 99.36 % accuracy on the CHB-MIT EEG dataset and 99.38 % accuracy on an epilepsy MRI dataset. Beyond accuracy, MultiEpilepsyNet demonstrates improved robustness to missing modalities, reduced training overhead via federated aggregation, and enhanced privacy preservation compared to centralized deep learning models, thereby addressing critical barriers in practical clinical deployment. These outcomes highlight the effectiveness, scalability, and real-world clinical potential of the proposed framework for epilepsy diagnosis and management.

癫痫是一种严重的神经系统疾病，需要准确和保护隐私的诊断解决方案，以便及早发现和有效管理。然而，现有的方法面临着关键的挑战，包括对集中数据的依赖，模态的泛化性差，次优特征提取以及易受噪声的影响。为了解决这些问题，我们提出了MultiEpilepsyNet，这是一个集成了联邦学习和混合深度学习模型的新型多模态癫痫检测框架。在其核心，该系统引入了一种联邦架构，可以从脑电图和MRI数据中进行协作学习，同时保护患者隐私。在检测方面，我们设计了一种将BBIDNet （boosting BiLSTM入侵检测网络）的时间学习能力与FD-TMS （Fuzzy-DQN威胁缓解系统）在不确定情况下的自适应决策能力相融合的混合模型——SeizureShieldNet。为了进一步提高模型的效率，采用了一种结合金豺狼优化算法和灰狼优化算法的豺狼混合优化算法（JWHO）进行特征子集的最优选择。在成像方面，通过episkullnet++改进了MRI预处理，episkullnet++是一种改进的3D unnet++架构，专为精确的大脑分割而设计。在两个基准数据集上的大量实验证明了我们的方法的优越性，在CHB-MIT EEG数据集上达到99.36%的准确率，在癫痫MRI数据集上达到99.38%的准确率。除了准确性之外，与集中式深度学习模型相比，MultiEpilepsyNet对缺失模式具有更好的鲁棒性，通过联合聚合减少了训练开销，并增强了隐私保护，从而解决了实际临床部署中的关键障碍。这些结果突出了提出的癫痫诊断和管理框架的有效性、可扩展性和现实世界的临床潜力。

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引用次数: 0

A comprehensive analysis of differential RNA m6A methylation modifications across the entire transcriptome in PTSD through high-throughput MeRIP sequencing 通过高通量MeRIP测序对创伤后应激障碍整个转录组中差异RNA m6A甲基化修饰的综合分析

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-01 DOI: 10.1016/j.brainresbull.2025.111665

Luodong Yang , Jiaying Lu , Keke Lu , Min Hu , Guiqing Zhang

In recent years, the increasing frequency of traumatic events has drawn greater attention to post-traumatic stress disorder (PTSD). However, its underlying biological mechanisms remain poorly understood. N6-methyladenosine (m6A) methylation is among the most common RNA modifications, yet to our knowledge, no studies to date have reported alterations in m6A methylation in PTSD. We enrolled 27 individuals with PTSD and 32 healthy controls. Quantitative real-time PCR (qRT-PCR) was used to examine expression differences of m6A methyltransferases. MeRIP-seq and RNA-seq were employed to investigate m6A methylation modifications and differentially expressed genes between PTSD patients and controls, followed by bioinformatic analysis. Our findings revealed decreased expression of METTL3 and FTO in peripheral blood mononuclear cells of PTSD patients, along with reduced global m6A methylation levels. MeRIP-seq analysis identified 1243 differentially expressed m6A peaks between groups. These peaks were annotated to 1054 differentially m6A-methylated genes, among which 183 exhibited hypermethylation and 871 showed hypomethylation in the PTSD group. RNA-seq analysis detected 662 differentially expressed genes, including 449 up-regulated and 213 down-regulated genes. In the differentially expressed lncRNA profile, 818 genes were identified, comprising 562 up-regulated and 256 down-regulated genes. GO and KEGG analyses indicated that the differentially methylated genes, mRNAs, and lncRNAs were primarily associated with inflammatory response, myelination alterations, and autonomic nervous system activation. In summary, m6A modification plays a critical role in the development and progression of PTSD. This study provides new insights into the biological mechanisms underlying the disorder.

近年来，创伤性事件的频繁发生引起了人们对创伤后应激障碍（PTSD）的关注。然而，其潜在的生物学机制仍然知之甚少。n6 -甲基腺苷（m6A）甲基化是最常见的RNA修饰之一，但据我们所知，迄今为止还没有研究报道创伤后应激障碍中m6A甲基化的改变。我们招募了27名PTSD患者和32名健康对照者。采用实时荧光定量PCR （qRT-PCR）检测m6A甲基转移酶的表达差异。采用MeRIP-Seq和RNA-seq检测PTSD患者与对照组间m6A甲基化修饰和差异表达基因，并进行生物信息学分析。我们的研究结果显示，创伤后应激障碍患者外周血单个核细胞中METTL3和FTO的表达降低，同时全球m6A甲基化水平降低。MeRIP-seq分析鉴定出1243个组间m6A表达差异峰。这些峰被注释到1054个m6a甲基化差异基因上，其中创伤后应激障碍组183个表现为高甲基化，871个表现为低甲基化。RNA-seq分析检测到662个差异表达基因，其中上调基因449个，下调基因213个。在lncRNA差异表达谱中，共鉴定出818个基因，其中上调基因562个，下调基因256个。GO和KEGG分析表明，差异甲基化的基因、mrna和lncrna主要与炎症反应、髓鞘形成改变和自主神经系统激活相关。综上所述，m6A修饰在PTSD的发生发展中起着至关重要的作用。这项研究为这种疾病的生物学机制提供了新的见解。

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引用次数: 0

Enhancing brain plasticity: Functional near-infrared spectroscopy evidence for computerized working memory training in healthy adults 增强大脑可塑性：健康成人计算机化工作记忆训练的功能近红外光谱证据。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-01 DOI: 10.1016/j.brainresbull.2025.111646

Yuntao Gao , Peng Fang , Wanying Xing , Lingwei Zeng , Hui Wang , Xia Zhu , Xiuchao Wang

Background

Understanding the neural mechanisms underlying cognitive enhancement through training is a central goal in neuroscience. Although computerized working memory training (WMT) has shown promise, its effects on brain plasticity, particularly the interplay between intrinsic network organization and task-evoked activity, remain poorly characterized. This study aimed to investigate these effects using multimodal Functional near-infrared spectroscopy (fNIRS).

Methods

We employed a randomized controlled trial with a pre-post design to investigate the effects of an 8-week adaptive computerized WMT program in healthy young adults. fNIRS was used to assess both resting-state functional connectivity (RSFC) and prefrontal cortex activation during the n-back task. Behavioral outcomes were measured across near-transfer (updating, inhibition, switching) and far-transfer (visuospatial/phonological storage) domains.

Results

Behavioral results demonstrated that, compared with the control group, the WMT group exhibited significant improvements after training not only in near-transfer tasks (e.g., updating and shifting functions) but also in far-transfer tasks (e.g., visuospatial and phonological loop tasks). Neuroimaging findings revealed multifaceted functional remodeling. During the resting state, the WMT group showed a significant increase in functional connectivity between the premotor cortex and the bilateral dorsolateral prefrontal cortex (DLPFC), along with enhanced interhemispheric frontal connectivity. When performing the n-back task, the WMT group displayed a significant reduction in activation levels (measured by total hemoglobin, HBT) in the bilateral DLPFC after training, despite improved behavioral performance, reflecting higher "neural efficiency".

Conclusions

Collectively, these findings indicate that AWMT can not only effectively enhance cognitive abilities but also induce profound functional remodeling of the prefrontal network by strengthening resting-state network integration and optimizing task-state brain resource allocation. This study provides new evidence for understanding the neural mechanisms underlying cognitive training and highlights the utility of fNIRS as a powerful tool for tracking dynamic changes in brain plasticity.

背景：通过训练了解认知增强的神经机制是神经科学的中心目标。尽管计算机化工作记忆训练（WMT）已经显示出前景，但其对大脑可塑性的影响，特别是内在网络组织和任务诱发活动之间的相互作用，仍然缺乏研究。本研究旨在利用多模态功能近红外光谱（fNIRS）研究这些影响。方法：我们采用前后设计的随机对照试验来研究8周适应性计算机化WMT程序对健康年轻人的影响。fNIRS用于评估n-back任务中静息状态功能连接（RSFC）和前额叶皮层激活。行为结果通过近迁移（更新、抑制、转换）和远迁移（视觉空间/语音存储）域进行测量。结果：行为学结果表明，与对照组相比，训练后的WMT组不仅在近迁移任务（如更新和转移功能）上表现出显著改善，而且在远迁移任务（如视觉空间和语音循环任务）上也表现出显著改善。神经影像学结果显示多方面的功能重塑。在静息状态下，WMT组运动前皮层与双侧背外侧前额叶皮层（DLPFC）之间的功能连通性显著增加，同时半球间额叶连通性增强。在执行n-back任务时，尽管行为表现有所改善，但WMT组在训练后双侧DLPFC的激活水平（通过总血红蛋白测量，HBT）显著降低，反映出更高的“神经效率”。结论：综上所述，AWMT不仅可以有效增强认知能力，还可以通过加强静息状态网络整合和优化任务状态大脑资源分配来诱导前额叶网络的深度功能重塑。这项研究为理解认知训练的神经机制提供了新的证据，并突出了fNIRS作为追踪大脑可塑性动态变化的有力工具的实用性。

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引用次数: 0

Progranulin deficiency exacerbates postoperative cognitive dysfunction via RhoA-mediated axodendritic impairment in aged mice 前颗粒蛋白缺乏通过rhoa介导的老年小鼠轴突损伤加重术后认知功能障碍。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-01 DOI: 10.1016/j.brainresbull.2025.111649

Yini Lu , Xinyu Tian , Chun Yang , Dan Wang , Ya Yan , Gang Wang , Xiaofeng Lei

Background

Postoperative cognitive dysfunction (POCD) is a debilitating complication in surgical patients, especially the elderly. yet its molecular mechanisms remain inadequately understood. This study investigates the effects of progranulin (PGRN) on hippocampal neuronal damage and cognitive impairment induced by surgical trauma.

Methods

Aged mice underwent laparotomy to model POCD, and cognitive function was assessed using the Morris Water Maze and Novel Object Recognition tests. Molecular changes were identified through RNA sequencing. Hippocampal neuronal integrity was evaluated with immunofluorescence, Golgi staining, and transmission electron microscopy. In vitro, HT22 neurons exposed to lipopolysaccharide (LPS) were treated with recombinant PGRN or RhoA-overexpressing lentivirus to investigate mechanistic pathways.

Results

Surgery significantly decreased PGRN expression in hippocampal neurons, which was associated with axonal and dendritic damage, cytoskeletal disorganization, and cognitive decline. In LPS-treated HT22 cells, loss of PGRN impaired neurite outgrowth, while exogenous PGRN restored neurite extension by inhibiting RhoA activation. Overexpression of RhoA reversed PGRN’s neuroprotective effects. In vivo, intrahippocampal PGRN administration reduced neuroinflammation, improved axodendritic function, and enhanced cognitive performance in POCD mice.

Conclusion

PGRN deficiency drives POCD pathogenesis via RhoA-mediated cytoskeletal dysfunction. Therapeutic targeting of the PGRN-RhoA axis presents a novel strategy to preserve neuronal connectivity and mitigate postoperative cognitive decline in aging populations.

背景：术后认知功能障碍（POCD）是外科患者尤其是老年人的一种衰弱性并发症。然而，其分子机制仍未被充分了解。本研究探讨颗粒前蛋白（PGRN）对外科创伤所致海马神经元损伤和认知功能障碍的影响。方法：老龄小鼠剖腹建立POCD模型，采用Morris水迷宫和新目标识别测试评估认知功能。通过RNA测序鉴定分子变化。用免疫荧光、高尔基染色和透射电镜评估海马神经元的完整性。在体外，用重组PGRN或过表达rhoa的慢病毒处理暴露于脂多糖（LPS）的HT22神经元，研究其机制途径。结果：手术显著降低了海马神经元中PGRN的表达，这与轴突和树突损伤、细胞骨架紊乱和认知能力下降有关。在lps处理的HT22细胞中，PGRN的缺失损害了神经突起的生长，而外源性PGRN通过抑制RhoA激活来恢复神经突起的延伸。RhoA的过表达逆转了PGRN的神经保护作用。在体内，海马内给予PGRN可减轻POCD小鼠的神经炎症，改善轴突功能，增强认知能力。结论：PGRN缺乏通过rhoa介导的细胞骨架功能障碍驱动POCD发病。PGRN-RhoA轴的治疗靶向提出了一种新的策略，以保持神经元连通性和减轻老年人群术后认知能力下降。

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引用次数: 0