Brain Research最新文献_第6页

Modulation of face processing by top-down attention: Insights from early ERP waveforms 自上而下的注意力对人脸处理的调节：早期 ERP 波形的启示。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2024-10-02 DOI: 10.1016/j.brainres.2024.149258

The face fusiform area (FFA) plays a pivotal role in face recognition, yet the precise timeline of its activity remains debated. Using EEG, we conducted three experiments to investigate how expectancy-consistent versus expectancy-inconsistent visual stimuli influence processing dynamics. Participants viewed images of faces, houses, and tools (Experiment 1), celebrity faces (Experiment 2), or animal faces (Experiment 3), preceded by a priming question. Notably, both conditions presented identical visual stimulation, ensuring that observed differences stemmed from cognitive processing rather than sensory input. Our results from Experiments 2 and 3 reveal that while the initial 150 ms period, crucial for unconscious face detection, remained unaffected, subsequent processing exhibited a delay of several milliseconds for expectancy-inconsistent stimuli, indicating additional processing time required for unexpected recognition. Importantly, no significant differences were observed in Experiment 1, where less demanding tasks or generic mental imagery were used, suggesting that the priming effect was not as pronounced in this context. These findings underscore the critical role of the period immediately following the first 150 ms in face identification and individuation, highlighting the influence of top-down attention on face recognition dynamics. This study provides novel insights into the temporal dynamics of face processing and the neural mechanisms underlying top-down attentional modulation.

人脸纺锤区（FFA）在人脸识别中起着举足轻重的作用，但其活动的精确时间线仍存在争议。通过脑电图，我们进行了三项实验来研究期望一致与期望不一致的视觉刺激如何影响处理动态。受试者在观看人脸、房屋和工具的图像（实验 1）、名人的图像（实验 2）或动物的图像（实验 3）时，会先听到一个引申问题。值得注意的是，这两种情况都呈现了相同的视觉刺激，从而确保观察到的差异源于认知处理而非感官输入。实验 2 和实验 3 的结果表明，虽然对无意识人脸识别至关重要的最初 150 毫秒时间段未受影响，但对于预期不一致的刺激，后续处理却表现出几毫秒的延迟，这表明意外识别需要额外的处理时间。重要的是，在使用要求较低的任务或一般心理想象的实验 1 中没有观察到显著差异，这表明在这种情况下引物效应并不明显。这些发现强调了紧随第一个 150 毫秒之后的时间段在人脸识别和个体化中的关键作用，突出了自上而下的注意力对人脸识别动态的影响。这项研究为人脸加工的时间动态和自上而下注意调节的神经机制提供了新的见解。

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引用次数: 0

Clemastine enhances exercise-induced motor improvement in hypoxic ischemic rats 氯马斯汀能增强缺氧缺血大鼠运动引起的运动改善。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2024-10-01 DOI: 10.1016/j.brainres.2024.149257

Neonatal hypoxic ischemia (HI) occurs owing to reduced cerebral oxygen levels and perfusion during the perinatal period. Brain injury after HI triggers neurological manifestations such as motor impairment, and the improvement of impaired brain function remains challenging. Recent studies suggest that cortical myelination plays a role in motor learning, but its involvement in motor improvement after HI injury is not well understood. This study aimed to investigate the impact of myelination on motor improvement following neonatal HI injury. We employed a modified Rice-Vannucci model; the right common carotid artery of postnatal day 7 (P7) Wistar rats was isolated and divided, and the rats were then exposed to hypoxic condition (90 min, 8 % O2). A total of 101 rats (66 males) were divided into four groups: trained-HI (n = 38), trained-Sham (n = 16), untrained-HI (n = 31), and untrained-Sham (n = 16). The trained groups underwent rotarod-based exercise training from P22 to P41 (3 days per week). Structural analysis using magnetic resonance imaging and immunohistochemistry (n = 6 per group) revealed increased fractional anisotropy and myelin density in the primary somatosensory cortex of the trained-HI group. We further evaluated the effect of myelination promotion on rotarod performance by administering clemastine, a myelination-promoting drug, via daily intraperitoneal injections. Clemastine did not enhance motor improvement in untrained-HI rats. However, clemastine-administered trained-HI rats (n = 7) exhibited significantly improved motor performance compared to both saline-administered trained-HI rats (n = 11) and clemastine-administered untrained-HI rats (n = 7). These findings suggest that myelination may be a key mechanism in motor improvement after HI injury and that combining exercise training with clemastine administration could be an effective therapeutic strategy for motor improvement following HI injury.

新生儿缺氧缺血（HI）是由于围产期脑氧含量和灌注量减少而导致的。缺氧缺血后的脑损伤会引发运动障碍等神经系统表现，而改善受损的脑功能仍然具有挑战性。最近的研究表明，大脑皮层髓鞘化在运动学习中发挥作用，但其在脑损伤后运动功能改善中的作用尚不十分清楚。本研究旨在探讨髓鞘化对新生儿脑损伤后运动改善的影响。我们采用了改良的Rice-Vannucci模型；分离并分割出生后第7天（P7）Wistar大鼠的右侧颈总动脉，然后将大鼠暴露于缺氧条件下（90分钟，8 % O2）。总共 101 只大鼠（66 只雄性）被分为四组：训练-HI 组（38 只）、训练-Sham 组（16 只）、未训练-HI 组（31 只）和未训练-Sham 组（16 只）。训练组在 P22 至 P41 期间接受基于旋转木马的运动训练（每周 3 天）。利用磁共振成像和免疫组化技术进行的结构分析（每组 6 人）显示，训练有素的 HI 组初级躯体感觉皮层的分数各向异性和髓鞘密度增加。我们通过每天腹腔注射促进髓鞘化的药物氯马斯汀，进一步评估了促进髓鞘化对轮足表现的影响。氯马斯汀并不能提高未经训练的 HI 大鼠的运动能力。然而，与注射生理盐水的训练型脊髓灰质炎大鼠（n = 11）和注射氯马斯汀的未训练型脊髓灰质炎大鼠（n = 7）相比，注射氯马斯汀的训练型脊髓灰质炎大鼠（n = 7）的运动表现明显改善。这些研究结果表明，髓鞘化可能是脑损伤后运动能力改善的关键机制，将运动训练与氯马斯汀给药相结合可能是脑损伤后运动能力改善的有效治疗策略。

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引用次数: 0

Molecular profiling of a rat model of vascular dementia: Evidences from proteomics, metabolomics and experimental validations 大鼠血管性痴呆模型的分子剖析：蛋白质组学、代谢组学和实验验证的证据。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2024-09-26 DOI: 10.1016/j.brainres.2024.149254

Decrease of cerebral blood flow is the primary cause of vascular dementia (VD), but its pathophysiological mechanisms are still not known. This study aims to profile the molecular changes of a rat model of VD induced by bilateral common carotid artery ligation. The Morris water maze and new object recognition tasks were used to test the cognitive function of rats. Hematoxylin and Eosin (HE) staining was used to detect pathological changes in the hippocampus. After confirming the model, proteomics was used to detect differentially expressed proteins in the hippocampus, and metabolomics was used to detect differential metabolites in rat serum. Thereafter, bioinformatics were used to integrate and analyze the potential molecular profile. The results showed that compared with the sham control group, the spatial and recognition memory of the rats were significantly reduced, and pathological changes were observed in the hippocampal CA1 region of the model group. Proteomic analysis suggested 206 differentially expressed proteins in the hippocampus of VD rats, with 117 proteins upregulated and 89 downregulated. Protein-protein interaction network analysis suggested that those differentially expressed proteins might play crucial roles in lipid metabolism, cell adhesion, intracellular transport, and signal transduction. Metabolomics analysis identified 103 differential metabolites, and comparison with the human metabolome database revealed 22 common metabolites, which predicted 265 potential targets. Afterwards, by intersecting the predicted results from metabolomics with the differentially expressed proteins from proteomics, we identified five potential targets, namely ACE, GABBR1, Rock1, Abcc1 and Mapk10. Furthermore, western blotting confirmed that compared with control group, hippocampal GABBR1 and Rock1 were enhanced in the model group. Together, this study showed the molecular profile of VD rats through a combination of proteomics, metabolomics, and experimental confirmation methods, offering crucial molecular targets for the diagnosis and treatment of VD.

脑血流减少是血管性痴呆（VD）的主要病因，但其病理生理机制仍不清楚。本研究旨在剖析双侧颈总动脉结扎诱导的血管性痴呆大鼠模型的分子变化。研究采用 Morris 水迷宫和新物体识别任务测试大鼠的认知功能。血色素和伊红（HE）染色用于检测海马的病理变化。确认模型后，利用蛋白质组学检测海马中不同表达的蛋白质，并利用代谢组学检测大鼠血清中不同的代谢物。随后，生物信息学被用来整合和分析潜在的分子特征。结果显示，与假对照组相比，模型组大鼠的空间记忆和识别记忆明显减弱，海马CA1区出现病理变化。蛋白质组学分析表明，VD大鼠海马中有206个蛋白表达不同，其中117个蛋白上调，89个蛋白下调。蛋白质-蛋白质相互作用网络分析表明，这些差异表达的蛋白质可能在脂质代谢、细胞粘附、细胞内转运和信号转导中发挥关键作用。代谢组学分析发现了103种差异代谢物，与人类代谢组数据库比较发现了22种常见代谢物，预测出了265个潜在靶点。随后，通过将代谢组学的预测结果与蛋白质组学的差异表达蛋白进行交叉分析，我们确定了五个潜在靶点，分别是ACE、GABBR1、Rock1、Abcc1和Mapk10。此外，Western 印迹还证实，与对照组相比，模型组海马 GABBR1 和 Rock1 的表达增强。总之，本研究通过蛋白质组学、代谢组学和实验证实方法的结合，展示了VD大鼠的分子特征，为VD的诊断和治疗提供了重要的分子靶点。

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引用次数: 0

Remote ischemic conditioning slows blood-retinal barrier damage in type 1 diabetic rats 远程缺血调节可减缓 1 型糖尿病大鼠的血液-视网膜屏障损伤。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2024-09-25 DOI: 10.1016/j.brainres.2024.149253

Diabetic retinopathy (DR) is one of the major complications of diabetes and can cause severe visual impairment. Blood-retina barrier (BRB) destruction resulted from chronic hyperglycemia underlines its major pathological process. However, current treatments have limited efficacy and may even cause serious complications. Remote ischemic conditioning (RIC), through repeated transient mechanical occlusion of limb blood vessels, has been confirmed to promote blood–brain barrier integrity after stroke, but its role in BRB disruption has not been elucidated. This study aimed to investigate the protective effects of RIC on the BRB in diabetic rats and its potential mechanisms. 48 Sprague-Dawley rats were randomly assigned to the Sham group, Sham + RIC group, diabetes mellitus (DM) group and DM+RIC group. The diabetic model was successfully induced by intraperitoneal injection of streptozotocin. RIC treatment was administered daily and lasted for 9 weeks. In functional analysis, RIC improved the retinal function based on electroretinogram data and reduced the leakage of BRB in diabetic rats. In proteomic analysis, tight junction pathway was enriched after RIC treatment, in which Patj gene was significantly increased. We also found that RIC increased mRNA levels of Patj, claudin-1 and zonula occludens (ZO)-1, protein expression of claudin-1 when compared with diabetic models. In conclusion, RIC slowed BRB damage in diabetic rats, which may be related to the preservation of tight junction proteins. RIC may be a promising protective strategy for the treatment of DR.

糖尿病视网膜病变（DR）是糖尿病的主要并发症之一，可导致严重的视力损害。长期高血糖导致的血-视网膜屏障（BRB）破坏是其主要病理过程。然而，目前的治疗方法疗效有限，甚至可能引起严重的并发症。远程缺血调理（RIC）通过反复短暂机械性闭塞肢体血管，已被证实能促进卒中后血脑屏障的完整性，但其在血脑屏障破坏中的作用尚未阐明。本研究旨在探讨 RIC 对糖尿病大鼠血脑屏障的保护作用及其潜在机制。48 只 Sprague-Dawley 大鼠被随机分为 Sham 组、Sham + RIC 组、糖尿病（DM）组和 DM+RIC 组。腹腔注射链脲佐菌素（STZ）成功诱导出糖尿病模型。RIC 治疗每天进行，持续 9 周。在功能分析中，根据视网膜电图数据，RIC 改善了糖尿病大鼠的视网膜功能，并减少了 BRB 的渗漏。在蛋白质组学分析中，RIC 治疗后紧密连接通路富集，其中 Patj 基因显著增加。我们还发现，与糖尿病模型相比，RIC 增加了 Patj、claudin-1 和 zonula occludens (ZO)-1 的 mRNA 水平，以及 claudin-1 的蛋白表达。总之，RIC 可减缓糖尿病大鼠 BRB 的损伤，这可能与保护紧密连接蛋白有关。RIC可能是治疗DR的一种很有前景的保护策略。

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引用次数: 0

The role of trimethylation on histone H3 lysine 27 (H3K27me3) in temozolomide resistance of glioma 组蛋白 H3 赖氨酸 27 上的三甲基化（H3K27me3）在脑胶质瘤的替莫唑胺耐药性中的作用

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2024-09-24 DOI: 10.1016/j.brainres.2024.149252

Temozolomide (TMZ) is the first-line chemotherapeutic agent for malignant glioma, but its resistance limited the benefits of the treated patients. In this study, the role and significance of trimethylation of histone H3 lysine 27 (H3K27me3) in TMZ resistance were investigated. Data from twenty advanced glioma patients were collected, and their pathological samples were analyzed for H3K27me3 levels. TMZ sensitivity was compared between glioma cells U87 and TMZ-resistant cells U87TR, with H3K27me3 levels determined in both cells. The effects of H3K27me3 demethylases inhibitor GSK-J4, combined with TMZ, were assessed on the proliferation and migration of U87TR cells. The results indicated that a high level of H3K27me3 predicts longer disease free survival (DFS) and overall survival (OS) in glioma patients receiving TMZ treatment. The H3K27me3 level was lower in U87TR cells compared to U87 cells. GSK-J4 increased the H3K27me3 level in U87TR cells and decreased their resistance to TMZ. In summary, this study identified a novel marker of TMZ resistance in glioma and provided a new strategy to address this challenge. These findings are significant for improving the clinical treatment of glioma in the future.

替莫唑胺（TMZ）是治疗恶性胶质瘤的一线化疗药物，但其耐药性限制了患者的治疗效果。本研究探讨了组蛋白H3赖氨酸27的三甲基化（H3K27me3）在TMZ耐药性中的作用和意义。研究收集了20名晚期胶质瘤患者的数据，并对其病理样本的H3K27me3水平进行了分析。比较了胶质瘤细胞U87和TMZ耐药细胞U87TR对TMZ的敏感性，并测定了两种细胞的H3K27me3水平。评估了H3K27me3去甲基化酶抑制剂GSK-J4与TMZ联合使用对U87TR细胞增殖和迁移的影响。结果表明，高水平的H3K27me3可预测接受TMZ治疗的胶质瘤患者更长的无病生存期（DFS）和总生存期（OS）。与U87细胞相比，U87TR细胞的H3K27me3水平较低。GSK-J4提高了U87TR细胞的H3K27me3水平，降低了它们对TMZ的耐药性。总之，本研究发现了胶质瘤中TMZ耐药性的新标记物，并提供了应对这一挑战的新策略。这些发现对未来改善胶质瘤的临床治疗具有重要意义。

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引用次数: 0

Decreased SREBP2 of the striatal cell relates to disrupted protein degradation in Huntington’s disease 纹状体细胞中 SREBP2 的减少与亨廷顿氏病的蛋白质降解紊乱有关。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2024-09-21 DOI: 10.1016/j.brainres.2024.149250

This study delineated the intricate relation between cholesterol metabolism, protein degradation mechanisms, and the pathogenesis of Huntington’s disease (HD). Through investigations using both animal models and cellular systems, we have observed significant alterations in cholesterol levels, particularly in the striatum, which is the primary lesion site in HD. Our findings indicate the dysregulation of cholesterol metabolism-related factors, such as LDLR and SREBP2, in HD, which may contribute to disease progression. Additionally, we uncovered disruptions in protein degradation pathways, including decreased neddylated proteins and dysregulated autophagy, which further exacerbated HD pathology. Moreover, our study highlighted the potential therapeutic implications of targeting these pathways. By restoring cholesterol levels and modulating protein degradation mechanisms, particularly through interventions, such as MLN4924, we observed potential improvements in cellular function, as indicated by the increased BDNF levels. These insights underscore the importance of simultaneously addressing cholesterol metabolism and protein degradation to alleviate HD pathology. Collectively, this study provides a basic understanding of the interplay between the decrease of SREBP2 and the dysfunctional protein degradation system derived from disrupted cholesterol metabolism in HD and HD cells.

这项研究揭示了胆固醇代谢、蛋白质降解机制与亨廷顿氏病（HD）发病机制之间错综复杂的关系。通过使用动物模型和细胞系统进行研究，我们观察到胆固醇水平发生了显著变化，尤其是在纹状体中，而纹状体是 HD 的主要病变部位。我们的研究结果表明，胆固醇代谢相关因子（如 LDLR 和 SREBP2）在 HD 中的失调可能会导致疾病进展。此外，我们还发现了蛋白质降解途径的紊乱，包括内切酶蛋白减少和自噬失调，这进一步加剧了HD的病理变化。此外，我们的研究还强调了针对这些途径的潜在治疗意义。通过恢复胆固醇水平和调节蛋白质降解机制，特别是通过 MLN4924 等干预措施，我们观察到细胞功能的潜在改善，BDNF 水平的提高就表明了这一点。这些见解强调了同时解决胆固醇代谢和蛋白质降解问题以缓解 HD 病理学的重要性。总之，这项研究为我们提供了一个基本认识，即在 HD 和 HD 细胞中，SREBP2 的减少与胆固醇代谢紊乱导致的蛋白质降解系统功能失调之间的相互作用。

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引用次数: 0

Darts fast-learning reduces theta power but is not affected by Hf-tRNS: A behavioral and electrophysiological investigation 飞镖快速学习会降低θ功率，但不受 Hf-tRNS 的影响：一项行为学和电生理学研究。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2024-09-21 DOI: 10.1016/j.brainres.2024.149249

Sports trainers have recently shown increasing interest in innovative methods, including transcranial electric stimulation, to enhance motor performance and boost the acquisition of new skills during training. However, studies on the effectiveness of these tools on fast visuomotor learning and brain activity are still limited. In this randomized single-blind, sham-controlled, between-subjects study, we investigated whether a single training session, either coupled or not with 2 mA online high-frequency transcranial random noise stimulation (hf-tRNS) over the bilateral primary motor cortex (M1), would affect dart-throwing performance (i.e., radial error, arm range of motion, and movement variability) in 37 healthy volunteers. In addition, potential neurophysiological correlates were monitored before and after the training through a 32-electrode portable electroencephalogram (EEG). Results revealed that a single training session improved radial error and arm range of motion during the dart-throwing task, but not movement variability. Furthermore, after the training, resting state-EEG data showed a decrease in theta power. Radial error, arm movement, and EEG were not further modulated by hf-tRNS. This indicates that a single training session, regardless of hf-tRNS administration, improves dart-throwing precision and movement accuracy. However, it does not improve movement variability, which might require multiple training sessions (expertise resulting in slow learning). Theta power decrease could describe a more efficient use of cognitive resources (i.e., attention and visuomotor skills) due to the fast dart-throwing learning. Further research could explore different sports by applying longer stimulation protocols and evaluating other EEG variables to enhance our understanding of the lasting impacts of multi-session hf-tRNS on the sensorimotor cortex within the framework of slow learning and training assistance.

最近，体育教练对包括经颅电刺激在内的创新方法越来越感兴趣，这些方法可以在训练中提高运动表现并促进新技能的掌握。然而，有关这些工具对快速视觉运动学习和大脑活动有效性的研究仍然有限。在这项随机单盲、假对照、受试者之间的研究中，我们调查了单次训练是否会影响 37 名健康志愿者的掷镖表现（即弧度误差、手臂运动范围和运动变异性），这些训练是否与双侧初级运动皮层（M1）上的 2 毫安在线高频经颅随机噪声刺激（hf-tRNS）相结合。此外，还通过 32 个电极的便携式脑电图（EEG）对训练前后的潜在神经生理学相关因素进行了监测。结果显示，单次训练可减少投掷飞镖任务中的径向误差和手臂运动范围，但不能减少运动变异性。此外，训练后，静息状态脑电图数据显示θ功率下降。hf-tRNS 没有进一步调节径向误差、手臂运动和脑电图。这表明，无论服用何种 hf-tRNS 药物，单次训练都能提高投掷飞镖的精确度和动作准确性。然而，它并没有改善动作的可变性，而这可能需要多次训练（专业知识导致学习缓慢）。Theta 功率的降低可能说明由于快速学习投掷飞镖，认知资源（即注意力和视觉运动技能）得到了更有效的利用。进一步的研究可以通过应用更长的刺激方案和评估其他脑电图变量来探索不同的运动项目，从而在缓慢学习和训练辅助的框架内加深我们对多节 hf-tRNS 对感觉运动皮层的持久影响的理解。

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引用次数: 0

Chemical modulation of Akt signaling enhances spinal cord regeneration in zebrafish 化学调节 Akt 信号增强斑马鱼的脊髓再生能力

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2024-09-21 DOI: 10.1016/j.brainres.2024.149248

Central nervous system lesions often cause permanent motility defects in mammals since the injured neurons cannot regenerate. In contrast, lower vertebrates like zebrafish can regenerate lost neurons and restore motor function. This study investigates the efficacy of SC79, a pan-Akt activator, and A674563, a selective Akt1 inhibitor, as potential therapeutic agents for promoting spinal cord recovery post-injury. Spinal cord injury was induced in zebrafish larvae, and the effects of SC79 and A674563 on neuronal and glial regeneration were examined. SC79 promoted neuronal regeneration without affecting glial bridging, while A674563 induced glial bridging but reduced neuronal regeneration. The combination of SC79 and A674563 induced both glial bridging and neuronal regeneration. Optomotor response tests revealed improved motor function recovery with the combined treatment compared to individual treatments. Additionally, these chemical treatments altered the expression of 12 Akt downstream transcriptional target genes, affirming that the combination treatment preferentially regulates spinal cord regeneration through its action on Akt signaling. These findings highlight the complex interplay of Akt signaling pathways in spinal cord regeneration and suggest potential therapeutic strategies for enhancing functional recovery in spinal cord injury patients.

哺乳动物的中枢神经系统损伤通常会导致永久性运动缺陷，因为受伤的神经元无法再生。相比之下，斑马鱼等低等脊椎动物可以再生失去的神经元并恢复运动功能。本研究探讨了泛Akt激活剂SC79和选择性Akt1抑制剂A674563作为促进脊髓损伤后恢复的潜在治疗药物的功效。研究人员在斑马鱼幼体中诱导脊髓损伤，并考察了SC79和A674563对神经元和神经胶质再生的影响。SC79促进神经元再生，但不影响神经胶质桥接，而A674563诱导神经胶质桥接，但减少神经元再生。SC79 和 A674563 的组合既能诱导神经胶质桥接，又能促进神经元再生。视运动反应测试表明，与单独治疗相比，联合治疗能改善运动功能的恢复。此外，这些化学处理改变了 12 个 Akt 下游转录靶基因的表达，证实了联合处理通过对 Akt 信号的作用优先调节脊髓再生。这些发现凸显了Akt信号通路在脊髓再生过程中复杂的相互作用，并提出了增强脊髓损伤患者功能恢复的潜在治疗策略。

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引用次数: 0

Novel insights into the role of TREM2 in cerebrovascular diseases 关于 TREM2 在脑血管疾病中作用的新见解

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2024-09-19 DOI: 10.1016/j.brainres.2024.149245

Cerebrovascular diseases (CVDs) include conditions such as stroke, cerebral amyloid angiopathy (CAA) and cerebral small vessel disease (CSVD), which contribute significantly to global morbidity and healthcare burden. The pathophysiology of CVD is complex, involving inflammatory, cellular and vascular mechanisms. Recently, research has focused on triggering receptor expressed on myeloid cells 2 (TREM2), an immune receptor predominantly found on microglia. TREM2 interacts with multiple signalling pathways, particularly toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB), inhibiting patients’ inflammatory response. This receptor plays an essential role in both immune regulation and neuroprotection. TREM2 deficiency or dysfunction is associated with impaired microglial responses, exacerbated neurodegeneration and neuroinflammation. Up until recently, TREM2 related studies have focused on neurodegenerative diseases (NDs), however a shift in focus towards CVDs is beginning to take place. Advancements in CVD research have focused on developing therapeutic strategies targeting TREM2 to enhance recovery and reduce long-term deficits. These include the exploration of TREM2 agonists and combination therapies with other anti-inflammatory agents, which may synergistically reduce neuroinflammation and promote neuroprotection. The modulation of TREM2 activity holds potential for innovative treatment approaches aimed at improving patient outcomes following cerebrovascular insults. This review compiles current research on TREM2, emphasising its molecular mechanisms, therapeutic potential, and advancements in CNS disease research.

脑血管疾病（CVD）包括中风、脑淀粉样变性血管病（CAA）和脑小血管病（CSVD）等疾病，这些疾病在全球发病率和医疗负担中占很大比重。心血管疾病的病理生理学非常复杂，涉及炎症、细胞和血管机制。最近，研究重点放在髓系细胞上表达的触发受体 2（TREM2）上，这是一种主要存在于小胶质细胞上的免疫受体。TREM2 与多种信号通路相互作用，特别是与收费样受体 4（TLR4）和核因子卡巴 B（NF-κB）相互作用，从而抑制患者的炎症反应。该受体在免疫调节和神经保护中发挥着重要作用。TREM2 缺乏或功能障碍与小胶质细胞反应受损、神经退行性变加剧和神经炎症有关。直到最近，与 TREM2 相关的研究都集中在神经退行性疾病（NDs）上，但研究重点已开始转向心血管疾病。心血管疾病研究的进展主要集中在开发以 TREM2 为靶点的治疗策略，以促进康复并减少长期障碍。其中包括探索 TREM2 激动剂以及与其他抗炎药物的联合疗法，这可能会协同减少神经炎症并促进神经保护。通过调节 TREM2 的活性，有望采用创新的治疗方法，改善脑血管损伤后患者的预后。本综述汇编了目前有关 TREM2 的研究，强调了其分子机制、治疗潜力以及中枢神经系统疾病研究的进展。

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引用次数: 0

Caffeine intake during lactation has a sex-dependent effect on the hippocampal excitatory/inhibitory balance and pups’ behavior 哺乳期摄入咖啡因对海马兴奋/抑制平衡和幼崽行为的影响取决于性别。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2024-09-18 DOI: 10.1016/j.brainres.2024.149247

During early life, disruptions in glutamatergic and GABAergic synapse development in the hippocampus may contribute to several neurodevelopmental disorders, including cognitive deficits and psychiatric disorders. Caffeine is the most consumed psychoactive drug in the world, and previous work from our group has shown that caffeine disrupts visual system connections at different stages of development. This work aimed to investigate the effects of caffeine consumption during lactation in the glutamatergic and GABAergic synaptic markers in the hippocampus and on the behavior of rat offspring. We found that maternal caffeine intake significantly reduced GluN1 subunits of the NMDA receptor, increased the GluA1/GluA2 ratio of AMPA receptor in the dorsal hippocampus, and decreased GAD content in female pups’ ventral hippocampus. On the other hand, an increase in GluN1/GluN2b subunits, a decrease in GAD content in the dorsal hippocampus, and a reduction of the GluA1 content in the ventral hippocampus were observed in male pups. In addition, changes in the behavior of the offspring submitted to indirect caffeine consumption were also sex-dependent, with females developing anxiety-like behavior and males showing anxiety-like behavior and hyper-locomotion. These results highlight that maternal caffeine intake promotes changes in the hippocampal excitatory and inhibitory balance and offspring behavior in a sex-dependent manner, suggesting that the population should be alerted to reduced caffeine consumption by breastfeeding mothers.

在生命早期，海马中谷氨酸能突触和GABA能突触的发育中断可能会导致多种神经发育障碍，包括认知障碍和精神障碍。咖啡因是世界上消耗量最大的精神活性药物，我们小组之前的研究表明，咖啡因会破坏视觉系统在不同发育阶段的连接。这项工作旨在研究哺乳期摄入咖啡因对海马中谷氨酸能和 GABA 能突触标记的影响，以及对大鼠后代行为的影响。我们发现，母体摄入咖啡因会显著降低NMDA受体的GluN1亚单位，增加海马背侧AMPA受体的GluA1/GluA2比例，并降低雌性幼鼠海马腹侧的GAD含量。另一方面，在雄性幼鼠中观察到 GluN1/GluN2b 亚基增加，背侧海马中 GAD 含量减少，腹侧海马中 GluA1 含量减少。此外，间接摄入咖啡因后代的行为变化也与性别有关，雌性会出现焦虑样行为，雄性会出现焦虑样行为和过度运动。这些结果表明，母体摄入咖啡因会促进海马兴奋和抑制平衡以及后代行为的变化，而这种变化是性别依赖性的，这提示人们应警惕母乳喂养的母亲减少咖啡因的摄入量。

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