Brain Research最新文献_第9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 : 2026-02-01 Epub 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

Strength of associations between regional brain volumes and dual decline in gait and memory 区域脑容量与步态和记忆双重衰退之间的关联强度。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-02-01 Epub Date: 2025-11-28 DOI: 10.1016/j.brainres.2025.150072

Sadhani Karunarathna , Monique Breslin , Jane Alty , James Scott McDonald , Richard Beare , Velandai K. Srikanth , Taya A. Collyer , Michele L. Callisaya

Background

Dual decline in gait and memory is associated with a higher risk of dementia. However, little is known about specific brain regions and their association with dual decline. Therefore, this study examined the strength of associations between baseline regional brain volumes and dual decline in gait speed and memory.

Methods

Participants aged over 60 years were randomly selected from the Southern Tasmanian electoral roll. Participants (n = 266) were classified into four groups depending on tertiles of annual decline in gait speed and delayed memory recall: non-decline, gait-only decline, cognitive-only decline, and dual decline. Multinomial logistic regression was used to examine the strength of associations between baseline regional brain volumes and the four groups.

Results

The mean age of participants was 70.9 ± SD 6.7 years. For the dual decline group, eight regions (in order of strength − orbitofrontal cortex, middle frontal gyrus, superior frontal gyrus, thalamus, anterior cingulate cortex, brainstem, inferior temporal gyrus and hippocampus) had relative risk ratios below 0.60 for a 1 SD increase in volume. For gait-only and cognitive-only decline, only the thalamus and cerebellum respectively, had relative risk ratios below 0.60.

Conclusions

In this study, we observed that smaller volumes in regions related to memory, executive function, motor, and sensory-motor integration had the strongest associations with dual decline.

背景：步态和记忆的双重衰退与痴呆的高风险相关。然而，人们对特定的大脑区域及其与双重衰退的关系知之甚少。因此，本研究考察了基线区域脑容量与步态速度和记忆力双重衰退之间的关联强度。方法：从南塔斯马尼亚州选民名册中随机选择年龄在60岁 以上的参与者。参与者（n = 266）根据步态速度和延迟记忆回忆的年度下降的分位数分为四组：非下降，仅步态下降，仅认知下降和双重下降。使用多项逻辑回归来检查基线区域脑容量与四组之间的关联强度。结果：参与者的平均年龄为70.9 ± SD 6.7 岁。对于双衰退组，体积每增加1 SD， 8个区域（按强度排序为眶额皮质、额中回、额上回、丘脑、前扣带皮层、脑干、颞下回和海马）的相对风险比低于0.60。对于单纯步态衰退和单纯认知衰退，分别只有丘脑和小脑的相对风险比低于0.60。结论：在这项研究中，我们观察到，与记忆、执行功能、运动和感觉-运动整合相关的区域体积较小，与双重衰退有最强的关联。

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引用次数: 0

Oxidative Stress-Induced mechanisms in neurodegeneration and Eryptosis: Implications for neurological and systemic disorders 氧化应激诱导的神经退行性变和下垂机制：对神经和全身疾病的影响。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-02-01 Epub Date: 2025-12-11 DOI: 10.1016/j.brainres.2025.150111

Marijana Markovic Boras , Vanja Krulj , Alma Karahmet , Kanita Omerbasic , Asma Nawaz , Doris Pavković , Emina K. Sher

The significant association between development of neurological diseases, like Alzheimer’s, Parkinson’s or depression and oxidative stress occurs from disturbance in the balance between oxidative and antioxidative processes due to chronic stress. Unlike previous reviews that focused only on neurological or systemic diseases, this review discusses the mechanisms that connect oxidative stress and neuroinflammation or eryptosis in both neurological, neurodegenerative, and various systemic diseases, clarifying two completely distinct mechanisms of response to oxidative stress that are common to multiple clinical conditions. This review explores the complex involvement of oxidative damage in neurodegeneration and explains its contribution to inflammation, protein aggregation, and disruption of cellular functions. Crucial components in this process are reactive oxygen and reactive nitrogen species, which can be generated both endogenously or exogenously. Primary sources of ROS in cells are NADPH oxidases, mitochondria, xanthine oxidase and growth factor receptors. Elevated ROS levels disrupt cellular homeostasis and cause oxidative damage and inflammatory responses in neurological disorders characterised by the activation of microglia, astrocytes, and infiltrating CD4 + T cells. Similarly, in systemic disease, this disruption happens through eryptosis. In addition, chronic stress damages antioxidant defence, which further worsens pathological processes. A deeper understanding of the underlying mechanisms provides novel insights into therapeutic strategies for reducing the effects of oxidative stress in both neurological and systemic diseases.

神经系统疾病，如阿尔茨海默氏症、帕金森氏症或抑郁症的发展与氧化应激之间的重要联系，是由于慢性应激导致氧化和抗氧化过程之间的平衡受到干扰。与以往仅关注神经系统或全身性疾病的综述不同，本综述讨论了神经系统、神经退行性和各种全身性疾病中氧化应激与神经炎症或神经萎蔫之间的联系机制，阐明了多种临床疾病中常见的两种完全不同的氧化应激反应机制。这篇综述探讨了神经变性中氧化损伤的复杂参与，并解释了其对炎症、蛋白质聚集和细胞功能破坏的贡献。这一过程的关键成分是活性氧和活性氮，它们可以由内源或外源产生。细胞中ROS的主要来源是NADPH氧化酶、线粒体、黄嘌呤氧化酶和生长因子受体。在以小胶质细胞、星形胶质细胞激活和CD4 + T细胞浸润为特征的神经系统疾病中，ROS水平升高会破坏细胞稳态，引起氧化损伤和炎症反应。类似地，在全身性疾病中，这种破坏通过后倾发生。此外，慢性应激损害抗氧化防御，从而进一步恶化病理过程。对潜在机制的深入了解为减少神经系统和全身性疾病中氧化应激的影响提供了新的治疗策略。

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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 : 2026-02-01 Epub 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

Sex differences in interactions between the muscarinic-1 and orexin-1 receptors on cognitive flexibility in rats 肌肉素-1和食欲素-1受体对大鼠认知灵活性相互作用的性别差异。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-02-01 Epub Date: 2025-11-27 DOI: 10.1016/j.brainres.2025.150081

Mutian Li , Jim R. Fadel , Joshua A. Burk

Previous research has shown that cognitive flexibility, the ability to adjust to different rules, is affected by manipulations of orexin and acetylcholine (ACh). Because there are strong neural connections between orexin and ACh, these two neurotransmitter systems may interact to impact cognitive flexibility. In the present experiment, the effects of pharmacological manipulations of orexin-1 and muscarinic-1 receptors in rats were tested on cognitive flexibility. Rats received intraperitoneal injections of VU0453595, a positive allosteric modulator for the M1 subtype of ACh receptors, for seven days prior to a rule switch in a measure of cognitive flexibility. On the day of the rule switch, rats were given the orexin-1 receptor antagonist, SB-334867 or vehicle prior to task performance. As expected, SB-334867 increased the number of trials to criterion during the rule switch. Compared to vehicle, when VU0453595 was administered, orexin-1 receptor blockade increased regressive errors for males and perseverative errors for females. These findings support the hypothesis that there are interactions between the orexin and cholinergic systems affecting cognitive flexibility, but that these interactions affect cognitive flexibility differently for males and females.

先前的研究表明，认知灵活性，即适应不同规则的能力，受到食欲素和乙酰胆碱（ACh）的影响。因为食欲素和乙酰胆碱之间有很强的神经联系，这两种神经递质系统可能相互作用，影响认知灵活性。本实验研究了食欲素-1和肌碱-1受体的药理作用对大鼠认知灵活性的影响。在认知灵活性测量的规则转换之前，大鼠接受了VU0453595腹腔注射，VU0453595是一种阳性的乙酰胆碱受体M1亚型的变构调节剂。在规则转换当天，大鼠在执行任务前给予食欲素-1受体拮抗剂SB-334867或对照品。正如预期的那样，SB-334867在规则切换期间增加了到标准的试验次数。与对照组相比，当给药VU0453595时，食欲素-1受体阻断增加了雄性的回归误差和雌性的持久性误差。这些发现支持了一种假设，即食欲素和胆碱能系统之间存在影响认知灵活性的相互作用，但这些相互作用对男性和女性认知灵活性的影响不同。

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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 : 2026-02-01 Epub 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

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 : 2026-02-01 Epub 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

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 : 2026-02-01 Epub 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

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 : 2026-02-01 Epub 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

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 : 2026-02-01 Epub 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