Brain Research最新文献_第10页

Association of human plasma and cerebrospinal fluid metabolomes with vascular dementia and its subtypes: A Mendelian randomization study 人血浆和脑脊液代谢组与血管性痴呆及其亚型的关联：一项孟德尔随机研究

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-24 DOI: 10.1016/j.brainres.2025.150060

Xingkai Zhang , Yue Dong , Zhihao Zou , Ling Chen , Wen Li , Li Wang , Kai Li , Jiang He , Qinghai Shi

Background and Objective

Vascular dementia (VaD) is one of the most common subtypes of dementia after Alzheimer’s disease. Investigating body fluid metabolites is critical for understanding VaD pathophysiology and identifying potential therapeutic targets. This study employs Mendelian randomization (MR) analysis to explore the causal relationship between body fluid metabolites and VaD.

Methods

Data for VaD were retrieved from the FinnGen database. 1,400 plasma metabolites were collected from the GWAS Catalog. 338 cerebrospinal fluid (CSF) metabolites data were obtained from a subset of participants in the WADRC and WRAP studies. The inverse-variance weighted (IVW) method was used to explore causal relationships between plasma/CSF metabolites and VaD, with supplementary analyses using Weighted mode, MR-Egger, and Weighted median methods. Multiple sensitivity analyses were conducted for robustness.

Results

Following strict validation and FDR correction, significant associations (p_fdr < 0.05) were identified exclusively in plasma metabolites. The most significant metabolite was N-acetyl-aspartyl-glutamate (NAAG), with higher NAAG levels linked to reduced risks of VaD of acute onset and SVaD. Metabolonic lactone sulfate also showed significant associations across multiple disease groups, with elevated levels associated with lower disease risk, supported by FDR correction and sensitivity analyses. No significant CSF metabolites were identified after FDR correction. Disparities between CSF and plasma metabolites in disease-risk expression were observed, with only partial overlap in causal relationships (IVW, p < 0.05).

Conclusion

This study identified fluid metabolite biomarkers associated with VaD through Mendelian randomization, offering new insights and strategies for the prediction and treatment of VaD.

背景与目的血管性痴呆（VaD）是阿尔茨海默病之后最常见的痴呆亚型之一。研究体液代谢物是了解VaD病理生理和确定潜在治疗靶点的关键。本研究采用孟德尔随机化（MR）分析探讨体液代谢物与VaD之间的因果关系。方法VaD数据从FinnGen数据库中检索。从GWAS目录中收集了1400种血浆代谢物，从WADRC和WRAP研究的一部分参与者中获得了338种脑脊液代谢物数据。使用反方差加权（IVW）方法探讨血浆/脑脊液代谢物与VaD之间的因果关系，并使用加权模式、MR-Egger和加权中位数方法进行补充分析。为了稳健性，进行了多重敏感性分析。结果经过严格的验证和FDR校正，血浆代谢物中发现了显著的相关性（p_fdr < 0.05）。最显著的代谢物是n -乙酰-天冬氨酸-谷氨酸（NAAG），较高的NAAG水平与降低急性发作的VaD和SVaD的风险有关。代谢性硫酸内酯在多个疾病组中也显示出显著的相关性，FDR校正和敏感性分析支持，水平升高与疾病风险降低相关。FDR校正后未发现显著的脑脊液代谢物。脑脊液和血浆代谢物在疾病风险表达上存在差异，在因果关系上只有部分重叠（IVW, p < 0.05）。结论本研究通过孟德尔随机化方法确定了与VaD相关的体液代谢物生物标志物，为VaD的预测和治疗提供了新的见解和策略。

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引用次数: 0

Suanzaoren decoction improving chronic insomnia with little effects on functional connectivity within the sensorimotor network 酸枣仁汤改善慢性失眠症，对感觉运动网络功能连通性影响不大

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-24 DOI: 10.1016/j.brainres.2025.150037

Ping Yao , Zhiguo Guo , Yiding Han , Haohao Yan , Wuhong Lin , Ziliang Han , Min Liu , Min Chen , Jie Li , Xingyan Guo , Long-Biao Cui , Wenbin Guo , Dongsheng Lv

Purpose

This study aimed to investigate the sensorimotor network (SMN) alterations in chronic insomnia disorder (CID) following treatment with Suanzaoren decoction (SZRD) or estazolam, and to explore their associations with clinical variables and genetic variations.

Patients and methods

SMN functional connectivity (FC), effective connectivity (EC) and transcription-neuroimaging association analyses were conducted in 82 CID patients and 54 healthy controls (HCs). CID patients received either Suanzaoren decoction (SZRD), or estazolam treatment for six weeks. Subsequently, transcriptome-neuroimaging correlation analysis utilizing the Allen Human Brain Atlas was performed to identify gene profiles and neurotransmitter distributions linked to changes in FC/EC values.

Results

SZRD treatment effectively improved sleep quality. Significant differences were found in the FC and EC of SMN in patients with CID compared with HCs at baseline. The FC and EC values in the CID were associated with multiple neurotransmitter systems, including dopaminergic (DAT), cholinergic (VAChT, α4β2), and glutamatergic (NMDA) systems. Patients showed altered EC from the right fusiform gyrus to the left lateral SMN after estazolam treatment. Furthermore, we identified genes associated with FC and EC in CID, which were enriched in biological processes such as synaptic and ion transmission.

Conclusion

Our findings indicate that CID patients exhibit abnormal SMN-related intrinsic function and associated biological correlates. Aberrant SMN activity is a distinctive neuroimaging feature of CID. While estazolam affects SMN activity, SZRD has little influence on SMN-related alterations.

目的探讨慢性失眠症（CID）患者服用酸坏人汤（SZRD）或艾司唑仑（estazolam）后感觉运动网络（SMN）的改变，并探讨其与临床变量和遗传变异的关系。患者和方法对82例CID患者和54例健康对照（hc）进行了smn功能连通性（FC）、有效连通性（EC）和转录-神经影像学关联分析。CID患者接受酸枣仁汤（SZRD）或艾司唑仑治疗6周。随后，利用Allen人脑图谱进行转录组-神经成像相关分析，以确定与FC/EC值变化相关的基因谱和神经递质分布。结果sszrd治疗能有效改善睡眠质量。与基线时hcc患者相比，CID患者SMN的FC和EC有显著差异。CID的FC和EC值与多种神经递质系统有关，包括多巴胺能（DAT）、胆碱能（VAChT, α4β2）和谷氨酸能（NMDA）系统。在司他唑仑治疗后，患者表现出从右侧梭状回到左侧SMN的EC改变。此外，我们在CID中发现了与FC和EC相关的基因，这些基因在突触和离子传递等生物过程中富集。结论CID患者表现出与smn相关的内在功能异常及相关的生物学因素。异常的SMN活动是CID的一个独特的神经影像学特征。estazolam影响SMN活性，而SZRD对SMN相关改变的影响很小。

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引用次数: 0

Volume current coupling—remote direct neural coupling across the extracellular space 体积电流耦合-跨越细胞外空间的远程直接神经耦合。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-23 DOI: 10.1016/j.brainres.2025.150066

Ayumu Matani , Yusuke Takeda , Motofumi Fushimi , Akira Tsukamura

Although electrical devices should not be submerged, the brain, despite its electrical implementation, is submerged in an electrolyte solution and has indeed leakage currents as demonstrated by electroencephalograms (EEGs). Ephaptic coupling is a direct electrical neural coupling mediated by leakage currents between adjacent neurons on a microscale, and it affects spike timing. Since EEGs are detectable, meaning that tens of thousands of neurons activate synchronously, their collective leakage currents can extend the coupling over longer distances, hereafter called volume current coupling (VcC). Here, we show neural coupling (NC) = synaptic coupling (SC) + VcC and find a function of VcC. When two people, sensorily isolated but electrically connected at the heads in a skillful way to exchange their volume currents (Vcs) to avoid attenuation, were given separate left–right discrimination tasks, a significant conflict, or a task-irrelevant conditional bias, occurred in the discrimination. No SC existed between the two participants, indicating a behaviorally functional VcC. The Vc propagation path contains neurons of the person producing the Vc, and intra-person VcCs can also occur. In fact, as intra-person effects, an unconditional right-preferential bias emerged when electrically disconnected, but a task-irrelevant conditional right-preferential bias, or priming, emerged when connected. Since the skillful connection intervenes only in VcC, NC = SC + VcC is true also in individual brains and one function of VcC is to generate these biases. Since VcCs are ubiquitous in the brain as electrical crosstalk, it may be better not to study cognitive and behavioral functions in the SC alone.

虽然电气设备不应该被淹没，但大脑，尽管它的电气实现，被淹没在电解质溶液中，并且确实有泄漏电流，如脑电图（eeg）所示。Ephaptic coupling是一种在微尺度上由相邻神经元间的漏电流介导的直接电神经耦合，它会影响脉冲时间。由于脑电图是可检测的，这意味着成千上万的神经元同步激活，它们的集体泄漏电流可以将耦合扩展到更远的距离，以下称为体积电流耦合（VcC）。在这里，我们展示了神经耦合（NC） = 突触耦合（SC） + VcC，并找到了VcC的一个函数。当两个人在感觉上是隔离的，但在头部以一种巧妙的方式电连接以交换他们的体积电流（Vcs）以避免衰减时，给他们单独的左右区分任务时，在区分中发生了重大冲突或与任务无关的条件偏差。两名参与者之间不存在SC，表明存在行为功能性VcC。Vc的传播路径包含产生Vc的人的神经元，人体内的vcc也可能发生。事实上，作为人内效应，当电连接断开时，会出现无条件的右优先偏见，但当电连接时，会出现与任务无关的条件右优先偏见，或启动效应。由于熟练连接只干预VcC， NC = SC + VcC在个体大脑中也是正确的，而VcC的一个功能就是产生这些偏见。由于vcc作为电串在大脑中无处不在，因此最好不要单独研究SC的认知和行为功能。

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引用次数: 0

The role of semantic features in word production 语义特征在单词生成中的作用。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-22 DOI: 10.1016/j.brainres.2025.150065

Yufang Wang , Jurriaan Witteman , Niels O. Schiller

According to Levelt’s language production model, to name an object, speakers must first conceptualize and lexicalize the object before it can be named. Conceptualization is conducted through the semantic network, with concepts activating lexical items at the lemma level, i.e., lexicalization. So far, research has focused on the roles of semantic categories (i.e., semantic category interference) and single semantic features (i.e., semantic feature interference) but less so on the number of overlapping features. To investigate the role of the number of overlapping features in language production, we conducted a picture-word interference study in Mandarin Chinese, varying the semantic category and shape congruency whilst controlling for classifier congruency. We also recorded behavioural and electrophysiological responses. We observed a main effect of semantic category that was stronger than a main effect of shape (i.e., a semantic feature). That is, the reduction in naming accuracies, the increase in naming latencies, and the increase in ERP amplitudes between 275 – 575 ms post-stimulus onset (N400 effect) for congruent vs. incongruent conditions were larger for semantic category than for shape. In addition, we found an interaction effect between semantic category and the semantic feature ‘shape’ regarding naming accuracies and also at the electrophysiological level. We conclude that, with increasing feature overlap between word pairs, there may be more spreading of activation between such pairs in word production.

根据Levelt的语言生成模型，要命名一个对象，说话者必须首先概念化和词汇化该对象，然后才能命名。概念化是通过语义网络进行的，概念在引理层面激活词汇项目，即词汇化。到目前为止，研究主要集中在语义类别（即语义类别干扰）和单一语义特征（即语义特征干扰）的作用上，而对重叠特征数量的研究较少。为了研究语言生成过程中重叠特征的数量，我们在控制分类器一致性的同时，对汉语的语义类别和形状一致性进行了不同程度的图词干扰研究。我们还记录了行为和电生理反应。我们观察到语义范畴的主效应强于形状（即语义特征）的主效应。也就是说，在语义类别和形状条件下，一致和不一致条件下，命名准确性的降低、命名潜伏期的增加以及刺激后275 - 575 ms之间的ERP振幅的增加（N400效应）在语义类别上大于形状条件下。此外，我们发现语义类别和语义特征“形状”之间在命名准确性和电生理水平上存在交互作用。我们的结论是，随着单词对之间特征重叠的增加，在单词生成中，这些单词对之间的激活可能会有更多的传播。

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引用次数: 0

Cocaine affects astrocyte iNOS expression 可卡因影响星形胶质细胞活化和iNOS表达。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-21 DOI: 10.1016/j.brainres.2025.150068

Wei Yin, Marina Fandaros, Yanzuo Liu, Ruohan Lei, George Pittas, Serena Lee, Yingtian Pan, David A. Rubenstein, Congwu Du

Astrocytes play important roles in brain pathology. Astrocytes can express inducible nitric oxide synthase (iNOS), which is responsible for the transient production of nitric oxide (NO). Both iNOS and NO have been reported to be actively involved in cocaine addiction. We aimed to investigate if cocaine could directly affect astrocyte iNOS expression. An in vitro astrocyte culture model and an in vivo chronic cocaine mouse model were used. In the in vitro model, astrocytes from human cerebral cortex were treated with cocaine. iNOS expression was measured using solid-phase ELISA and Western blot. Changes in astrocyte morphology were quantified using a Sholl analysis. In the in vivo model, wild type C57BL/6 mice were treated with cocaine for two weeks. Mouse brain tissue, especially in the prefrontal cortex (PFC), was collected. Astrocyte number and iNOS expression were measured. The results demonstrated that cocaine could cause significant morphological changes in astrocytes in vitro. Cocaine could also cause a significant increase in astrocyte iNOS expression in vitro. The in vivo studies showed that chronic cocaine treatment significantly decreased the number of astrocytes in the mouse PFC, resulting in a decreased iNOS expression. In summary, astrocytes could directly respond to cocaine stimulation in vitro and in vivo, and iNOS was involved. Therefore, investigation into the role of astrocytes and iNOS in cocaine addiction may bring insight to new therapeutic targets for cocaine use disorder.

星形胶质细胞在脑病理中起着重要作用。星形胶质细胞可以表达诱导型一氧化氮合酶（iNOS），该酶负责一氧化氮（NO）的瞬时产生。iNOS和NO都被报道积极参与可卡因成瘾。我们的目的是研究可卡因是否能直接影响星形胶质细胞iNOS的表达。采用体外星形胶质细胞培养模型和体内慢性可卡因小鼠模型。在体外模型中，取自人类大脑皮层的星形胶质细胞被可卡因处理。采用固相ELISA和Western blot检测iNOS表达。星形胶质细胞形态的变化用肖尔分析定量。在体内模型中，野生型C57BL/6小鼠经可卡因治疗2周。收集小鼠脑组织，尤其是前额叶皮层（PFC）。检测星形胶质细胞数量及iNOS表达。结果表明，可卡因可引起体外星形胶质细胞的明显形态学改变。在体外，可卡因也能引起星形胶质细胞iNOS表达的显著增加。体内研究表明，慢性可卡因治疗可显著减少小鼠PFC中星形胶质细胞的数量，导致iNOS表达降低。综上所述，星形胶质细胞在体外和体内均可直接对可卡因刺激产生反应，iNOS参与其中。因此，研究星形胶质细胞和iNOS在可卡因成瘾中的作用可能会为可卡因使用障碍的治疗提供新的靶点。

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引用次数: 0

IGF2BP2-mediated m6A modification of IGF1R mRNA promotes neuronal senescence and cognitive decline in Alzheimer’s disease igf2bp2介导的m6A修饰IGF1R mRNA促进阿尔茨海默病的神经元衰老和认知能力下降。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-21 DOI: 10.1016/j.brainres.2025.150067

Shan Hui , Yi Long , Lemei Zhu , Wei Shi , Qing Zheng , Lihui Liang

Background

Alzheimer’s disease (AD) is characterized by cognitive decline and neuronal loss, with cellular senescence emerging as a key driver. The insulin-like growth factor-1 receptor (IGF1R) pathway is implicated in aging and AD pathology. IGF2 mRNA binding protein 2 (IGF2BP2) can stabilize IGF1R mRNA, but its role in AD-associated neuronal senescence remains unclear.

Methods

We established AD mouse models and H₂O₂-induced senescent neuronal cell models to explore the impact of IGF2BP2 in neuronal senescence and cognitive deficits. RNA pull-down assays, methylated RNA immunoprecipitation (MeRIP)-qPCR, and behavioral tests were used to elucidate the molecular mechanisms and therapeutic potential of targeting IGF2BP2.

Results

IGF2BP2 was significantly up-regulated in the hippocampal neurons of AD mice. This upregulation correlated with increased β-amyloid (Aβ) deposition, neuronal damage, and cognitive impairments. In vitro, IGF2BP2 knockdown in H₂O₂-induced senescent neurons reduced IGF1R expression and alleviated neuronal senescence, as evidenced by decreased senescence-associated secretory phenotype factors and improved cell viability. Mechanistically, IGF2BP2 stabilized IGF1R mRNA through m6A modification, enhancing its expression. Knockdown of IGF2BP2 decreased IGF1R mRNA stability and expression, thereby mitigating neuronal senescence. In AD mice, IGF2BP2 knockdown improved cognitive function, reduced Aβ deposition, and delayed neuronal senescence.

Conclusion

IGF2BP2 contributes to neuronal senescence and cognitive deficits in AD by regulating IGF1R expression through m6A modification.

背景：阿尔茨海默病（AD）的特征是认知能力下降和神经元丧失，细胞衰老是一个关键的驱动因素。胰岛素样生长因子-1受体（IGF1R）通路与衰老和AD病理有关。IGF2 mRNA结合蛋白2 （IGF2BP2）可以稳定IGF1R mRNA，但其在ad相关神经元衰老中的作用尚不清楚。方法：建立AD小鼠模型和h2o2诱导的衰老神经元细胞模型，探讨IGF2BP2在神经元衰老和认知缺陷中的作用。采用RNA拉下实验、甲基化RNA免疫沉淀(MeRIP)-qPCR和行为测试来阐明靶向IGF2BP2的分子机制和治疗潜力。结果：IGF2BP2在AD小鼠海马神经元中显著上调。这种上调与β-淀粉样蛋白（Aβ）沉积增加、神经元损伤和认知障碍相关。在体外实验中，h2o2诱导的衰老神经元中IGF2BP2的敲低可降低IGF1R的表达，减轻神经元的衰老，其表现为衰老相关分泌表型因子的减少和细胞活力的提高。机制上，IGF2BP2通过m6A修饰稳定IGF1R mRNA，增强其表达。抑制IGF2BP2可降低IGF1R mRNA的稳定性和表达，从而减轻神经元衰老。在AD小鼠中，IGF2BP2敲低可改善认知功能，减少Aβ沉积，并延缓神经元衰老。结论：IGF2BP2通过m6A修饰调节IGF1R的表达，参与AD神经元衰老和认知缺陷。

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引用次数: 0

Tongqiao huoxue decoction and its components promote angiogenesis and treat ischemic stroke via glycolysis-enhanced VEGF-A/VEGFR2 pathway 通窍活血汤及其组方通过糖酵解增强VEGF-A/VEGFR2通路促进血管生成，治疗缺血性脑卒中。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-21 DOI: 10.1016/j.brainres.2025.150069

Gongda Li , Zhongyu Liu , Wenwen Li , Rui Zhang , Hua Han , Peiliang Dong

Background

Tongqiao Huoxue Decoction (TQHXD), a representative Traditional Chinese Medicine (TCM) formula, is known for its effects in revitalizing the brain, opening the orifices, promoting blood circulation, and resolving stasis. It is widely used to treat stroke and related disorders.

Objective

This study aimed to investigate the effects of TQHXD and its component groups on post-ischemic angiogenesis in rats and to elucidate the underlying mechanisms.

Methods

Permanent middle cerebral artery occlusion (pMCAO) was performed in rats. Therapeutic effects of TQHXD were observed on days 1, 3, 5, and 7 post-surgery. Neurological deficits, infarct volume, cerebral edema, cortical cell morphology, and neuronal damage were assessed. Microvascular endothelial cells (CD31 + ) in the ischemic cortex were also evaluated. TQHXD was separated into two sub-formulas: Tongqiao Tongyang Group (TQTY) and Huoxue Huayu Group (HXHY). Drug efficacy was assessed using laser speckle contrast imaging for cerebral blood flow, and glycolysis-related markers were measured. Immunostaining was used to assess endothelial cell proliferation and vascular maturation. Protein levels were evaluated by Western blotting.

Results

TQHXD alleviated neurological deficits, reduced infarct volume, and improved the cellular morphology in the infarcted cortex of rats with MCAO rats on days 1, 3, 5, and 7. It promotes angiogenesis, manifested as a significant increase in CD31 + endothelial cells on day 7. TQHXD and its components markedly improved cerebral blood flow, increased blood perfusion velocity, and restored perfusion homogeneity in the MCAO rats. What’s more, TQHXD and HXHY enhanced glycolytic activity in endothelial cells, and promoted angiogenesis and vascular maturation. These effects were associated with the upregulation of key signaling molecules, including VEGF-A/VEGFR2, p-PI3K/PI3K, p-AKT/AKT, p-PLCγ1/PLCγ1, and p-ERK1/2/ERK1/2.

Conclusion

TQHXD and HXHY promote angiogenesis and treat ischemic stroke (IS) by activating the VEGF-A/VEGFR2-PI3K/AKT and VEGF-A/VEGFR2-PLCγ1/ERK1/2 pathways through enhanced glycolysis.

背景：通窍活血汤（TQHXD）是一种代表性的中药方剂，具有活脑、通窍、活血、化瘀的功效。它被广泛用于治疗中风和相关疾病。目的：本研究旨在探讨通络通络合剂及其各组分对大鼠缺血后血管生成的影响，并探讨其作用机制。方法：采用大鼠永久性大脑中动脉闭塞术。于术后第1、3、5、7天观察TQHXD的治疗效果。评估神经功能缺损、梗死体积、脑水肿、皮质细胞形态和神经元损伤。同时对缺血皮质微血管内皮细胞（CD31 + ）进行检测。TQHXD分为两个子配方：通桥通阳组（TQTY）和活血化瘀组（HXHY）。采用激光散斑对比成像评估脑血流的疗效，并测量糖酵解相关标志物。免疫染色用于评估内皮细胞增殖和血管成熟。Western blotting检测蛋白水平。结果：TQHXD可减轻MCAO大鼠1、3、5、7天的神经功能缺损，减少梗死体积，改善梗死皮质细胞形态。它促进血管生成，表现为在第7天CD31 + 内皮细胞显著增加。TQHXD及其组分明显改善MCAO大鼠脑血流量，增加血流灌注速度，恢复血流均匀性。TQHXD和HXHY增强内皮细胞糖酵解活性，促进血管生成和血管成熟。这些作用与关键信号分子的上调有关，包括VEGF-A/VEGFR2、p-PI3K/PI3K、p-AKT/AKT、p- plc - γ1/ plc - γ1和p-ERK1/2/ERK1/2。结论：TQHXD和HXHY通过增强糖酵解，激活VEGF-A/VEGFR2-PI3K/AKT和VEGF-A/ vegfr2 - plc - γ1/ERK1/2通路，促进血管生成，治疗缺血性卒中。

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引用次数: 0

Mitochondria serve as indispensable components of neuron-glia crosstalk in the trajectory of Alzheimer’s disease 线粒体在阿尔茨海默病的发展过程中是神经元-胶质细胞串扰的重要组成部分。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-19 DOI: 10.1016/j.brainres.2025.150040

Maryam Sardari , Oveis Hosseinzadeh Sahafi , Ameneh Rezayof

Alzheimer’s disease (AD) is a multiplex and progressive neurodegenerative disorder commonly recognized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs), and dysfunction in the cholinergic and glutamatergic systems. At the early stages of AD, mitochondrion operates as a neuroprotective organelle in both neuronal and glial cells by compensating energy fluctuations. As the disease progresses, mitochondrial function in both neurons and glial cells deteriorates, culminating in impaired cellular metabolism and glial hyperactivation. This time-dependent hyperactivation of microglia and astrocytes sequentially promotes the release of pro-inflammatory cytokines, elevates reactive oxygen species, disrupts calcium homeostasis, and increases oxidative stress. Altogether, these processes drive neuroinflammation, which both influences and is influenced by mitochondrial activity. Additionally, mitochondrial dysfunction across the disease trajectory hampers communication between neurons and glial cells, promoting excitotoxicity in neurons. This review emphasizes the vital role of mitochondrial dynamics in AD pathophysiology across different stages and explores how cell-specific targeting of mitochondrial activity could mitigate neuroinflammation, restore neuronal function, and offer potential treatment benefits. Enhancing mitochondrial function in healthy neurons and glial cells, particularly in microglia as a compensatory mechanism, especially at the early stage of the disease or restoring mitochondrial function of surviving neurons at the later stages, may promote neuroprotection and improve neuron-glia interactions, thus offering a potential strategy for AD treatment.

阿尔茨海默病（AD）是一种多发性进行性神经退行性疾病，通常以淀粉样蛋白-β (a β)斑块的积累、神经原纤维缠结（nft）以及胆碱能和谷氨酸能系统的功能障碍为特征。在阿尔茨海默病的早期阶段，线粒体通过补偿能量波动在神经元和胶质细胞中起神经保护细胞器的作用。随着疾病的进展，神经元和神经胶质细胞的线粒体功能恶化，最终导致细胞代谢受损和神经胶质过度激活。这种时间依赖性的小胶质细胞和星形胶质细胞的过度激活依次促进促炎细胞因子的释放，升高活性氧，破坏钙稳态，增加氧化应激。总之，这些过程驱动神经炎症，而神经炎症既影响线粒体活动，又受线粒体活动的影响。此外，线粒体功能障碍阻碍了神经元和神经胶质细胞之间的交流，促进了神经元的兴奋性毒性。这篇综述强调了线粒体动力学在不同阶段阿尔茨海默病病理生理中的重要作用，并探讨了细胞特异性靶向线粒体活性如何减轻神经炎症，恢复神经元功能，并提供潜在的治疗益处。增强健康神经元和神经胶质细胞（尤其是小胶质细胞）的线粒体功能，作为一种代偿机制，特别是在疾病早期或在后期恢复存活神经元的线粒体功能，可能促进神经保护并改善神经元-神经胶质相互作用，从而为阿尔茨海默病的治疗提供了一种潜在的策略。

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引用次数: 0

Trait hostility modulates the impact of cathodal tDCS on frustration-induced aggression 特质敌意调节负性tDCS对挫折攻击的影响。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-19 DOI: 10.1016/j.brainres.2025.150062

Takeshi Hirono , Hiyori Horii , Sean Draine , Ryusuke Suzuki , Rika Yano , Inaho Shishido , Yuji Inagaki , Taisuke Miyazaki , Daisuke Sawamura

Aggression, particularly reactive aggression, is a key contributor to violence and public health burdens. The left ventrolateral prefrontal cortex (VLPFC) is central to downregulating and eliciting aggression, and its influence varies with trait hostility, a dispositional tendency toward mistrust and resentment. We aimed to examine whether transcranial direct current stimulation (tDCS) of the left VLPFC alters frustration-induced aggression and whether its impact is moderated by trait hostility. Ninety-nine healthy right-handed men were randomized in a double-blind, sham-controlled trial to receive anodal, cathodal, or sham tDCS while completing an unsolvable number-sequence task. Aggression was quantified using a competitive reaction time task and physiological measurements. Although frustration induction was successful across all groups, no significant group-level differences were observed in aggression or physiological responses. However, trait hostility moderated the effect of stimulation on aggressive behavior: aggression was suppressed among individuals with low hostility but was enhanced among those with high hostility, particularly under cathodal stimulation. These findings suggest that trait hostility critically influences the behavioral impact of tDCS on aggression. Taken together, these findings underscore the dual function of the left VLPFC in anger regulation and highlight the importance of tailoring neuromodulatory interventions to individual hostility levels.

侵略，特别是反应性侵略，是造成暴力和公共卫生负担的一个主要因素。左腹外侧前额叶皮层（VLPFC）是下调和引发攻击的核心，其影响随敌意（不信任和怨恨的性格倾向）的特征而变化。我们的目的是研究经颅直流电刺激（tDCS）是否会改变左侧VLPFC的挫折性攻击，以及其影响是否会被特质性敌意所调节。在一项双盲、假对照试验中，99名健康的右撇子男性被随机分配接受阳极、阴极或假tDCS，同时完成一项无法解决的数字序列任务。通过竞争性反应时间任务和生理测量对攻击性进行量化。虽然挫折诱导在所有组中都是成功的，但在攻击或生理反应方面没有观察到显著的组水平差异。然而，特质敌意调节刺激对攻击行为的影响：低敌意个体的攻击行为被抑制，而高敌意个体的攻击行为被增强，尤其是在阴极刺激下。这些研究结果表明，敌意特质对tDCS对攻击行为的影响至关重要。综上所述，这些发现强调了左侧VLPFC在愤怒调节中的双重功能，并强调了针对个体敌意水平量身定制神经调节干预的重要性。

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引用次数: 0

Structure, Function, Pathomechanisms and Targeting of TDP-43 in Neurodegeneration TDP-43在神经退行性变中的结构、功能、病理机制及靶向作用。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-19 DOI: 10.1016/j.brainres.2025.150063

Xudong Zhang , Baiwen Zhang , Yaxin Shang , Li Zou

The TDP-43 protein has a significant relationship to the aetiology of neurodegenerative disorders. Based on its protein structure, protein modification and RNA function, this study analysed its various biological effects and the pathological effects of these biological effects in neurodegenerative diseases. It was found that TDP-43 protein undergoes conformational changes and functional alterations through protein phosphorylation, ubiquitination, SUMOylation, and acetylation, promoting its removal from the nucleus and transforming it from a normal, functional protein to an abnormally aggregated, pathological protein. It is involved in oxidative stress, inflammatory response, autophagy, angiogenesis and other biological effects. Furthermore, investigations have demonstrated that the TDP-43 protein is directly associated with neuronal growth, axon guidance, and synaptic activity, suggesting it may potentially play a significant role in the onset of degenerative neurological conditions. Based on this, the treatment strategy and future research direction are outlined to provide some insights into understanding the pathogenic mechanisms of neurodegenerative disorders and potential treatment approaches.

TDP-43蛋白与神经退行性疾病的病因学有重要关系。本研究从其蛋白结构、蛋白修饰和RNA功能等方面分析了其各种生物学效应以及这些生物学效应在神经退行性疾病中的病理作用。研究发现，TDP-43蛋白通过磷酸化、泛素化、sumo化和乙酰化发生构象改变和功能改变，促进其从细胞核中移除，使其从正常的功能蛋白转变为异常聚集的病理蛋白。它参与氧化应激、炎症反应、自噬、血管生成等生物效应。此外，研究表明，TDP-43蛋白与神经元生长、轴突引导和突触活动直接相关，这表明它可能在神经退行性疾病的发病中发挥重要作用。在此基础上，概述了神经退行性疾病的治疗策略和未来的研究方向，为了解神经退行性疾病的发病机制和潜在的治疗途径提供一些见解。

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引用次数: 0