Brain Research最新文献_第2页

Serum phosphorylated IRS-1 at Ser307 as a potential biomarker of stress-induced depressive-like behavior in rats 血清磷酸化IRS-1的Ser307作为应激诱导的大鼠抑郁样行为的潜在生物标志物。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-10 DOI: 10.1016/j.brainres.2025.150110

Sayed Soran Ghafori , Simin Mahakizadeh , Maryam Farahmandfar , Maryam Zahmatkesh , Mohammad Nasehi , Elham Bakhtiyari , Mohammad Amini , Gholamreza Hassanzadeh

Accumulating evidence suggests that inflammation mediates stress-induced depression. Elevated pro-inflammatory cytokines may affect serum phosphorylated insulin receptor substrate-1 (phospho-IRS-1) levels. This study evaluated phospho-IRS-1 at Ser³⁰⁷ as a potential biomarker associated with stress-induced depressive-like behaviors. Male Wistar rats were assigned to four groups: (1) control (unstressed, ad libitum access); (2) sham (6 h/day food and water deprivation only); (3) RS14 (6 h/day restraint stress (RS) with concurrent food/water deprivation for 14 days, then stress-free until the end of the experiment); and (4) RS28 (6 h/day RS with food/water deprivation for 28 days). On day 15, serum corticosterone, IL-1β, TNF-α, and phospho-IRS-1 at Ser³⁰⁷ were measured, and depressive-like behaviors were assessed using FST and TST. Hippocampal histology was performed on days 15 and 30 using Nissl staining. On day 30, serum IL-1β, TNF-α, and phospho-IRS-1 at Ser³⁰⁷ were quantified, and behavioral assessments were conducted using FST and TST. On day 15, corticosterone, IL-1β, and TNF-α were significantly elevated in RS14 and RS28 vs. control/sham (P < 0.05), while phospho-IRS-1 at Ser³⁰⁷ and FST/TST outcomes showed no differences. On both days 15 and 30, the percentage of pyknotic neurons in RS14 and RS28 was higher than in control/sham, and on day 30, RS28 showed a further significant increase compared with RS14. On day 30, RS14 exhibited elevated IL-1β and TNF-α vs. control/sham, but phospho-IRS-1 at Ser³⁰⁷ and depressive-like behaviors were not significantly changed. In contrast, RS28 showed further increases in IL-1β, TNF-α, and phospho-IRS-1 at Ser³⁰⁷, along with altered FST (swimming, climbing, immobility times) and TST (immobility latency/time) parameters compared with all other groups (P < 0.05). These findings suggest that increased serum phospho-IRS-1 at Ser³⁰⁷ may serve as a biomarker for stress-induced depressive-like behaviors.

越来越多的证据表明，炎症介导应激性抑郁。升高的促炎细胞因子可能影响血清磷酸化胰岛素受体底物-1（磷酸化irs -1）水平。本研究评估了磷酸化irs -1的Ser307位点作为与应激诱导的抑郁样行为相关的潜在生物标志物。雄性Wistar大鼠分为四组：(1)对照组（无应激，自由进入）；(2)假手术（6 小时/天，仅限食物和水）；(3) RS14（6 h/d限制性应激，同时剥夺食物/水，持续14 d，然后无应激至试验结束）；(4) RS28（6 h/d RS，剥夺食物/水28 d）。第15天，测定血清皮质酮、IL-1β、TNF-α和磷酸化irs -1 Ser307位点，并采用FST和TST评估抑郁样行为。第15、30天采用尼氏染色进行海马组织学观察。第30天，定量血清IL-1β、TNF-α和磷酸化irs -1 Ser307位点，并采用FST和TST进行行为评估。第15天，与对照组/假手术相比，RS14和RS28的皮质酮、IL-1β和TNF-α显著升高（P < 0.05），而Ser307和FST/TST的磷酸化irs -1结果无差异。在第15天和第30天，RS14和RS28的收缩神经元百分比均高于对照组/假手术组，在第30天，RS28与RS14相比进一步显著增加。第30天，与对照组/假手术组相比，RS14表现出IL-1β和TNF-α升高，但磷酸化irs -1 Ser307位点和抑郁样行为没有显著改变。与其他各组相比，RS28组IL-1β、TNF-α和磷酸化irs -1 Ser307位点进一步升高，FST（游泳、攀爬、静止时间）和TST（静止潜伏期/时间）参数改变（P < 0.05）。这些发现表明，血清中Ser307位点磷酸化irs -1的升高可能是应激诱导的抑郁样行为的生物标志物。

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引用次数: 0

Astrocyte regulates neuroinflammation and myelination in BCCAO-related cognitive impairment via the PIAS1-STAT1 pathway 星形胶质细胞通过PIAS1-STAT1通路调节bccao相关认知障碍的神经炎症和髓鞘形成。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-09 DOI: 10.1016/j.brainres.2025.150107

Hao Ding , Shuo Wu , Dongya Huang , Lianbiao Shan

Vascular dementia (VaD) ranks as the second most common form of cognitive impairment worldwide, surpassed only by Alzheimer’s disease (AD), yet its pathophysiological mechanisms are still not fully understood. This study sought to explore the mechanisms underlying secondary cognitive decline after transient cerebral ischemia, employing a temporary bilateral common carotid artery occlusion (BCCAO) model to mimic clinical cerebral ischemia–reperfusion (I/R) conditions. Dynamic detection of model mice revealed no significant loss of hippocampal neurons after surgery. Nevertheless, at 12 weeks post-surgery, the mice exhibited obvious myelin loss accompanied by cognitive decline. Further intervention studies showed that the microglial depleter PLX5622 failed to effectively rescue myelin damage and cognitive impairment, while astrocytes remained persistently activated.

Analysis of the differential expression profile of astrocytes from a VaD patient brain tissue database identified Protein Inhibitor of Activated STAT1 (PIAS1) as a key regulator, which was significantly downregulated in the astrocytes of VaD patients—this finding was validated in model mice. Behavioral assessments revealed that targeted overexpression of PIAS1 in astrocytes, achieved through adeno-associated viral (AAV) delivery, markedly ameliorated cognitive deficits, attenuated myelin injury, and suppressed astrocytic inflammatory responses. In parallel, in vitro studies using primary astrocyte cultures demonstrated that PIAS1 exerts its anti-inflammatory effects by modulating the signal transducer and activator of transcription 1 (STAT1) signaling pathway.

In summary, the findings of this study demonstrate that reduced expression of PIAS1 in astrocytes following mild cerebral ischemia plays a crucial role in triggering secondary cognitive deficits and myelin degeneration. Furthermore, PIAS1 regulates astrocyte-mediated inflammatory responses via a STAT1-dependent pathway, offering new perspectives on the underlying mechanisms of VaD and potential therapeutic interventions.

血管性痴呆（VaD）是全球第二大最常见的认知障碍形式，仅次于阿尔茨海默病（AD），但其病理生理机制仍未完全了解。本研究旨在探讨短暂性脑缺血后继发性认知能力下降的机制，采用暂时性双侧颈总动脉闭塞（BCCAO）模型模拟临床脑缺血再灌注（I/R）情况。模型小鼠的动态检测显示，术后海马神经元未见明显损失。然而，在手术后12 周，小鼠表现出明显的髓磷脂丢失，并伴有认知能力下降。进一步的干预研究表明，小胶质细胞消耗剂PLX5622不能有效地挽救髓磷脂损伤和认知障碍，而星形胶质细胞仍然持续激活。通过对VaD患者脑组织数据库中星形胶质细胞差异表达谱的分析，发现VaD患者星形胶质细胞中PIAS1 （Protein Inhibitor of Activated STAT1）是一个关键的调控因子，其在VaD患者的星形胶质细胞中显著下调，这一发现在模型小鼠中得到了验证。行为评估显示，通过腺相关病毒（AAV）递送，PIAS1在星形胶质细胞中靶向过表达，显著改善认知缺陷，减轻髓鞘损伤，抑制星形胶质细胞炎症反应。与此同时，利用原代星形胶质细胞培养的体外研究表明，PIAS1通过调节信号转导和转录激活因子1 （STAT1）信号通路发挥其抗炎作用。综上所述，本研究结果表明，轻度脑缺血后星形胶质细胞中PIAS1的表达降低在引发继发性认知缺陷和髓鞘变性中起着至关重要的作用。此外，PIAS1通过stat1依赖途径调节星形胶质细胞介导的炎症反应，为VaD的潜在机制和潜在的治疗干预提供了新的视角。

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引用次数: 0

Unforgettable food memories in overweight/obese individuals-Evidence from Think/No-Think experiment 超重/肥胖个体难以忘怀的食物记忆——来自思考/不思考实验的证据。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-09 DOI: 10.1016/j.brainres.2025.150108

Zhuoyu Zheng , Chenrui Luo , Peisen Yuan , Ke Cui , Li Luo , Yong Liu , Jia Zhao

Appetite regulation is critically influenced by food-related memories, and the ability to inhibit retrieval of such mnemonic content may serve to attenuate cravings. While inhibitory control is often conceptualized in terms of motor response suppression, the specific mechanisms underlying the suppression of food-related memories remain poorly characterized in overweight and obese (OO) individuals. This study investigated the behavioral and neurophysiological correlates of direct memory suppression in this population. Forty-five young adults performed a Think/No-Think (TNT) task using highand low-calorie food images during electroencephalographic (EEG) recording. We analyzed event-related potentials (ERPs) and time-frequency representations (TFRs). Behaviorally, the OO group demonstrated enhanced memory accuracy for food cues compared to normal-weight (NW) controls, specifically during Think trials. Neurophysiological data revealed a significant modulation of the N200 component by calorie content (p = 0.008). the late positive potential (LPP) was sensitive to both instruction (Think/No-Think; p = 0.04) and group membership (p= 0.029). Timefrequency analysis demonstrated that beta-band oscillatory power differentiated between Think and No-Think conditions (p = 0.001) and revealed a significant group-bycalorie interaction (p = 0.007). Collectively, these findings indicate that OO individuals exhibit altered neural dynamics and heightened engagement of neurocognitive resources during the suppression of food-related memories. This work elucidates a potential mnemonic mechanism contributing to maladaptive eating behaviors and posits that interventions targeting memory inhibition could offer a novel pathway for mitigating obesity-related cognitive dysregulation.

食欲调节受到与食物有关的记忆的严重影响，抑制这种记忆内容的检索的能力可能有助于减少渴望。虽然抑制性控制通常被概念化为运动反应抑制，但在超重和肥胖（OO）个体中，抑制食物相关记忆的具体机制仍然缺乏特征。本研究调查了该人群中直接记忆抑制的行为和神经生理相关因素。45名年轻人在脑电图（EEG）记录过程中使用高热量和低热量食物图像进行思考/不思考（TNT）任务。我们分析了事件相关电位（ERPs）和时频表征（TFRs）。在行为上，与正常体重的对照组相比，OO组对食物线索的记忆准确性有所提高，特别是在思考试验中。神经生理学数据显示，卡路里含量显著调节N200成分（p = 0.008）。后期正电位（LPP）对指导（思考/不思考；p= 0.04）和群体成员（p= 0.029）均敏感。时间频率分析表明，思考和不思考条件下的β波段振荡功率存在差异（p = 0.001），并显示了显著的组-卡路里相互作用（p = 0.007）。总的来说，这些发现表明，在食物相关记忆的抑制过程中，OO个体表现出改变的神经动力学和神经认知资源的高度参与。这项研究阐明了一种潜在的助记机制，有助于适应不良的饮食行为，并假设以记忆抑制为干预目标，可能为减轻肥胖相关的认知失调提供一种新的途径。

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引用次数: 0

Activation of PPARα by gemfibrozil lowers tau-associated neuropathology in the MAPT mouse model of Alzheimer's disease. 吉非罗齐激活PPARα降低阿尔茨海默病MAPT小鼠模型中tau相关的神经病理学

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-07 DOI: 10.1016/j.brainres.2025.150089

Moumita Majumder, Debashis Dutta, Ramesh K Paidi, Kalipada Pahan

The current dogma states that inhibiting tau accumulation and its associated neuropathologies might be a relevant strategy to prevent neuronal loss and cognitive dysfunction in Alzheimer's disease (AD). The present study demonstrates the therapeutic potential of an FDA-approved lipid lowering drug and an agonist of peroxisome proliferator and activated receptor α (PPARα), called gemfibrozil, in reducing tau accumulation and associated neuropathologies in the MAPT (PS19) mouse model of AD, expressing P301S mutated form of human tau protein in neurons. Daily oral treatment of gemfibrozil in MAPT mice reduced total tau and phosphorylated form of tau in the hippocampal subregions including CA1 and DG. Concurrently, gemfibrozil treatment upregulated PPARα level in the hippocampus and that was accompanied with inhibition of microgliosis and astrogliosis. Gemfibrozil also attenuated the loss of synaptic plasticity as determined by the expression of post-synaptic protein, PSD95, and calcium influx in the hippocampal tissue. The instrumental role of PPARα in gemfibrozil-mediated reduction of tauopathy was confirmed as PPARα deficiency in MAPT mice significantly augmented tau and phospho-tau accumulation in the hippocampus and gemfibrozil treatment failed to reverse tau pathology and gliosis in the brain of PPARα deficient MAPT mice. Lastly, gemfibrozil improved the cognitive function of MAPT mice during the symptomatic phase of disease progression, but it failed to reverse cognitive impairment in the PPARα deficient MAPT mice. These data suggest that neuroprotective effects of gemfibrozil in MAPT mice is mediated by PPARα. Moreover, targeting PPARα by small molecules like gemfibrozil may hold translational potential against tauopathy.

目前的观点认为，抑制tau积聚及其相关的神经病理可能是预防阿尔茨海默病（AD）中神经元丢失和认知功能障碍的相关策略。本研究证明了fda批准的降脂药物和过氧化物酶体增殖物和活化受体α (PPARα)激动剂，称为gemfibrozil，在MAPT (PS19) AD小鼠模型中减少tau积聚和相关神经病理的治疗潜力，在神经元中表达P301S突变形式的人tau蛋白。在MAPT小鼠中每日口服吉非罗齐可减少海马亚区（包括CA1和DG）中总tau和磷酸化形式的tau。同时，吉非西可上调海马PPARα水平，并伴有小胶质细胞增生和星形胶质细胞增生的抑制。通过突触后蛋白PSD95的表达和海马组织钙内流来确定，Gemfibrozil还能减轻突触可塑性的丧失。在MAPT小鼠中，PPARα缺乏显著增加海马中tau和磷酸化tau的积累，而gemfibrozil治疗未能逆转PPARα缺乏的MAPT小鼠的tau病理和脑胶质瘤，证实了PPARα在gemfibrozil介导的tau病减少中的重要作用。最后，吉非罗齐在疾病进展的症状期改善了MAPT小鼠的认知功能，但未能逆转PPARα缺陷MAPT小鼠的认知功能障碍。这些数据表明，吉非罗齐对MAPT小鼠的神经保护作用是由PPARα介导的。此外，小分子如吉非齐尔靶向PPARα可能具有抗牛头病的翻译潜力。

{"title":"Activation of PPARα by gemfibrozil lowers tau-associated neuropathology in the MAPT mouse model of Alzheimer's disease.","authors":"Moumita Majumder, Debashis Dutta, Ramesh K Paidi, Kalipada Pahan","doi":"10.1016/j.brainres.2025.150089","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.150089","url":null,"abstract":"<p><p>The current dogma states that inhibiting tau accumulation and its associated neuropathologies might be a relevant strategy to prevent neuronal loss and cognitive dysfunction in Alzheimer's disease (AD). The present study demonstrates the therapeutic potential of an FDA-approved lipid lowering drug and an agonist of peroxisome proliferator and activated receptor α (PPARα), called gemfibrozil, in reducing tau accumulation and associated neuropathologies in the MAPT (PS19) mouse model of AD, expressing P301S mutated form of human tau protein in neurons. Daily oral treatment of gemfibrozil in MAPT mice reduced total tau and phosphorylated form of tau in the hippocampal subregions including CA1 and DG. Concurrently, gemfibrozil treatment upregulated PPARα level in the hippocampus and that was accompanied with inhibition of microgliosis and astrogliosis. Gemfibrozil also attenuated the loss of synaptic plasticity as determined by the expression of post-synaptic protein, PSD95, and calcium influx in the hippocampal tissue. The instrumental role of PPARα in gemfibrozil-mediated reduction of tauopathy was confirmed as PPARα deficiency in MAPT mice significantly augmented tau and phospho-tau accumulation in the hippocampus and gemfibrozil treatment failed to reverse tau pathology and gliosis in the brain of PPARα deficient MAPT mice. Lastly, gemfibrozil improved the cognitive function of MAPT mice during the symptomatic phase of disease progression, but it failed to reverse cognitive impairment in the PPARα deficient MAPT mice. These data suggest that neuroprotective effects of gemfibrozil in MAPT mice is mediated by PPARα. Moreover, targeting PPARα by small molecules like gemfibrozil may hold translational potential against tauopathy.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"150089"},"PeriodicalIF":2.6,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

ZFP36 attenuates neuronal apoptosis and pyroptosis through inhibiting TXNIP/NLRP3 pathway in hypoxic-ischemic brain damage ZFP36通过抑制TXNIP/NLRP3通路在缺氧缺血性脑损伤中减轻神经元凋亡和焦亡。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-06 DOI: 10.1016/j.brainres.2025.150088

Hengjiang Guo, Yan Jiang, Zhiqing Gu, Hongyun Li, Shumeng Wang, Mingwei Zhao, Jingwen Mao, Rong Wei, Change Zhu

Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal mortality and long-term neurological impairment. Neuroinflammation plays a critical role in neuronal injury following HIBD. Zinc finger protein 36 (ZFP36), an RNA-binding protein that targets adenine-uridine-rich elements (AREs), exhibits anti-inflammatory properties, yet its role in HIBD remains unclear. In this study, we observed significant upregulation of ZFP36 expression in the hippocampal neurons of neonatal rats with HIBD and in HT22 hippocampal neuronal cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Knockdown of ZFP36 via adeno-associated virus (AAV) in neonatal rats exacerbated HIBD-induced hippocampal neuronal injury, cerebral infarction, and neurological deficits, whereas ZFP36 overexpression via AAV markedly ameliorated these outcomes. Similarly, ZFP36 knockdown in HT22 cells using lentivirus aggravated OGD/R-induced neuronal apoptosis and pyroptosis, while ZFP36 overexpression conferred protection. Mechanistically, ZFP36 can directly binds to the ARE within the 3′-untranslated region (3′-UTR) of thioredoxin-interacting protein (TXNIP), a key activator of the NOD-like receptor protein 3 (NLRP3) inflammasome, promoting TXNIP mRNA destabilization and degradation. This reduction in TXNIP impairs the TXNIP-NLRP3 interaction, thereby inhibiting NLRP3 inflammasome activation and neuroinflammation in HIBD. Collectively, our findings suggest that ZFP36 protects against HIBD through suppressing the TXNIP/NLRP3 inflammasome pathway and highlight ZFP36 as a potential therapeutic target for HIBD.

缺氧缺血性脑损伤（HIBD）是新生儿死亡和长期神经损伤的主要原因。神经炎症在HIBD后的神经元损伤中起关键作用。锌指蛋白36 （ZFP36）是一种靶向腺嘌呤-尿嘧啶富元素（AREs）的rna结合蛋白，具有抗炎特性，但其在HIBD中的作用尚不清楚。在本研究中，我们观察到新生大鼠HIBD海马神经元和氧糖剥夺/再氧化（OGD/R） HT22海马神经元细胞中ZFP36的表达显著上调。在新生大鼠中，通过腺相关病毒（AAV）敲低ZFP36加重了hibd诱导的海马神经元损伤、脑梗死和神经功能缺损，而通过AAV过表达ZFP36可显著改善这些结果。同样，在HT22细胞中使用慢病毒敲低ZFP36会加重OGD/ r诱导的神经元凋亡和焦亡，而过表达ZFP36则具有保护作用。在机制上，ZFP36可以直接结合硫氧还蛋白相互作用蛋白（TXNIP）的3'-非翻译区（3'-UTR）内的ARE， TXNIP是nod样受体蛋白3 （NLRP3）炎症小体的关键激活剂，促进TXNIP mRNA的不稳定和降解。TXNIP的减少损害了TXNIP-NLRP3的相互作用，从而抑制了NLRP3炎症小体的激活和HIBD的神经炎症。总之，我们的研究结果表明ZFP36通过抑制TXNIP/NLRP3炎性体途径来预防HIBD，并强调ZFP36是HIBD的潜在治疗靶点。

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引用次数: 0

APOE4 exacerbates post-stroke cognitive impairments and Aβ deposition in a photothrombotic mouse model 在光血栓小鼠模型中，APOE4加重脑卒中后认知障碍和a β沉积。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-06 DOI: 10.1016/j.brainres.2025.150105

Xiang-yu Liu , Jia-xing Yuan , Cheng Wu , Qi Liu , Qian Ding , Cai-ling Zhang , Yue Lan , Guang-qing Xu

Background

Apolipoprotein E4 (APOE4) is considered a potential risk factor for post-stroke cognitive impairment (PSCI); however, clinical evidence remains conflicting and the mechanisms are poorly understood. Amyloid-β (Aβ) progressively accumulates post-stroke and may drive PSCI pathogenesis.

Objectives

This study aims to investigate whether APOE4 worsens cognitive outcomes after ischemic stroke, with particular emphasis on its impact on Aβ pathology.

Methods

We established a reproducible ischemic stroke model using the photothrombotic occlusion method in humanized APOE3- and APOE4-targeted replacement mice. Cognitive function was evaluated 28 days post-stroke by novel object recognition and Morris water maze tests. Subsequently, infarct volume was quantified using Nissl staining, while immunofluorescence analyses were performed to assess neuronal loss, microglial activation and Aβ deposition in the peri-infarct region and ipsilateral hippocampus.

Results

Compared to APOE3 stroke mice, APOE4 stroke mice exhibited exacerbated cognitive deficits, alongside larger infarcts, greater neuronal loss, and heightened neuroinflammation. Critically, APOE4 stroke mice also showed significantly increased Aβ deposition. Correlation analyses revealed that the extent of Aβ accumulation in the hippocampal CA1 region was negatively correlated with cognitive performance. Additionally, Aβ deposition was positively correlated with microglial activation and neuronal loss.

Conclusions

These findings suggest that APOE4 serves as an adverse risk factor for PSCI, potentially facilitating its progression through the elevation of Aβ accumulation, thereby providing a novel target for precise intervention.

载脂蛋白E4 （APOE4）被认为是脑卒中后认知功能障碍（PSCI）的潜在危险因素；然而，临床证据仍然相互矛盾，其机制也知之甚少。淀粉样蛋白-β (Aβ)在脑卒中后逐渐积累，并可能驱动PSCI发病机制。目的：本研究旨在探讨APOE4是否会恶化缺血性脑卒中后的认知结果，特别强调其对Aβ病理的影响。方法：采用光血栓闭塞法在人源化APOE3-和apoe4靶向替代小鼠中建立可重复的缺血性卒中模型。脑卒中后28 天通过新物体识别和Morris水迷宫测试评估认知功能。随后，使用尼氏染色定量梗死体积，同时进行免疫荧光分析以评估梗死周围区和同侧海马的神经元损失、小胶质细胞激活和Aβ沉积。结果：与APOE3中风小鼠相比，APOE4中风小鼠表现出更严重的认知缺陷、更大的梗死、更大的神经元损失和更高的神经炎症。关键的是，APOE4中风小鼠也显示出显著增加的Aβ沉积。相关分析显示，海马CA1区Aβ积累程度与认知能力呈负相关。此外，Aβ沉积与小胶质细胞活化和神经元损失呈正相关。结论：这些发现表明APOE4作为PSCI的不利风险因素，可能通过升高a β积累促进其进展，从而为精确干预提供了新的靶点。

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引用次数: 0

Effects of anodal transcranial direct current stimulation over the right posterior parietal cortex on Simon task and flanker task performance 经颅直流电刺激右后顶叶皮层对Simon任务和flanker任务表现的影响。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-05 DOI: 10.1016/j.brainres.2025.150100

Sho Kojima , Kako Tanabe , Mitsuki Todoroki , Hideaki Onishi

Introduction

Stimulus-response compatibility (SRC) tasks test cognitive judgment by requiring discrimination between relevant and irrelevant information. This study explored the effects of anodal transcranial direct current stimulation (tDCS) over the posterior parietal cortex (PPC) on performance in the Simon and Flanker tasks.

Methods

Fifteen healthy, right-handed adults (age: 21.3 ± 0.6 years) participated in the study, completing the Simon and Flanker tasks before and after active and sham tDCS conditions in a crossover design. Sessions were randomized with a 5-day interval between them. Anodal tDCS (1 mA) was applied to the right PPC for 15 min, with sham stimulation lasting 30 s. Task performance was evaluated based on reaction time and accuracy pre- and post-stimulation. Statistical analyses were conducted using nonparametric tests.

Results

For congruent Simon task trials, reaction times significantly decreased post-intervention for active and sham tDCS, with no change for incongruent trials. The SRC effect significantly decreased following active tDCS but remained unchanged with sham stimulation. For the Flanker task, no significant differences in SRC effects were observed pre- and post-intervention.

Conclusions

Anodal tDCS over the right PPC improved Simon task performance by reducing the SRC effect. No significant changes were observed in the Flanker task, suggesting that the PPC’s role in interference control may be specific to spatial compatibility effects, as seen in the Simon task.

刺激-反应相容性（SRC）任务通过对相关和不相关信息的区分来测试认知判断。本研究探讨了经颅直流电刺激（tDCS）对后顶叶皮层（PPC）在Simon和Flanker任务中的作用。方法：15名健康的右撇子成人（年龄：21.3 ± 0.6 岁）参与研究，采用交叉设计，在活动和假tDCS条件前后分别完成Simon和Flanker任务。疗程随机化，间隔5天。负极tDCS（1 mA）作用于右侧PPC 15 min，假性刺激持续30 s。任务表现是根据刺激前和刺激后的反应时间和准确性来评估的。采用非参数检验进行统计分析。结果：对于一致Simon任务试验，主动和假tDCS干预后的反应时间显著减少，而不一致试验的反应时间没有变化。活跃tDCS后SRC效应显著降低，但假性刺激后仍保持不变。在侧卫任务中，干预前和干预后的SRC效果没有显著差异。结论：右PPC上的阳极tDCS通过减少SRC效应改善Simon任务表现。在Flanker任务中没有观察到明显的变化，这表明PPC在干扰控制中的作用可能是特定于空间相容性效应的，正如在Simon任务中所看到的那样。

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引用次数: 0

Hyperandrogenism associated deregulation of hippocampal adipokines may contribute to impaired memory function in mice 高雄激素症相关的海马脂肪因子失调可能导致小鼠记忆功能受损。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-05 DOI: 10.1016/j.brainres.2025.150101

Ayushmita Dutta , Rahul Kumar , Guruswami Gurusubramanian , Vikas Kumar Roy

The elevation of androgen is called as hyperandrogenemia. Despite endocrinological imbalances, hyperandrogenism has also been linked to slight impairment in the cognitive functions along with depression and anxiety. Since the hippocampus regulates these function and also expresses adipokines such as leptin and adiponectin, and these adipokines have also shown deregulation in the hyperandrogenised conditions. Thus, this study aimed to explore the expression of leptin, leptin receptor, adiponectin, adipoR1 and adipoR2 along with androgen receptor and estrogen receptors in the hippocampus of letrozole-induced hyperandrogenised mice. Our results showed hyperandrogenism up-regulated the expression of leptin receptor and adipoR1, while down-regulated the expression of adipoR2. The immunostaining of leptin showed increased abundance and decreased abundance of adiponectin in the hippocampus. Furthermore, expression of androgen receptor was up-regulated and estrogen receptors expressions were down-regulated in the hippocampus of hyperandrogenised mice. The marker of apoptotic protein, active caspase3 was elevated and anti-apoptotic protein; BCL2 was suppressed in the letrozole-treated mice. Thus, it can be suggested that hyperandrogenism may be associated with deregulation of adipokines and steroid signaling along with neuronal degeneration in the hippocampus, and might also be linked to behavioral issues in the hyperandrogenised conditions with declined in spatial working memory when assessed in Y-Maze test. Since, our study was aimed to explore the expression of above proteins and linking with cognitive impairment in the hyperandrogenised conditions, yet, it is speculative and requires further investigation with auxiliary behavioral tests.

升高的雄激素被称为高雄激素血症。除了内分泌失衡，高雄激素症还与认知功能的轻微损害以及抑郁和焦虑有关。由于海马体调节这些功能，同时也表达脂肪因子，如瘦素和脂联素，而这些脂肪因子在高雄激素化条件下也显示出解除管制。因此，本研究旨在探讨来曲唑诱导的高雄激素化小鼠海马中瘦素、瘦素受体、脂联素、adipoR1和adipoR2以及雄激素受体和雌激素受体的表达。结果显示，高雄激素血症上调瘦素受体和adipoR1的表达，下调adipoR2的表达。瘦素免疫染色显示海马区脂联素丰度升高，脂联素丰度降低。高雄激素化小鼠海马雄激素受体表达上调，雌激素受体表达下调。凋亡蛋白标志物活性caspase3升高，抗凋亡蛋白升高；来曲唑处理小鼠BCL2被抑制。因此，我们可以认为，雄激素过多可能与脂肪因子和类固醇信号的失调以及海马体中的神经元变性有关，也可能与y迷宫测试中评估的空间工作记忆下降的雄激素过多条件下的行为问题有关。因此，我们的研究旨在探索上述蛋白的表达及其与高雄激素化条件下认知障碍的联系，然而，这是推测性的，需要进一步的辅助行为测试来研究。

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引用次数: 0

Evolution of users’ subjective experience over three training sessions with an EEG Motor-Imagery Brain–Computer Interface (MI-BCI) 基于脑电运动-图像脑机接口（MI-BCI）的三次训练中用户主观体验的演变。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-04 DOI: 10.1016/j.brainres.2025.150085

Aline Roc , Léna Kolodzienski , Pauline Dreyer , Aurélien Appriou , Thibaut Monseigne , Fabien Lotte

Motor Imagery-based Brain–Computer Interfaces (MI-BCIs) have been shown to be promising for numerous applications, including sport training and entertainment for healthy users, but also for improving or restoring functions in neurological and neuropsychiatric disorders, e.g., for motor rehabilitation post-stroke or for attention training in attention deficits. Reliable interactions with such MI-BCIs require a heavy training process for both the machine and the user. Yet, how User eXperience (UX) evolves during standard training is still largely unclear, both within and between sessions/days. Through an exploratory study, we investigated the variations of users’ answers to a UX questionnaire when training with a standard left vs. right-hand MI-BCI. 24 healthy novice users engaged in 3 training sessions (with 12 runs each) on different days. Each short run was followed by six questions on screen measuring UX factors on scales from 1 to 10: mental demand, performance, mental effort, frustration, mental fatigue and anxiety. Interestingly, BCI performances did not correlate with any subjective UX measure in this study. However, a time effect was observed. Within session, the results suggested that mental demand, effort, and fatigue significantly augmented during BCI operation, and that frustration significantly fluctuated but did not differ pre- vs. post-session. Between sessions, the first session was rated significantly more challenging than the other two regarding frustration, anxiety, mental demand, mental effort and mental fatigue. This highlights the importance of conducting studies across sessions and of considering the users’ mental states during BCI use, for improving UX and thus possibly BCI treatment outcome.

基于运动图像的脑机接口（mi - bci）已被证明有许多应用前景，包括健康用户的运动训练和娱乐，但也用于改善或恢复神经和神经精神疾病的功能，例如中风后的运动康复或注意力缺陷的注意力训练。与这种mi - bci进行可靠的交互需要对机器和用户进行大量的训练。然而，用户体验（UX）在标准培训期间是如何发展的，无论是在课程内还是在课程之间。通过一项探索性研究，我们调查了在使用标准的左MI-BCI和右手MI-BCI进行训练时，用户对UX问卷的回答的变化。24名健康的新手在不同的日子进行3次训练（每次12次）。每次短期测试之后，屏幕上都有6个问题，以1到10的等级衡量用户体验因素：心理需求、表现、心理努力、挫败感、心理疲劳和焦虑。有趣的是，在这项研究中，BCI的表现与任何主观的用户体验测量都没有关联。然而，观察到时间效应。在治疗期间，结果表明脑机接口手术期间精神需求、努力和疲劳显著增加，挫折感显著波动，但与治疗前和治疗后没有差异。在两组测试之间，第一组测试在挫折、焦虑、心理需求、心理努力和心理疲劳方面被评为比其他两组更具挑战性。这突出了跨会话进行研究和考虑用户在BCI使用期间的精神状态的重要性，以改善用户体验，从而可能改善BCI治疗结果。

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引用次数: 0

ZNF655-mediated neuroprotection in cerebral ischemia-reperfusion injury via Akt/Nrf2 pathway modulation znf655介导的Akt/Nrf2通路在脑缺血再灌注损伤中的神经保护作用。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-04 DOI: 10.1016/j.brainres.2025.150091

Wanyi Wei , Zongkai Wu , Yuehong Yue , Yang Zhang , Hebo Wang

Background

Cerebral ischemia–reperfusion injury (CIRI) involves complex pathological processes, including oxidative stress, inflammatory responses, and apoptosis. Zinc finger protein 655 (ZNF655) is implicated in the regulation of the Akt signaling pathway, which in turn activates nuclear factor erythroid 2–related factor 2 (Nrf2) via phosphorylation, enhancing its stability and transcriptional activity. This pathway plays a critical role in mediating antioxidant defenses, suppressing inflammation, and inhibiting apoptosis. This study aimed to explore the potential neuroprotective role of ZNF655 in CIRI through modulation of the Akt/Nrf2 signaling cascade.

Methods

An in vitro model of CIRI was established using SH-SY5Y cells subjected to oxygen-glucose deprivation followed by reoxygenation (OGD/R). Cells were infected with adenoviral vector encoding ZNF655 to upregulate ZNF655 expression. The mRNA levels were measured by real-time quantitative PCR (RT-qPCR). Protein levels were determined by immunoblotting. Cell viability was assessed via cell counting kit-8 (CCK-8) assay. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Oxidative stress was monitored by dichlorofluorescein diacetate (DCFH-DA) probe. Inflammatory cytokine release was detected by enzyme-linked immunosorbent assay (ELISA).

Results

ZNF655 expression was significantly downregulated under OGD/R conditions compared with normoxic controls. Overexpression of ZNF655 markedly attenuated OGD/R-induced cell apoptosis, oxidative stress, and pro-inflammatory cytokine production. ZNF655 promoted Akt phosphorylation, facilitated Nrf2 nuclear translocation, and upregulated expression of downstream antioxidant genes.

Conclusion

Pharmacological inhibition of Akt or silencing of Nrf2 attenuated the neuroprotective effects of ZNF655. These findings indicate that ZNF655 exerts neuroprotective effects against OGD/R-induced injury by activating the Akt/Nrf2 signaling pathway.

背景：脑缺血再灌注损伤（CIRI）涉及复杂的病理过程，包括氧化应激、炎症反应和细胞凋亡。锌指蛋白655 （ZNF655）参与调控Akt信号通路，进而通过磷酸化激活核因子红系2相关因子2 (Nrf2)，增强其稳定性和转录活性。该通路在介导抗氧化防御、抑制炎症和抑制细胞凋亡中起关键作用。本研究旨在探讨ZNF655通过调节Akt/Nrf2信号级联在CIRI中的潜在神经保护作用。方法：采用SH-SY5Y细胞缺氧-葡萄糖剥夺-再氧合（OGD/R）法建立CIRI体外模型。用编码ZNF655的腺病毒载体感染细胞，上调ZNF655的表达。采用实时荧光定量PCR （RT-qPCR）检测mRNA水平。免疫印迹法测定蛋白水平。通过细胞计数试剂盒-8 （CCK-8）测定细胞活力。通过末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）评估细胞凋亡。采用双乙酸二氯荧光素（DCFH-DA）探针监测氧化应激。采用酶联免疫吸附试验（ELISA）检测炎症细胞因子释放。结果：与正常对照相比，OGD/R条件下ZNF655的表达明显下调。过表达ZNF655可显著减弱OGD/ r诱导的细胞凋亡、氧化应激和促炎细胞因子的产生。ZNF655促进Akt磷酸化，促进Nrf2核易位，上调下游抗氧化基因的表达。结论：药理抑制Akt或沉默Nrf2可减弱ZNF655的神经保护作用。这些结果表明，ZNF655通过激活Akt/Nrf2信号通路，对OGD/ r诱导的损伤具有神经保护作用。

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引用次数: 0