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Identification of potential inhibitors for MAP4K4 in glaucoma using Meta-Dynamics-Based dissociation free energy calculation. 利用基于元动力学的解离自由能计算,识别青光眼中 MAP4K4 的潜在抑制剂。
IF 2.7 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-03 DOI: 10.1016/j.brainres.2024.149300
Vanshika Rustagi, Rashmi Rameshwari, Indrakant Kumar Singh

Glaucoma, a prevalent eye ailment causing irreversible vision loss, affects over 295 million individuals globally, necessitating the exploration of novel therapeutic avenues. Despite extensive research on targets like the phosphodiesterase enzyme and rho kinase, the potential of MAP4K4 in glaucoma remains untapped. This study aims to identify potent MAP4K4 inhibitors to counteract retinal cell apoptosis and oxidative stress associated with glaucoma. Using HTVS and XP docking, 911,059 compounds were screened. The MMGBSA calculation and pharmacokinetics analysis were used to shortlist the compounds. After performing 75 molecular dynamics simulations, further meta-dynamics were employed to calculate dissociation-free energy and find potential MAP4K4 inhibitors. Findings indicated that ZINC06717217 and ZINC38836256 exhibited remarkable promise, with docking scores of -9.57 and -11.12 and MMGBSA binding energies of -91.07 kcal/mol and -87.52 kcal/mol, respectively. Comparative analysis with the reference compound Q27453723 underscored their superior stability, requiring dissociation-free energies of -15.11 kcal/mol and -12.46 kcal/mol to disengage from the docked complex. This underscored their robust binding affinity. ZINC06717217 and ZINC38836256 show promising stability and strong binding to the MAP4K4 protein. Hence, these findings are promising in inhibiting MAP4K4 for glaucoma treatment, potentially leading to more effective treatment and curing blindness. KEY MESSAGES: First to incorporate the dissociation-free energy for identifying compounds for glaucoma treatment. In-silico analysis showed that ZINC06717217 and ZINC38836256 are promising compounds for targeting MAP4K4.

青光眼是一种导致不可逆视力丧失的眼部常见疾病,全球有超过 2.95 亿人受到青光眼的影响,因此有必要探索新的治疗途径。尽管对磷酸二酯酶和 rho 激酶等靶点进行了广泛的研究,但 MAP4K4 在青光眼中的潜力仍有待开发。本研究旨在找出有效的 MAP4K4 抑制剂,以对抗与青光眼相关的视网膜细胞凋亡和氧化应激。通过 HTVS 和 XP docking,共筛选出 911,059 个化合物。利用 MMGBSA 计算和药代动力学分析筛选出化合物。在进行了 75 次分子动力学模拟后,进一步采用元动力学计算解离自由能,找到潜在的 MAP4K4 抑制剂。研究结果表明,ZINC06717217 和 ZINC38836256 的对接得分分别为 -9.57 和 -11.12,MMGBSA 结合能分别为 -91.07 kcal/mol 和 -87.52 kcal/mol,表现出显著的前景。与参比化合物 Q27453723 的比较分析表明,它们具有极高的稳定性,脱离对接复合物所需的无解离能分别为 -15.11 kcal/mol 和 -12.46 kcal/mol。这凸显了它们强大的结合亲和力。ZINC06717217 和 ZINC38836256 显示出良好的稳定性以及与 MAP4K4 蛋白的强结合力。因此,这些研究结果有望抑制 MAP4K4 以治疗青光眼,从而提高治疗效果并治愈失明。关键信息:首次将无离解能用于识别治疗青光眼的化合物。通过分子内分析发现,ZINC06717217 和 ZINC38836256 是有望靶向 MAP4K4 的化合物。
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引用次数: 0
Astrocytic Gap Junctions protein Cx43/Cx30 modulate EAAT1 and glutamate to mediate cerebral ischemia-reperfusion injury. 星形胶质细胞间隙连接蛋白Cx43/Cx30调节EAAT1和谷氨酸,介导脑缺血再灌注损伤
IF 2.7 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-02 DOI: 10.1016/j.brainres.2024.149306
Min Li, Hongxia Nie, Qianqian He, Zhaoting Zhang, Shanhua Yu, Tiantian Wang, Bing Fu

The gap connexins of astrocytes play a crucial role in facilitating neuronal coordination and maintaining the homeostasis of the central nervous system. Cx30/Cx43 are the main proteins constituting these gap junctions, and the glutamate transporter EAAT1 associates with nerve injury. However, the role and mechanism underlying the changes of astrocytic connexins and EAAT1 during cerebral ischemia-reperfusion injury remain unclear. In this study, we investigated the expressions of Cx30, Cx43, and EAAT1 in OGD/R-treated astrocytes and in a MCAO/R animal model using gap junction inhibitors and siRNAs targeting Cx43 and Cx30. The differences of cell viability, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reactive oxygen species (ROS) and glutamate in cells and tissues were detected. Our results indicate that OGD/R exposure leads to the decline of astrocyte activity, which, in turn, adversely affects neuronal health. Ischemia-reperfusion induced increasing Cx43 and EAAT1 expression and decreasing Cx30 expression in astrocytes and animal brain tissue. Moreover, ischemia-reperfusion resulted in heightened MDA and ROS levels and reduced CAT and SOD activities in both astrocytes and the surrounding brain tissue. The release of glutamate from astrocytes and its concentration in animal brain tissue significantly increased following ischemia-reperfusion. Inhibition Cx43 expression through Gap26 or siRNA effectively mitigated the increase in EAAT1 and glutamate levels, as well as the oxidative stress changes induced by ischemia-reperfusion. Therefore, Brain astrocytes may mediate the effects of cerebral ischemia-reperfusion injury by influencing glutamate transporters and glutamate dynamics in response to oxidative stress through Cx30/Cx43.

星形胶质细胞的间隙连接蛋白在促进神经元协调和维持中枢神经系统平衡方面发挥着至关重要的作用。Cx30/Cx43 是构成这些间隙连接的主要蛋白,谷氨酸转运体 EAAT1 与神经损伤有关。然而,脑缺血再灌注损伤期间星形胶质细胞连接蛋白和 EAAT1 变化的作用和机制仍不清楚。在这项研究中,我们使用间隙连接抑制剂和靶向 Cx43 和 Cx30 的 siRNA 研究了 OGD/R 处理的星形胶质细胞和 MCAO/R 动物模型中 Cx30、Cx43 和 EAAT1 的表达。我们检测了细胞和组织中细胞活力、丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、活性氧(ROS)和谷氨酸的差异。我们的研究结果表明,OGD/R 暴露会导致星形胶质细胞活性下降,进而对神经元健康产生不利影响。缺血再灌注诱导星形胶质细胞和动物脑组织中的 Cx43 和 EAAT1 表达增加,Cx30 表达减少。此外,缺血再灌注导致星形胶质细胞和周围脑组织中的 MDA 和 ROS 水平升高,CAT 和 SOD 活性降低。缺血再灌注后,星形胶质细胞释放的谷氨酸及其在动物脑组织中的浓度显著增加。通过 Gap26 或 siRNA 抑制 Cx43 的表达能有效缓解 EAAT1 和谷氨酸水平的增加,以及缺血再灌注引起的氧化应激变化。因此,脑星形胶质细胞可能通过Cx30/Cx43影响谷氨酸转运体和谷氨酸的动态变化以应对氧化应激,从而介导脑缺血再灌注损伤的影响。
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引用次数: 0
Altered callosal morphology in post stroke cognitive impairment. 中风后认知障碍中的胼胝体形态改变。
IF 2.7 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-02 DOI: 10.1016/j.brainres.2024.149307
Xiaoli Zhou, Huan Li, Tao Li, Zhao Ruan, Xiaohui Chen, Xitong Liu, Lei Gao, Haibo Xu

Stroke is the second leading cause of death and cognitive impairment. Post-stroke cognitive impairment (PSCI) is one of the most common sequelae among stroke survivors, yet its underlying neural mechanisms remain largely unclear. The corpus callosum (CC) plays a crucial role in interhemispheric integration and hemispheric segregation, with changes in CC morphology potentially overlapping with the spectrum of PSCI. This study aimed to investigate the morphological changes in the CC and their diagnostic value in PSCI patients. Structural MRI, neurobehavioral, and clinical data were collected from 104 PSCI patients and 54 demographically matched healthy controls. Significant reductions in CC area, circularity, and genu thickness were observed in PSCI patients, with these changes strongly correlating with global cognitive function. Subgroup analysis revealed that CC circularity significantly decreased when lesions were located in the posterior circulation, while both CC area and circularity markedly decreased with anterior circulation lesions. Receiver Operating Characteristic analyses identified the midbody areas of the CC as having high diagnostic value, with area under the curve values of 0.748 and 0.746, respectively. Further validation analyses suggest that the transcallosal fibers in these CC subregions are connected to the premotor, dorsal attention, and frontoparietal system. These findings show that areal CC atrophy in PSCI patients, particularly in regions with transcallosal connections to the premotor cortex and frontoparietal network, parallels global cognitive impairment. This suggests that CC morphology may serve as a potential imaging marker for the diagnosis and prognosis of PSCI.

中风是导致死亡和认知障碍的第二大原因。脑卒中后认知障碍(PSCI)是脑卒中幸存者最常见的后遗症之一,但其潜在的神经机制在很大程度上仍不清楚。胼胝体(CC)在半球间整合和半球分离中起着至关重要的作用,CC形态学的变化可能与PSCI的范围重叠。本研究旨在探讨CC的形态学变化及其在PSCI患者中的诊断价值。研究收集了104名PSCI患者和54名人口统计学匹配的健康对照者的结构磁共振成像、神经行为和临床数据。在PSCI患者中观察到CC面积、圆度和真皮厚度显著减少,这些变化与整体认知功能密切相关。亚组分析显示,当病变位于后循环时,CC的圆度明显下降,而当病变位于前循环时,CC面积和圆度均明显下降。接收者操作特征分析表明,CC的中体区域具有很高的诊断价值,其曲线下面积值分别为0.748和0.746。进一步的验证分析表明,这些CC亚区的跨胼胝体纤维与前运动、背侧注意和顶叶前部系统相连。这些研究结果表明,PSCI 患者的 CC 肢体萎缩,尤其是在与前运动皮层和额顶叶网络有跨胼胝体连接的区域,与整体认知障碍并行。这表明,CC形态学可作为诊断和预后PSCI的潜在影像标记。
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引用次数: 0
Pathophysiology of cerebral ischemia-reperfusion injury: An overview of oxidative stress and plant-based therapeutic approaches. 脑缺血再灌注损伤的病理生理学:氧化应激和植物治疗方法概述。
IF 2.7 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-02 DOI: 10.1016/j.brainres.2024.149308
Wasim Akhtar, Mohd Muazzam Khan, Sanjay Kumar, Usama Ahmad, Ali Husen, Shiirevnyamba Avirmed

Stroke is a debilitating neurological disorder that causes substantial morbidity and mortality on a global scale. Ischemic stroke, the most common type, occurs when the brain's blood supply is interrupted. Oxidative stress is a key factor in stroke pathology, contributing to inflammation and neuronal cell death. As a result, there is increasing interest in the potential of plant extracts, which have been used in traditional medicine for centuries and are generally considered safe, to serve as alternative or complementary treatments for stroke. The plant extracts can target multiple pathological processes, including oxidative stress, offering neuroprotective effects. The development of highly efficient, low-toxicity, and cost-effective natural products is crucial for enhancing stroke treatment options. In this review, we examine 60 plant extracts that have been focused on the studies published from year 2000 to 2024 along with the studies' experimental models, dosages, and results. The plant extracts hold promise in modulating cerebral ischemia-reperfusion injury through counteraction of relevant pathophysiologic processes such as oxidative stress.

中风是一种使人衰弱的神经系统疾病,在全球范围内造成大量的发病和死亡。缺血性中风是最常见的类型,发生时大脑供血中断。氧化应激是中风病理的一个关键因素,会导致炎症和神经细胞死亡。因此,人们越来越关注植物萃取物作为中风替代或辅助疗法的潜力,因为植物萃取物在传统医学中已使用了几个世纪,而且被普遍认为是安全的。植物提取物可针对多种病理过程,包括氧化应激,提供神经保护作用。开发高效、低毒、成本效益高的天然产品对提高中风治疗效果至关重要。在这篇综述中,我们对 2000 年至 2024 年间发表的 60 项植物提取物研究进行了重点研究,并对研究的实验模型、剂量和结果进行了分析。这些植物提取物有望通过对抗氧化应激等相关病理生理过程来调节脑缺血再灌注损伤。
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引用次数: 0
Intact ultrafast memory consolidation in adults with autism and neurotypicals with autism traits. 成人自闭症患者和具有自闭症特征的神经类型患者的完整超快速记忆巩固。
IF 2.7 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-10-30 DOI: 10.1016/j.brainres.2024.149299
Cintia Anna Nagy, Flóra Hann, Bianka Brezóczki, Kinga Farkas, Teodóra Vékony, Orsolya Pesthy, Dezső Németh

The processes of learning and memory consolidation are closely interlinked. Therefore, to uncover statistical learning in autism spectrum disorder (ASD), an in-depth examination of memory consolidation is essential. Studies of the last five years have revealed that learning can take place not only during practice but also during micro (<1 min) rests between practice blocks, termed micro offline gains. The concept of micro offline gains refers to performance improvements during short rest periods interspersed with practice, rather than during practice itself. This phenomenon is crucial for the acquisition and consolidation of motor skills and has been observed across various learning contexts. Numerous studies on learning in autism have identified intact learning but there has been no investigation into this fundamental aspect of memory consolidation in autistic individuals to date. We conducted two studies with two different samples: 1) neurotypical adults with distinct levels of autistic traits (N = 166) and 2) ASD-diagnosed adults (nASD = 22, nNTP = 20). Participants performed a well-established probabilistic learning task, allowing us to measure two learning processes separately in the same experimental design: statistical learning (i.e., learning probability-based regularities) and visuomotor performance (i.e., speed-up regardless of probabilities). Here we show considerable individual differences in offline (between blocks) changes during statistical learning and between-blocks improvement during visuomotor performance. However, cumulative evidence from individual studies suggests that the degree of autistic traits and ASD status are not associated with micro offline gains, suggesting that, like statistical learning, rapid memory consolidation is intact.

学习过程与记忆巩固密切相关。因此,要揭示自闭症谱系障碍(ASD)的统计学习,就必须对记忆巩固进行深入研究。过去五年的研究表明,学习不仅可以在练习过程中进行,也可以在微观过程中进行(ASD = 22,nNTP = 20)。受试者完成了一项成熟的概率学习任务,这使我们能够在同一实验设计中分别测量两个学习过程:统计学习(即学习基于概率的规律性)和视觉运动表现(即加速而不考虑概率)。在这里,我们发现在统计学习过程中的离线(区块间)变化和视觉运动表现过程中的区块间改进方面存在着相当大的个体差异。然而,来自个别研究的累积证据表明,自闭症特征的程度和自闭症状态与微观离线收益无关,这表明,与统计学习一样,快速记忆巩固也是完好无损的。
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引用次数: 0
Annexin A5 derived from lung alleviates brain damage after ischemic stroke. 源自肺部的附录蛋白 A5 可减轻缺血性中风后的脑损伤。
IF 2.7 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-10-29 DOI: 10.1016/j.brainres.2024.149303
Jiaxin Hu, Jiaqi Guo, Chuanjie Wu, Xiaoduo He, Jian Jing, Meimei Tao

Ischemic stroke is a leading cause of disability and death worldwide. It is now accepted that brain interacts bidirectionally with other organs after brain diseases. However, factors that might mediate crosstalk between brain and other organs are still less reported. Here we reported that plasma level of Annexin A5, not Annexin A1 or A2, was upregulated in stroke patients when compared to controls. In normal mice, the highest levels of Annexin A5 were detected in lung tissues compared with other major organs and lowest level in brain. Moreover, Annexin A5 was increased in brain and decreased in lung after stroke in mice when compared to sham group. Fluorescence in situ hybridization (FISH) assay indicated that Annexin A5 could penetrate the blood-brain barrier (BBB). Treatment with Annexin A5 recombinant protein reduced the infarct volumes and improved neurological function after stroke in mice, while administration of anti-Annexin A5 increased the infarct sizes and aggravated neurological function. In a proof-of-concept analysis, patients with both ischemic stroke and lung diseases had a lower plasma Annexin A5 level than those with only ischemic stroke. Furthermore, Annexin A5 level in bronchoalveolar lavage fluid (BALF) was lower in patients with severe chronic obstructive pulmonary disease (COPD) when compared with those at a less severe grade of COPD, and level of Annexin A5 was positively correlated with forced expiratory volume in 1 s (FEV1) and PaO2. Our results suggest that Annexin A5 could alleviate infarct area and improve general neurological performance post cerebral ischemia. Increased Annexin A5 may derive from lung tissue and permeate across BBB to provide a neuroprotective function. Therefore, Annexin A5 may potentially serve as a therapeutic candidate for defending against IS-induced brain injury.

缺血性中风是全球致残和致死的主要原因。脑部疾病发生后,大脑与其他器官之间的双向互动已被公认。然而,可能介导脑与其他器官之间相互影响的因素仍鲜有报道。在此,我们报告了与对照组相比,脑卒中患者血浆中的附件蛋白 A5(而非附件蛋白 A1 或 A2)水平上调。在正常小鼠中,与其他主要器官相比,肺组织中的附件蛋白 A5 水平最高,而脑中的水平最低。此外,与假组相比,脑卒中后小鼠脑中的 Annexin A5 增加,肺中的 Annexin A5 减少。荧光原位杂交(FISH)检测表明,Annexin A5可穿透血脑屏障(BBB)。用Annexin A5重组蛋白治疗可缩小小鼠中风后的梗死体积并改善神经功能,而服用抗Annexin A5则会扩大梗死体积并加重神经功能。在概念验证分析中,缺血性中风和肺部疾病患者的血浆附件蛋白 A5 水平低于仅患有缺血性中风的患者。此外,严重慢性阻塞性肺病(COPD)患者支气管肺泡灌洗液(BALF)中的 Annexin A5 含量低于病情较轻的慢性阻塞性肺病患者,且 Annexin A5 含量与 1 秒用力呼气容积(FEV1)和 PaO2 呈正相关。我们的研究结果表明,Annexin A5可减轻脑缺血后的梗死面积并改善一般神经功能表现。增加的Annexin A5可能来自肺组织并通过BBB渗透,从而提供神经保护功能。因此,Annexin A5 有可能成为抵御 IS 引起的脑损伤的候选疗法。
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引用次数: 0
Synergistic interaction between clonidine and ACPA on the modulation of anxiety-like behaviors in non-acute restraint stress and acute restraint stress conditions. 在非急性束缚应激和急性束缚应激条件下,氯尼丁和ACPA对焦虑样行为的调节具有协同作用。
IF 2.7 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-10-29 DOI: 10.1016/j.brainres.2024.149304
Amir Chitsaz, Mohaddeseh Ebrahimi-Ghiri, Mohammad-Reza Zarrindast, Fatemeh Khakpai

The present research examined the possible role of α-2 adrenergic receptor drugs (clonidine, selective α-2 adrenergic receptor agonist, and yohimbine, competitive α-2 adrenoreceptor antagonist,) on the effect of arachidonylcyclopropylamide (ACPA), a cannabinoid CB1 receptor agonist, in non-acute restraint stress (NARS) and acute restraint stress (ARS) mice. The animals were unilaterally implanted with a cannula in the left lateral ventricle. ARS was carried out by movement restraint at a period of 4 h. An elevated plus-maze (EPM) apparatus was used to evaluate anxiety-like behaviors. The results indicated that induction of ARS for 4 h induced anxiogenic-like behavior due to the reduction of %OAT (the percentage of time spent in the open arms) in male mice. Additionally, ARS caused neuronal degeneration in the prefrontal cortex. On the other hand, alone intracerebroventricularly (i.c.v.) infusions of ACPA (0.5 µg/mouse) and clonidine (0.5 µg/mouse) increased %OAT, indicating an anxiolytic-like response in the NARS and ARS mice. In contrast, alone i.c.v. infusions of yohimbine (0.5 µg/mouse) decreased %OAT and %OAE (the percentage of entries to the open arms), proposing an anxiogenic-like effect in the NARS and ARS mice. When the subthreshold dose of ACPA and different doses of clonidine were co-injected, ACPA potentiated the anxiolytic-like behavior produced by clonidine in the ARS mice. On the other hand, when the ineffective dosage of ACPA and different dosages of yohimbine were co-infused, ACPA reversed the anxiogenic-like effect induced by yohimbine in the NARS and ARS mice. Moreover, the results revealed a synergistic effect between ACPA and clonidine upon induction of anxiolytic-like behaviors. It can be concluded that the interaction between clonidine and ACPA modulates the anxiety-like behaviors induced by stress in male mice.

本研究探讨了α-2肾上腺素能受体药物(氯尼丁,选择性α-2肾上腺素能受体激动剂;育亨宾,竞争性α-2肾上腺素受体拮抗剂)对非急性束缚应激(NARS)和急性束缚应激(ARS)小鼠体内大麻素CB1受体激动剂花生四烯醇环丙基酰胺(ACPA)效应的可能作用。小鼠单侧左心室植入插管。急性束缚应激是通过4小时的运动束缚进行的。高架迷宫(EPM)装置用于评估焦虑样行为。结果表明,诱导4小时的ARS会导致雄性小鼠的%OAT(张开双臂的时间百分比)降低,从而诱发焦虑样行为。此外,ARS 还会导致前额叶皮层神经元退化。另一方面,单独脑室内注射ACPA(0.5微克/只小鼠)和氯尼丁(0.5微克/只小鼠)会增加OAT%,这表明NARS和ARS小鼠有类似抗焦虑的反应。与此相反,单独静注育亨宾(0.5 µg/只小鼠)会降低OAT%和OAE%(进入开放臂的百分比),这表明对NARS和ARS小鼠有致焦虑样效应。当同时注射阈下剂量的 ACPA 和不同剂量的氯尼替丁时,ACPA 会增强氯尼替丁在 ARS 小鼠中产生的抗焦虑样行为。另一方面,当无效剂量的ACPA和不同剂量的育亨宾同时注射时,ACPA能逆转育亨宾在NARS和ARS小鼠中诱导的致焦虑样效应。此外,研究结果表明,ACPA 和氯尼丁在诱导抗焦虑样行为方面具有协同作用。由此可以得出结论:氯尼丁和 ACPA 之间的相互作用可调节应激对雄性小鼠诱发的焦虑样行为。
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引用次数: 0
Frontal alpha and parietal theta asymmetries associated with color-induced emotions 与颜色诱发情绪相关的额叶α和顶叶θ不对称。
IF 2.7 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-10-28 DOI: 10.1016/j.brainres.2024.149297
This study investigates the relationship between color perception—hue, brightness, and saturation—and its emotional response—valence, arousal, and pleasure—, through subjective evaluations, as well as their association with frontal and parietal asymmetric activity patterns through electroencephalographic (EEG) recording. Using the 37 colors from the Berkeley Color Project, along with positive and negative control images, we examined the perceptual and emotional dimensions of color in 32 Mexican participants (19 women; M = 21.4 years, SD = 3.3). Subjective evaluations revealed a strong positive correlation between valence and brightness, and between arousal and saturation. Brighter, arousing, and pleasant colors were associated with greater cortical activation (decreased alpha power) in the left dorsolateral prefrontal region—i.e., F3 electrode—, indicating positive emotional processing according to the frontal alpha asymmetry model. Additionally, increased theta power in the right lateral parietal region—i.e., P4 electrode—correlated with higher positive emotional and pleasurable responses. Our findings are in line with studies suggesting universal consistencies in how perceptual color dimensions relate to emotional responses. Moreover, significant correlations between subjective emotional responses and asymmetrical EEG activity models are highlighted, providing insights into the neural mechanisms of color-induced emotion perception, as no other study has done before to our knowledge. Further research should explore these associations using higher spatial resolution imaging techniques and larger electrode arrays to define precise cortical and subcortical regions involved. These results contribute to understanding color perception’s impact on emotions, with potential applications in mental health treatments, such as chromotherapy for mood disorders.
本研究通过主观评价研究了色彩感知--色调、亮度和饱和度--与情绪反应--愉悦、兴奋和愉悦之间的关系,并通过脑电图(EEG)记录研究了色彩感知与额叶和顶叶不对称活动模式之间的关联。我们使用伯克利色彩项目中的 37 种颜色以及正负对照图像,研究了 32 名墨西哥参与者(19 名女性;中位数 = 21.4 岁,标准差 = 3.3)对色彩的感知和情感维度。主观评价显示,情感与亮度、唤醒与饱和度之间存在很强的正相关性。明亮、唤醒和愉悦的颜色与左侧背外侧前额叶区域--即 F3 电极--更强的皮层激活(α 功率下降)有关,根据额叶α 不对称模型,这表明情绪处理是积极的。此外,右侧顶叶区(即 P4 电极)θ 功率的增加与较高的积极情绪和愉悦反应相关。我们的研究结果表明,感知颜色维度与情绪反应的关系具有普遍一致性。此外,主观情绪反应与非对称脑电活动模型之间的重要相关性也得到了强调,这为我们深入了解颜色诱发情绪感知的神经机制提供了线索,据我们所知,此前还没有其他研究做过这样的研究。进一步的研究应使用更高的空间分辨率成像技术和更大的电极阵列来探索这些关联,以精确界定所涉及的皮层和皮层下区域。这些结果有助于理解色彩感知对情绪的影响,并有可能应用于心理健康治疗,如治疗情绪障碍的色疗。
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引用次数: 0
Intermittent hypoxia-hyperoxia training ameliorates cognitive impairment and neuroinflammation in a rat model of Alzheimer's disease. 间歇性缺氧-过氧训练可改善阿尔茨海默病大鼠模型的认知障碍和神经炎症。
IF 2.7 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-10-28 DOI: 10.1016/j.brainres.2024.149301
Zoya Serebrovska, Lei Xi, Mykhailo Fedoriuk, Victor Dosenko, Angela Shysh, Michael Khetsuriani, Denys Porkhalo, Anton Savchenko, Serhii Goncharov, Natalie Utko, Sergii Virko, Victor Kholin, Egor Egorov, Roman Koval, Oksana Maksymchuk

Alzheimer's disease (AD), characterized by severe and progressive cognitive decline, stands as one of the most prevalent and devastating forms of dementia. Based on our recent findings showing intermittent hypoxic conditioning improved neuronal function in patients with mild cognitive impairment, the present study aimed at investigating whether the neuroprotective effects of intermittent hypoxia can be replicated in a rat model of AD, which allows us to explore the underlying cellular mechanisms involving neuroinflammation, hypoxia inducible factor 1α (HIF1α), and cytochrome P450 family 2 subfamily E member 1 (CYP2E1). Forty-one adult male Wistar rats were randomly assigned to three groups: 1) Control group: received intracerebroventricular (ICV) injection of saline; 2) STZ group: received ICV injection of streptozotocin (STZ) to induce AD-like pathology; and 3) STZ + IHHT group received ICV injection of STZ as well as 15 daily sessions of intermittent hypoxia-hyperoxia training (IHHT). We observed that ICV injection of STZ inhibited spatial learning and memory in the rats assessed with Morris Water Maze test. The cognitive function declines were accompanied by increased expression of amyloid β peptide (Aβ), HIF1α, CYP2E1, and TNFα in hippocampus. Interestingly, IHHT significantly restored the STZ-induced cognitive dysfunction, while reduced expression of Aβ, CYP2E1, HIF1α and TNFα. We conclude that IHHT with mild hypoxia-hyperoxia can enhance spatial learning and memory and reduce the AD-like pathologic changes in rats. The neuroprotective outcome of IHHT may be related to anti-inflammatory effects in hippocampus.

阿尔茨海默病(AD)以严重和进行性认知功能衰退为特征,是最常见和最具破坏性的痴呆症之一。基于我们最近的研究结果表明间歇性缺氧调节能改善轻度认知障碍患者的神经元功能,本研究旨在探讨间歇性缺氧的神经保护作用是否能在阿尔茨海默病大鼠模型中复制,从而探索涉及神经炎症、缺氧诱导因子1α(HIF1α)和细胞色素P450家族2亚家族E成员1(CYP2E1)的潜在细胞机制。将41只成年雄性Wistar大鼠随机分为三组:1)对照组:脑室内注射生理盐水;2)STZ组:脑室内注射链脲佐菌素(STZ)诱导AD样病理;3)STZ + IHHT组:脑室内注射STZ,同时每天进行15次间歇性缺氧-过氧训练(IHHT)。我们观察到,ICV注射STZ抑制了大鼠的空间学习和记忆能力。认知功能的下降伴随着海马中淀粉样β肽(Aβ)、HIF1α、CYP2E1和TNFα表达的增加。有趣的是,IHHT能明显恢复STZ诱导的认知功能障碍,同时降低Aβ、CYP2E1、HIF1α和TNFα的表达。我们的结论是,轻度缺氧-过氧的IHHT能增强大鼠的空间学习和记忆能力,减少AD样病理改变。IHHT的神经保护作用可能与海马的抗炎作用有关。
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引用次数: 0
Lindera aggregata improves intestinal function and alleviates depressive behaviors through the BDNF/TrkB/CREB signaling pathway induced by CUMS in mice Lindera aggregata 可通过 CUMS 诱导的 BDNF/TrkB/CREB 信号通路改善小鼠肠道功能并缓解抑郁行为
IF 2.7 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-10-28 DOI: 10.1016/j.brainres.2024.149295
Depression is a common mental illness, which is highly related to intestinal motor dysfunction and causes a global burden of disease. Lindera aggregata (LA), a traditional medicinal herb, has been used to treat gastrointestinal disorders; however, the effect of LA on depression remains unclear. Here, we assessed the impact of LA on chronic unpredictable mild stress (CUMS)-induced depression in mice and explored the related mechanisms. The results showed that LA ameliorated depressive behaviors in mice exposed to CUMS, as evidenced by improved performance in the sucrose preference test, force swimming test, and open field test, as well as increased serum levels of adrenocorticotropic hormone and 5-hydroxytryptamine. In addition, LA increased the serum levels of D-xylose and ghrelin, indicating that LA can promote gastrointestinal motility. Additional studies revealed that LA relieved CUMS-induced hippocampal tissue damage, as shown by hematoxylin and eosin and Nissl staining. LA increased the expression levels of brain-derived neurotrophic factor (BDNF) and promoted the activation of tropomyosin receptor kinase B (TrkB) and cAMP response element-binding (CREB) in the hippocampus of CUMS-exposed mice or in corticosterone-injured HT22 cells. In conclusion, LA can improve CUMS-induced depressive behavior in mice, potentially through hippocampal neuroprotection mediated by the BDNF/TrkB/CREB signaling pathway, which also contributes to improved intestinal function.
抑郁症是一种常见的精神疾病,与肠道运动功能障碍密切相关,并造成全球疾病负担。Lindera aggregata(LA)是一种传统草药,被用于治疗胃肠道疾病;然而,LA对抑郁症的影响仍不清楚。在此,我们评估了LA对慢性不可预测轻度应激(CUMS)诱导的小鼠抑郁症的影响,并探讨了相关机制。结果表明,LA能改善CUMS小鼠的抑郁行为,表现在蔗糖偏好试验、用力游泳试验和开阔地试验中的表现有所改善,血清中促肾上腺皮质激素和5-羟色胺的水平也有所提高。此外,LA还能提高血清中D-木糖和胃泌素的水平,表明LA能促进胃肠道蠕动。其他研究表明,LA 可缓解 CUMS 引起的海马组织损伤,苏木精、伊红和 Nissl 染色均显示了这一点。在暴露于 CUMS 的小鼠海马或皮质酮损伤的 HT22 细胞中,LA 提高了脑源性神经营养因子(BDNF)的表达水平,并促进了肌球蛋白受体激酶 B(TrkB)和 cAMP 反应元件结合(CREB)的活化。总之,LA 可以改善 CUMS 诱导的小鼠抑郁行为,这可能是通过 BDNF/TrkB/CREB 信号通路介导的海马神经保护作用实现的,该作用还有助于改善肠道功能。
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Brain Research
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