Brain Research最新文献_第6页

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

An organ-on-a-chip investigation into dose-dependent, temporal dynamic effects of radiosurgery on the blood–brain barrier and its immunological response 一项器官芯片研究放射手术对血脑屏障及其免疫反应的剂量依赖性、时间动态效应

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-04 DOI: 10.1016/j.brainres.2025.150092

Adam D. Yock , Jacquelyn A. Brown , John Eley , Cara Lwin , Dandan Liu , John P. Wikswo

Purpose

This work used an organ-on-a-chip (OOC) model of the blood–brain barrier (BBB) to study effects of clinical radiation on barrier permeability and cytokine concentrations.

Methods

Gravity-perfused OOC devices developed in house for modeling the BBB were prepared with human endothelial cells, astrocytes, and pericytes. The devices were then irradiated to 0, 2, or 20 Gy with a 6 MV X-ray beam from a medical linear accelerator. At 0, 6, 24, and 48 h post irradiation, barrier permeability was assessed by measuring the diffusion across the barrier of Alexa Fluor-labeled dextran perfused into the vascular chamber. At these same time points, effluent was drawn from both the vascular and brain chambers and analyzed using a 10-cytokine panel.

Results

A statistically significant increase in barrier permeability was observed at 24 and 48 h and appeared similar between 2 and 20 Gy. For 20 Gy but not 2 Gy, a large initial increase was observed in the concentration of Granulocyte-Macrophage Colony-Stimulating Factor in the vascular chamber at 6 h, which subsequently decreased. An increase was also observed in the concentration of Interleukin-1α in the brain chamber starting at 24 h and continuing to 48 h. The concentration of Vascular Endothelial Growth Factor was observed to increase starting at 6 h and 24 h in the vascular chamber and brain chamber, respectively, and to subsequently decrease in both chambers.

Conclusions

Radiation effects on the BBB including barrier permeability and cytokine concentration can be observed in a dose- and time-dependent manner using an OOC.

目的建立血脑屏障（BBB）器官芯片（OOC）模型，研究临床放疗对血脑屏障通透性和细胞因子浓度的影响。方法以人内皮细胞、星形胶质细胞和周细胞为材料，制备自行研制的用于血脑屏障建模的重力灌注OOC装置。然后用来自医用直线加速器的6 MV x射线束照射到0、2或20 Gy。在照射后0、6、24和48小时，通过测量灌注到血管室的Alexa荧光标记葡聚糖在屏障上的扩散来评估屏障通透性。在这些相同的时间点，从血管室和脑室抽取流出物，并使用10-细胞因子面板进行分析。结果24和48 h时屏障通透性增加，2和20 Gy时相似。当剂量为20 Gy而非2 Gy时，血管腔内粒细胞-巨噬细胞集落刺激因子浓度在6 h时开始大幅上升，随后下降。脑腔内白细胞介素-1α浓度从24小时开始升高，并持续到48小时。血管内皮生长因子浓度分别从6小时和24小时开始在血管腔和脑腔中升高，随后在两个腔中均下降。结论使用OOC可以观察辐射对血脑屏障的影响，包括屏障通透性和细胞因子浓度，并具有剂量和时间依赖性。

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引用次数: 0

Spatiotemporal profiling of endocytic regulators in the immunosuppressive TAM microenvironment of glioma 脑胶质瘤免疫抑制TAM微环境中内吞调节因子的时空特征分析。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-04 DOI: 10.1016/j.brainres.2025.150086

Shi Hua , Yanhao Cheng , Dai Chao , Qimin Song , Lei Han , Hongyan Li , Yucheng Lu , Mingguang Wang

Endocytosis plays a pivotal role in shaping the immunosuppressive landscape of gliomas, yet its spatial dynamics within the tumor microenvironment remain incompletely understood. Here, we integrated single-cell and spatial transcriptomic analyses to characterize endocytosis-related regulators involved in immune remodeling. Among them, FCGR2B, CLEC7A, and LYAR emerged as key modulators associated with the spatiotemporal heterogeneity of tumor-associated macrophages (TAMs) and malignant cells. These genes displayed regionally elevated transcript levels from the tumor–normal interface toward perivascular and necrotic regions, accompanied by progressively stronger spatial co-localization with M2-like macrophages across multiple spatial scales. Cell–cell communication analysis revealed that these regulators were linked to activation of endocytosis-associated signaling pathways, including SPP1, GRN, and PSAP. A prognostic risk score derived from their expression effectively stratified patients by molecular subtype and clinical outcome, and SHAP-based model interpretation quantified the contribution of each gene to risk prediction. Immunohistochemistry and Western blot analyses further validated their elevated protein expression in high-grade glioma tissues. Collectively, this spatial multi-omic framework delineates endocytosis-associated immune remodeling in glioma and identifies FCGR2B, CLEC7A, and LYAR as potential biomarkers and therapeutic targets for disrupting immunosuppressive niches.

内吞作用在形成神经胶质瘤的免疫抑制景观中起着关键作用，但其在肿瘤微环境中的空间动力学仍然不完全清楚。在这里，我们整合了单细胞和空间转录组学分析来表征参与免疫重塑的内吞相关调节因子。其中，FCGR2B、CLEC7A和LYAR是与肿瘤相关巨噬细胞（tumor-associated macrophages, tam）和恶性细胞时空异质性相关的关键调节因子。这些基因表现出从肿瘤-正常界面到血管周围和坏死区域的区域性转录水平升高，并伴随着与m2样巨噬细胞在多个空间尺度上逐渐增强的空间共定位。细胞间通讯分析显示，这些调节因子与胞吞相关信号通路的激活有关，包括SPP1、GRN和PSAP。根据其表达得出的预后风险评分有效地根据分子亚型和临床结果对患者进行分层，基于shap的模型解释量化了每个基因对风险预测的贡献。免疫组织化学和Western blot分析进一步证实了它们在高级别胶质瘤组织中的蛋白表达升高。总的来说，这个空间多组学框架描绘了胶质瘤中与内吞相关的免疫重塑，并确定了FCGR2B、cle7a和LYAR作为破坏免疫抑制生态位的潜在生物标志物和治疗靶点。

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引用次数: 0

MICU1 promotes Ca2+ homeostasis and curbs ferroptosis to attenuate brain tissue damage in rats with postoperative cognitive dysfunction MICU1促进Ca2+稳态和抑制铁下垂，以减轻术后认知功能障碍大鼠的脑组织损伤。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-03 DOI: 10.1016/j.brainres.2025.150087

Na Zhou , Yan Wang

Objective

Postoperative cognitive dysfunction (POCD) is severe in patients after anesthesia and surgery. This study investigates the mechanism by which MICU1 regulates Ca²⁺ homeostasis and ferroptosis in POCD rats.

Methods

A POCD rat model was established, and hippocampal tissue was collected from the CA1 region to assess MICU1 expression. The lentivirus carrying Ad-MICU1 or the ferroptosis inducer Erastin was injected into the right lateral ventricle of POCD rats, followed by evaluation of motor function, learning ability, and memory capacity. Inflammatory cytokines were measured using ELISA. Nissl staining, NeuN staining, and HE staining were conducted to observe morphological changes in neurons, surviving neurons in the hippocampal CA1 subregion, and neuronal localization. ELISA was performed to assay the levels of ATP, Ca²⁺, Fe²⁺, MDA, SOD, LPO, and GSH in rat hippocampal tissue in the CA1 region. Flow cytometry was conducted to measure total ROS levels, mitochondrial ROS levels, and mitochondrial MPP. The Seahorse XFe 96 analyzer was employed to measure the mitochondrial oxygen consumption rate. Western blot was conducted to examine the levels of ferroptosis-related proteins.

Results

MICU1 was reduced in POCD rats. MICU1 overexpression partially improved motor function, learning ability, and memory capacity and alleviated central inflammation and hippocampal neuronal damage in POCD rats. MICU1 maintained Ca²⁺ homeostasis, reduced Ca²⁺, total ROS, and mitochondrial ROS levels, and inhibited ferroptosis. Erastin partially reversed the beneficial effects of MICU1 overexpression on POCD rats.

Conclusion

MICU1 promotes Ca²⁺ homeostasis, inhibits ferroptosis and ROS production, and alleviates brain tissue damage in POCD rats.

目的：术后认知功能障碍（POCD）在麻醉术后患者中较为严重。本研究探讨MICU1调控POCD大鼠Ca2+稳态和铁下垂的机制。方法：建立POCD大鼠模型，取CA1区海马组织检测MICU1表达。将携带Ad-MICU1或铁下垂诱导剂Erastin的慢病毒注入POCD大鼠右侧脑室，评估其运动功能、学习能力和记忆能力。采用ELISA法检测炎症因子。采用Nissl染色、NeuN染色、HE染色观察神经元形态学变化、海马CA1亚区存活神经元及神经元定位。ELISA法检测CA1区大鼠海马组织中ATP、Ca2+、Fe2+、MDA、SOD、LPO、GSH水平。流式细胞术检测总ROS水平、线粒体ROS水平和线粒体MPP。采用Seahorse XFe 96分析仪测定线粒体耗氧量。Western blot检测凋亡相关蛋白水平。结果：POCD大鼠MICU1降低。MICU1过表达可部分改善POCD大鼠的运动功能、学习能力和记忆能力，减轻中枢炎症和海马神经元损伤。MICU1维持Ca2+稳态，降低Ca2+、总ROS和线粒体ROS水平，并抑制铁下垂。Erastin部分逆转了MICU1过表达对POCD大鼠的有益作用。结论：MICU1促进Ca2+稳态，抑制铁下垂和ROS的产生，减轻POCD大鼠脑组织损伤。

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引用次数: 0

Yank-related changes in corticospinal recruitment gain in humans 人类皮质脊髓招募增益的张力相关变化。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-03 DOI: 10.1016/j.brainres.2025.150090

Abdulkerim Darendeli , Mathew Yarossi , Spencer Lake Jakobs-Skolik , Nathaniel Pinkes , Vaishnavi Sharma , Erica Kemmerling , Eugene Tunik , Oscar Soto

The generation of muscle force is a key component of movement. Force is generated by increasing the number and firing rates of motor units (MU), but limited information is available on the corticospinal (CS) recruitment gain across the spectrum of magnitude and rate of force (yank). To assess the effects of force magnitude and yank on motor outputs, we recorded force (motor evoked twitches, METs) and EMG (motor evoked potentials, MEPs) in response to transcranial magnetic stimulation (TMS) during nearly isometric hand gripping tasks in 20 healthy subjects. Motor cortex TMS was applied during force ramps at different levels of voluntary force magnitude and yank. Yank robustly facilitated METs, maximally at lowest magnitudes of voluntary force, but this facilitation saturated at forces > 50 % of the maximal voluntary contraction (MVC). At each level of force magnitude there was a linear relationship between the yank of voluntary force and MET amplitude. The slope of this relationship, representing the CS recruitment gain, decayed exponentially with increasing magnitude of force. Changes in CS recruitment gain associated with force magnitude and yank were better explained by METs than by MEPs. A positive yank resulted in larger estimated maximal MET at 0 % force compared to static contractions. These results suggest that METs capture a robust yank-related increase in CS recruitment gain, which is blunted by limited MU availability at high force magnitude. We showed that the estimation of maximal motor outputs is optimally achieved in tasks in which force production is achieved with high yank.

肌肉力量的产生是运动的关键组成部分。力是通过增加运动单元（MU）的数量和发射速率产生的，但是关于皮质脊髓（CS）在力的大小和速率（猛拉）范围内的招募增益的信息有限。为了评估力的大小和拉力对运动输出的影响，我们记录了20名健康受试者在近等距手握任务中经颅磁刺激（TMS）反应的力（运动诱发抽搐，METs）和肌电图（运动诱发电位，MEPs）。运动皮质经颅磁刺激在不同的自主力大小和张力水平的力斜坡中应用。猛拉有力地促进METs，最大限度地在最小的自主力，但这种促进饱和力 > 50 %的最大自主收缩（MVC）。在每个水平的力的大小有一个线性关系的自愿力的猛拉和MET振幅。这个关系的斜率，表示CS的吸收增益，随着力的增加呈指数衰减。与力大小和拉力相关的CS招募增益的变化用METs比MEPs更好地解释。与静态收缩相比，在0 %的力下，积极的拉伸导致更大的估计最大MET。这些结果表明，METs捕获了与猛拉相关的CS招募增益的强劲增长，这在高强度下被有限的MU可用性所钝化。我们表明，最大运动输出的估计是最理想的实现在任务中，力的生产是实现与高张力。

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引用次数: 0

Examining functional connectivity in metabolic syndrome and small vessel disease: A novel approach to understanding olfactory dysfunction and Alzheimer’s disease 检查代谢综合征和小血管疾病的功能连接：一种理解嗅觉功能障碍和阿尔茨海默病的新方法。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-12-01 DOI: 10.1016/j.brainres.2025.150084

Hector Reyes , Jaime Mondragon , Conner Frank , Claire Murphy

Introduction

The prevalence of Alzheimer’s Disease (AD) is projected to triple by 2050, highlighting the need to identify early markers and underlying mechanisms associated with its progression. Olfactory dysfunction has emerged as an early indicator of AD, with its neural basis linked to changes in the medial temporal lobe and associated networks. Cardiovascular risk factors, including metabolic syndrome (MetS) and cerebral small vessel disease (SVD), have been implicated in neurodegenerative processes, yet their impact on olfactory network connectivity remains underexplored. This study aimed to investigate task-based functional connectivity in the olfactory network, medial temporal lobe, and default mode network among cognitively unimpaired individuals with MetS or SVD.

Method

Participants were grouped based on MetS and SVD status. Using fMRI, functional connectivity patterns during olfactory processing were analyzed for group differences.

Results

Functional connectivity revealed hypoconnectivity between the right angular gyrus and secondary olfactory cortex between MetS groups and altered connectivity between the hippocampus and frontoparietal control network between SVD groups. Both conditions demonstrated increased within-network cerebellar connectivity compared to controls.

Discussion

These findings highlight distinct neural alterations in olfactory and cognitive control networks associated with cardiovascular risk factors, providing novel insights into early brain changes linked to cardiovascular risk factors for dementia.

到2050年，阿尔茨海默病（AD）的患病率预计将增加两倍，这突出了识别与其进展相关的早期标志物和潜在机制的必要性。嗅觉功能障碍已成为阿尔茨海默病的早期指标，其神经基础与内侧颞叶和相关网络的变化有关。心血管危险因素，包括代谢综合征（MetS）和脑血管疾病（SVD），与神经退行性过程有关，但它们对嗅觉网络连通性的影响仍未得到充分探讨。本研究旨在探讨认知功能未受损的met或SVD患者嗅觉网络、内侧颞叶和默认模式网络中基于任务的功能连通性。方法：根据MetS和SVD状态对参与者进行分组。利用功能磁共振成像（fMRI）分析嗅觉处理过程中的功能连接模式。结果：功能连通性显示MetS组右角回与次级嗅觉皮层之间的连通性降低，SVD组海马与额顶叶控制网络之间的连通性改变。与对照组相比，这两种情况下的小脑网络内连通性都有所增加。讨论：这些发现强调了与心血管危险因素相关的嗅觉和认知控制网络的独特神经改变，为痴呆症心血管危险因素相关的早期大脑变化提供了新的见解。

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引用次数: 0

Cross-Disease myeloid remodeling along the GMP–TAM axis predicts immunotherapy response in glioma 沿GMP-TAM轴的跨疾病骨髓重塑预测胶质瘤的免疫治疗反应。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-30 DOI: 10.1016/j.brainres.2025.150083

Yuanyuan Zhang , Xin Liu , Shi Hua

Backgrounds

Immune checkpoint inhibitor-induced colitis (CICs) represents a state of systemic immune activation and is paradoxically associated with superior anti-tumor responses. This study has been designed to explore gene signatures derived from CICs that could identify the key immunological drivers, and predict sensitivity of immunotherapy in immunologically cold tumors e.g. glioma. Methods: We integrated bulk, single-cell, and spatial transcriptomic data from CICs and glioma cohorts. Cross-disease analysis have been performed to identify an immunotherapy-responsive granulocyte-monocyte progenitor (IR-GMP) signature. Risk score (RS) model has been constructed through LASSO regression, and have been validated for its potential prognostic as well as predictive values. Results: We have identified 112 IR-GMP genes enriched in pathways that may cause myeloid immunosuppression. A four-gene RS model (RAC2, LAPTM5, HCLS1, CD74) has been developed, and glioma patients have been divided into high- and low-risk groups based on the model. RS is an independent prognostic factor, and demonstrated to exhibit superior accuracy for predicting survival when combining with clinical variables. High-RS tumors exhibited immunosuppressive TME characterized by M2 macrophage enrichment, SPP1-signaling hyperactivation, and an immune-tolerant genomic landscape (C4 subtype). Crucially, the high-RS group showed significantly higher immunophenoscores under PD-1 and combined PD-1/CTLA-4 blockade, indicating potential sensitivity to immunotherapy, and distinct chemotherapy susceptibility. Single-cell and spatial transcriptomic results confirmed the lineage specificity and regional colocalization of RS genes with M2 macrophages. Conclusions: Our cross-disease analysis unveils a conserved GMP–TAM myeloid remodeling axis in glioma. The derived RS model may serve as a powerful marker for predicting prognosis, and also for predicting the benefits derived from immunotherapy, offering a novel tool for precision immunotherapy in glioma.

背景：免疫检查点抑制剂诱导的结肠炎（CICs）代表了一种全身性免疫激活状态，并且矛盾地与优越的抗肿瘤反应相关。本研究旨在探索来自CICs的基因特征，这些特征可以识别关键的免疫驱动因素，并预测免疫治疗对免疫冷肿瘤（如胶质瘤）的敏感性。方法：我们整合了来自CICs和胶质瘤队列的大量、单细胞和空间转录组数据。已经进行了跨疾病分析，以确定免疫治疗反应性粒细胞-单核细胞祖细胞（IR-GMP）特征。通过LASSO回归构建了风险评分（RS）模型，并对其潜在的预后和预测价值进行了验证。结果：我们已经鉴定出112个富集于髓细胞免疫抑制通路的IR-GMP基因。建立了四基因RS模型（RAC2、LAPTM5、HCLS1、CD74），并根据模型将胶质瘤患者分为高危组和低危组。RS是一个独立的预后因素，当与临床变量相结合时，RS在预测生存方面表现出更高的准确性。高rs肿瘤表现出免疫抑制TME，其特征是M2巨噬细胞富集、spp1信号过度激活和免疫耐受基因组景观（C4亚型）。至关重要的是，高rs组在PD-1和PD-1/CTLA-4联合阻断下显示出显著更高的免疫表型，表明对免疫治疗的潜在敏感性和明显的化疗敏感性。单细胞和空间转录组学结果证实了RS基因与M2巨噬细胞的谱系特异性和区域共定位。结论：我们的跨疾病分析揭示了胶质瘤中保守的GMP-TAM髓系重塑轴。所建立的RS模型可作为预测预后的有力指标，也可用于预测免疫治疗的获益，为胶质瘤的精确免疫治疗提供了新的工具。

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引用次数: 0

Static and dynamic alterations in local brain activity and their association with dysfunctional connectivity in depressed adolescents with suicide attempts and non-suicidal self-injury 有自杀企图和非自杀性自伤的抑郁青少年局部脑活动的静态和动态变化及其与功能障碍连接的关系

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-11-29 DOI: 10.1016/j.brainres.2025.150064

Lianlian Yang , Shuai Wang , Zimo Zhou , Zhenru Guo , Shuaiyi Guo , Xiaoshan Gao , Yuanyuan Yang , Yu Xia , Haixia Huang , Jianhua Li , Haohao Zhu , Lin Tian

Suicide attempts (SA) and non-suicidal self-injury (NSSI) are critical public health concerns that frequently co-occur in depressed adolescents. However, the neurological mechanisms underlying these behaviors remain poorly understood. This study aimed to identify alterations in brain activity and examine the associations between these changes and clinical symptom severity in depressed adolescents with SA and NSSI. A total of 82 depressed adolescents with NSSI were divided into two groups: those with both SA and NSSI (SA + NSSI, n = 46) and those with NSSI only (n = 36). Static amplitude of low-frequency fluctuation (sALFF) and dynamic ALFF variability (dALFF variability) analyses were conducted to assess local brain activity differences between groups. Regions with abnormal neural activity were used as seeds to investigate static functional connectivity (sFC) and dynamic FC variability (dFC variability) alterations. Correlation analyses as exploratory analysis was subsequently performed. Compared to the NSSI group, the SA + NSSI group exhibited increased sALFF in the left cerebellum, increased dALFF variability in the orbitofrontal cortex and left cerebellum, and increased dFC variability between the orbitofrontal cortex and caudate. The SA + NSSI group also showed decreased sALFF and dALFF variability in the postcentral gyrus (cluster p < 0.05, FDR corrected, two-tailed). Additionally, for the SA + NSSI group, sALFF in the postcentral gyrus was negatively correlated with emotional neglect, while the dFC variability between the orbitofrontal cortex and caudate was positively correlated with internet addiction withdrawal symptoms. These findings provide novel insights into the neurological mechanisms of SA and NSSI, highlighting the potential value of combining static and dynamic functional metrics for clinical differentiation between these behaviors.

自杀企图（SA）和非自杀性自伤（NSSI）是严重的公共卫生问题，经常在抑郁青少年中同时发生。然而，这些行为背后的神经机制仍然知之甚少。本研究旨在确定青少年抑郁伴SA和自伤的大脑活动的变化，并研究这些变化与临床症状严重程度之间的关系。将82例有自伤的抑郁青少年分为两组：有自伤和有自伤的抑郁青少年（SA + 自伤，n = 46）和有自伤的抑郁青少年（n = 36）。通过静态低频波动幅度（sALFF）和动态低频波动幅度（dALFF变异性）分析来评估组间局部脑活动的差异。以神经活动异常区域为种子，研究静态功能连通性（sFC）和动态FC变异性（dFC变异性）的变化。随后进行相关性分析作为探索性分析。与自伤组相比，SA + 自伤组左侧小脑的sALFF增加，眶额皮质和左侧小脑的dALFF变异性增加，眶额皮质和尾状核之间的dFC变异性增加。SA + 自伤组也显示中枢后回sALFF和dALFF变异性降低(簇p

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引用次数: 0