Neuroscience最新文献_第8页

Anatomical and neurochemical profiles of somatostatin-positive neurons in the mouse inferior colliculus. 小鼠下丘生长抑素阳性神经元的解剖和神经化学特征。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-06 DOI: 10.1016/j.neuroscience.2026.03.004

Ryohei Tomioka, Kenta Kobayashi, Wen-Jie Song

The inferior colliculus (IC) integrates auditory information through a complex interplay of excitatory and inhibitory neurons, and provides both excitatory and inhibitory inputs to the medial geniculate body (MGB). Although IC projection neurons are predominantly glutamatergic, accumulating evidence suggests that they comprised heterogeneous subpopulations with distinct morphological and functional properties. Somatostatin (SST)-expressing neurons represent one such glutamatergic subpopulation; however, their characteristics and circuit organization remain poorly understood. In this study, we examined the projection domains within the MGB and the local circuits of SST-expressing neurons in the IC. SST-expressing neurons in the central nucleus of the IC (CNIC) project mainly to the ventral division of the MGB (MGv) and posterior limiting nucleus (POL), whereas those in the external (ECIC) and dorsal (DCIC) nuclei primarily target the POL. The SST axon terminals in the MGv were large, formed clusters, and positive for cholecystokinin (CCK), whereas those projecting to the POL were small, non-clustered, and CCK-negative. The local axons of SST-positive neurons in the IC formed vesicular glutamate transporter 2-positive basket-like terminals around large γ-amino butyric acid (GABA)-ergic neurons, a hallmark morphological profile of GABAergic projection neurons to the MGB. This finding indicates that SST-expressing neurons provide strong excitatory input to these inhibitory projection neurons. Collectively, our results show that IC SST-expressing neurons shape thalamic processing not only through direct excitatory inputs to the MGv and POL, but also indirectly via strong excitation of local GABAergic projection neurons, thereby positioning SST neurons as key regulators of IC-MGB communication.

下丘（IC）通过兴奋性和抑制性神经元的复杂相互作用整合听觉信息，并向内侧膝状体（MGB）提供兴奋性和抑制性输入。虽然IC投射神经元主要是谷氨酸能神经元，但越来越多的证据表明它们由具有不同形态和功能特性的异质亚群组成。表达生长抑素（SST）的神经元代表了这样一个谷氨酸能亚群；然而，它们的特性和电路组织仍然知之甚少。在这项研究中，我们研究了MGB内的投射域和IC中表达sst神经元的局部电路。IC中央核（CNIC）的sst表达神经元主要投射到MGB的腹侧分裂（MGv）和后限制核（POL），而外核（ECIC）和背核（DCIC）的sst表达神经元主要靶向POL。MGv的SST轴突末端较大，形成簇状，CCK阳性，而那些投射到POL的轴突末端较小，非簇状，CCK阴性。IC中sst阳性神经元的局部轴突在大γ-氨基丁酸（GABA）能神经元周围形成囊状谷氨酸转运蛋白2阳性篮状末端，这是GABA能投射神经元到MGB的标志性形态学特征。这一发现表明，表达sst的神经元为这些抑制性投射神经元提供了强烈的兴奋性输入。综上所述，我们的研究结果表明，表达IC SST的神经元不仅通过对MGv和POL的直接兴奋性输入，还通过对局部gaba能投射神经元的强烈激发间接影响丘脑加工，从而将SST神经元定位为IC- mgb通信的关键调节器。

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引用次数: 0

NINJ1 monoclonal antibody alleviates neuroinflammation and promotes functional recovery after spinal cord injury by suppressing pyroptosis-mediated DAMPs release. NINJ1单克隆抗体通过抑制焦热介导的DAMPs释放，减轻脊髓损伤后的神经炎症，促进功能恢复。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-06 DOI: 10.1016/j.neuroscience.2026.03.002

Siyuan Yao, Wancheng Lin, Yao Zhang, Meng Yi, Shijie Liu, Jipeng Song, Yukun Yin, Ding Lixiang

Background: Secondary spinal cord injury (SCI) involves intense neuroinflammation driven by pyroptosis and damage-associated molecular patterns (DAMPs). Targeting NINJ1, an executioner protein for plasma membrane rupture, may break this cycle.

Methods: A mouse contusion SCI model was used, with groups including Sham, Vehicle, Methylprednisolone, and low/high-dose NINJ1 monoclonal antibody (mAb). Functional recovery was assessed by BMS scoring and gait analysis. Histopathology and molecular changes (neuronal survival, pyroptosis proteins GSDMD/NLRP3/Caspase-1, microglial polarization markers, and related pathways) were analyzed at 14 dpi. HMGB1 release was quantified. An in vitro co-culture model of glutamate-injured HT22 neurons and BV2 microglia validated the effects.

Results: NINJ1 mAb treatment significantly improved motor function and reduced pathology versus controls. It enhanced neuronal survival, suppressed pyroptosis executers (GSDMD, while NINJ1 mRNA expression remained unchanged), and decreased HMGB1 release. The treatment shifted microglial polarization from pro-inflammatory M1 to anti-inflammatory M2, correlating with reduced nuclear p-NF-κB p65 and increased p-STAT3. In vitro, NINJ1 mAb directly protected neurons and suppressed microglial M1 polarization and pro-inflammatory cytokine release.

Conclusion: The NINJ1 monoclonal antibody promotes recovery after SCI by inhibiting pyroptotic membrane rupture, reducing DAMP release, and modulating microglia toward an anti-inflammatory phenotype, presenting a novel therapeutic strategy.

背景：继发性脊髓损伤（SCI）涉及由焦亡和损伤相关分子模式（DAMPs）驱动的强烈神经炎症。靶向质膜破裂的刽子手蛋白NINJ1可能会打破这一循环。方法：采用小鼠挫伤性脊髓损伤模型，分为Sham组、Vehicle组、甲基强的松龙组和低/高剂量NINJ1单克隆抗体（mAb）组。通过BMS评分和步态分析评估功能恢复情况。在14 dpi时分析组织病理学和分子变化（神经元存活、焦亡蛋白GSDMD/NLRP3/Caspase-1、小胶质极化标记物及相关通路）。测定HMGB1的释放量。谷氨酸损伤HT22神经元与BV2小胶质细胞体外共培养模型验证了这种效果。结果：与对照组相比，NINJ1 mAb治疗显著改善了运动功能，减少了病理。增强神经元存活，抑制焦亡执行子（GSDMD，而NINJ1 mRNA表达不变），减少HMGB1释放。治疗将小胶质细胞极化从促炎M1转变为抗炎M2，与核p-NF-κB p65减少和p-STAT3增加相关。在体外，NINJ1 mAb直接保护神经元，抑制小胶质细胞M1极化和促炎细胞因子释放。结论：NINJ1单克隆抗体通过抑制热噬膜破裂，减少DAMP释放，调节小胶质细胞向抗炎表型的方向发展，促进脊髓损伤后的恢复，是一种新的治疗策略。

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引用次数: 0

Gray-white matter contrast as an index of neurobiological alterations in anorexia nervosa 灰质对比作为神经性厌食症神经生物学改变的指标。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-05 Epub Date: 2026-01-14 DOI: 10.1016/j.neuroscience.2026.01.012

Sanberk Ugur , Christopher R. Madan , Valentina Meregalli , Sofia Gentili , Serena Giovannini , Marco Romanelli , Renzo Manara , Angela Favaro , Enrico Collantoni

This neuroimaging study sought to characterize differences in cortical gray-white matter contrast (GWC) between individuals with anorexia nervosa (AN) and age-matched healthy controls (HC) and compare these findings with conventional cortical thickness (CT) measures. The study included 58 female participants (29 AN, 29 HC). T1-weighted images were acquired using a 3 T scanner and processed with FreeSurfer. GWC maps were calculated at each cortical vertex. Vertex-wise general linear models assessed group differences in GWC controlling for age only, and controlling for age and vertex-wise CT. A separate model tested CT differences. Models were corrected for multiple comparisons using cluster-wise correction. Spearman correlations related mean GWC in significant clusters to BMI at scan, age at onset, and illness duration. The age-only model revealed two clusters in the left hemisphere with higher GWC in patients with AN, namely the inferior temporal cortex and medial orbitofrontal cortex. No clusters survived in the model controlling for age and CT. The CT analysis revealed no significant group differences. Mean GWC in clusters did not correlate with clinical severity indices in AN. Patients with AN exhibit focal increases in GWC despite the absence of detectable cortical thinning, suggesting that the GWC can provide complementary information in understanding the neurobiology of AN. The elimination of GWC differences when adjusting for CT likely reflects shared variance rather than true absence of effect. Lack of correlations with clinical indices may be due to limited sample size. Future longitudinal and multimodal studies are warranted to determine the underpinnings of GWC alterations.

本神经影像学研究旨在描述神经性厌食症（AN）患者和年龄匹配的健康对照（HC）之间皮层灰质对比（GWC）的差异，并将这些结果与常规皮层厚度（CT）测量结果进行比较。该研究包括58名女性参与者（29名男性，29名男性）。使用3 T扫描仪获取t1加权图像，并使用FreeSurfer进行处理。在每个皮质顶点处计算GWC图。顶点方向的一般线性模型评估了仅控制年龄的GWC和控制年龄和顶点方向CT的组间差异。一个单独的模型测试CT差异。使用聚类校正对模型进行多次比较校正。Spearman相关性与扫描时BMI、发病年龄和病程相关。仅年龄模型显示，AN患者的左半球有两个GWC较高的簇，即下颞叶皮质和内侧眶额皮质。在控制年龄和CT的模型中，没有集群存活。CT分析显示各组间无明显差异。群集的平均GWC与AN的临床严重程度指数无关。尽管没有可检测到的皮质变薄，但AN患者的GWC表现出局灶性增加，这表明GWC可以为理解AN的神经生物学提供补充信息。当调整CT时，GWC差异的消除可能反映了共同的方差，而不是真正的没有影响。与临床指标缺乏相关性可能是由于样本量有限。未来的纵向和多模态研究有必要确定GWC变化的基础。

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引用次数: 0

A multi-target therapeutic framework for Alzheimer’s disease: an integrative mechanistic review 阿尔茨海默病的多靶点治疗框架：综合机制综述。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-05 Epub Date: 2026-01-09 DOI: 10.1016/j.neuroscience.2026.01.010

Ousman Bajinka , Lamarana Jallow , Guven Ozdemir

Background: Alzheimer’s disease (AD) is increasingly recognized as a multifactorial network disorder in which amyloid and tau pathology interact with mitochondrial dysfunction, neuroinflammation, metabolic impairment, vascular dysregulation, and synaptic failure. This review provides an integrative, systems-level synthesis of these mechanisms with emphasis on diagnostic and therapeutic implications. Methods: A structured narrative review was conducted using PubMed, Scopus, Web of Science, and Embase (2010–2025). Eligible studies included clinical trials, biomarker validation studies, cohort analyses, and mechanistic investigations. Evidence was synthesized by mechanistic domain with focus on cross-system interactions and translational relevance. Findings: Convergent data indicate that soluble Aβ species, tau propagation, glial dysregulation, insulin resistance, mitochondrial bioenergetic failure, lipid imbalance, and BBB dysfunction form a self-reinforcing neurodegenerative network. Diagnostic advances—including plasma p-tau181/217, Aβ42/40 ratio, GFAP, sTREM2, neuronal exosomes, and multimodal machine-learning models—enable earlier staging and refinement of therapeutic selection. Therapeutic development is shifting from linear amyloid removal to multi-target strategies incorporating anti-tau agents, glial-modulating compounds, metabolic and microbiome interventions, medical nutrition, and multidomain lifestyle programs. Across trials, combined strategies targeting interacting mechanisms demonstrate stronger biomarker and cognitive effects than single-axis approaches. Conclusions: AD management requires a systems-oriented therapeutic architecture in which interventions are selected based on mechanistic dominance, biomarker stage, and potential synergy. We outline a multi-target strategy integrating amyloid/tau modulation, neuroimmune regulation, metabolic-vascular stabilization, and synaptic support. Future work should prioritize biomarker-guided stratification, treatment sequencing, and prevention-oriented combination designs.

背景：阿尔茨海默病（AD）越来越被认为是一种多因子网络疾病，其中淀粉样蛋白和tau蛋白病理与线粒体功能障碍、神经炎症、代谢损伤、血管失调和突触衰竭相互作用。这篇综述提供了一个综合的，系统水平的综合这些机制，重点是诊断和治疗的意义。方法：使用PubMed、Scopus、Web of Science和Embase（2010-2025）进行结构化的叙述性综述。符合条件的研究包括临床试验、生物标志物验证研究、队列分析和机制调查。证据是由机械领域合成的，重点是跨系统的相互作用和翻译相关性。研究结果：趋同的数据表明，可溶性a β物种、tau增殖、胶质细胞失调、胰岛素抵抗、线粒体生物能量衰竭、脂质失衡和血脑屏障功能障碍形成了一个自我强化的神经退行性网络。诊断方面的进步——包括血浆p-tau181/217、a - β42/40比值、GFAP、sTREM2、神经元外泌体和多模态机器学习模型——使治疗选择的早期分期和细化成为可能。治疗发展正在从线性淀粉样蛋白去除转向多靶点策略，包括抗tau药物、神经胶质调节化合物、代谢和微生物组干预、医学营养和多领域生活方式计划。在所有试验中，针对相互作用机制的联合策略比单轴方法显示出更强的生物标志物和认知效果。结论：AD管理需要一个以系统为导向的治疗体系，其中干预措施的选择基于机制优势、生物标志物分期和潜在的协同作用。我们概述了一种整合淀粉样蛋白/tau调节、神经免疫调节、代谢血管稳定和突触支持的多靶点策略。未来的工作应优先考虑生物标志物引导的分层、治疗测序和预防导向的组合设计。

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引用次数: 0

Effects of personalized vs. non-personalized neurostimulation protocols in improving speech and limb reaction times 个性化与非个性化神经刺激方案对改善言语和肢体反应时间的影响。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-05 Epub Date: 2026-01-11 DOI: 10.1016/j.neuroscience.2026.01.007

Fatemeh Tabari , Joel Isaac Berger , Arend W.A. Van Gemmert , Melda Kunduk , Karim Johari

Abnormal activity within supplementary motor area (SMA) has been associated with impaired speech and limb movement in neurological conditions. Normalizing aberrant neural activity through non-invasive neuromodulation techniques over SMA has demonstrated promising effects in ameliorating motor and non-motor functions. However, there is limited research on the application of transcranial electrical stimulation (tES) over the left SMA as a potential non-invasive protocol to improve speech production. In this study, we examined the effects of several tES protocols, including high-definition transcranial alternating current stimulation (HD-tACS), transcranial random noise stimulation (tRNS), and direct current stimulation (HD-tDCS), targeting the left SMA in neurotypical adults, on speech and limb reaction times. In a sham-controlled dual-experiment design, two groups of neurologically intact adult participants underwent multiple stimulation sessions: Experiment 1) sham HD-tACS, HD-tACS tuned to each individual’s frequency of maximal SMA beta activity (15–30 Hz) during speech (tuned-to-speech) or limb (tuned-to-limb), or HD-tRNS; Experiment 2) sham, anodal or cathodal HD-tDCS. Following the stimulation, the participants were instructed to perform a speech-limb interleaved task. Personalized beta HD-tACS and HD-tRNS – but not HD-tDCS – over the left SMA significantly improved reaction times for both speech and limb movement compared to sham. There was no difference in reaction times between HD-tACS and HD-tRNS for either speech or limb movement. These findings demonstrate comparable neuromodulatory effects of HD-tACS and HD-tRNS in improving speech and limb reaction times in younger adults. This study is exploratory and warrants replication with a larger sample within a single-group design.

在神经系统疾病中，辅助运动区（SMA）的异常活动与言语和肢体运动受损有关。通过非侵入性神经调节技术在SMA上正常化异常神经活动在改善运动和非运动功能方面显示出有希望的效果。然而，关于经颅电刺激（tES）在左侧SMA上的应用作为一种潜在的非侵入性方案来改善语音产生的研究有限。在这项研究中，我们研究了几种tES方案的影响，包括高分辨率经颅交流电刺激（HD-tACS），经颅随机噪声刺激（tRNS）和直流电刺激（HD-tDCS），针对神经典型成人的左侧SMA，对语言和肢体反应时间的影响。在假对照双实验设计中，两组神经功能完整的成年参与者接受了多次刺激：实验1)假HD-tACS， HD-tACS调节到每个人在说话（调节到说话）或肢体（调节到肢体）或HD-tRNS期间的最大SMA β活动频率（15-30 Hz）；实验2)假、阳极或阴极HD-tDCS。在刺激之后，参与者被要求执行一项言语肢体交织任务。与假手术相比，个性化的β HD-tACS和HD-tRNS（而不是HD-tDCS）在左侧SMA上显著改善了言语和肢体运动的反应时间。HD-tACS和HD-tRNS在言语和肢体运动方面的反应时间没有差异。这些发现表明，HD-tACS和HD-tRNS在改善年轻人的语言和肢体反应时间方面具有相当的神经调节作用。这项研究是探索性的，并保证在单组设计中使用更大的样本进行复制。

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引用次数: 0

Antibody drug conjugates in Alzheimer’s disease: emerging strategies and future directions 阿尔茨海默病的抗体药物偶联物：新策略和未来方向。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-05 Epub Date: 2025-12-20 DOI: 10.1016/j.neuroscience.2025.12.053

Mandana AmeliMojarad, Melika AmeliMojarad

Antibody–drug conjugates (ADCs) are emerging as a targeted therapeutic strategy for Alzheimer’s disease (AD), offering precise delivery of disease modifying agents with reduced systemic toxicity. By linking monoclonal antibodies to small-molecule payloads, ADCs hold promise in overcoming key challenges in AD treatment, including poor blood–brain barrier (BBB) penetration and off-target effects. This review provides a critical synthesis of ADC strategies in neurodegeneration, with emphasis on molecular design, payload selection, and delivery mechanisms. Distinctively, we integrate lessons from oncology-based ADC development into the neurodegenerative context, highlighting how these cross disciplinary insights open new avenues for tackling multifactorial AD pathology, including amyloid-beta (Aβ) and tau-related mechanisms. By outlining translational progress, ongoing clinical efforts, and future directions, this review positions ADCs not only as a promising precision medicine approach but also as a novel framework for advancing therapeutic innovation in complex neurodegenerative disorders.

抗体-药物偶联物（adc）正成为阿尔茨海默病（AD）的一种靶向治疗策略，它提供了具有降低全身毒性的疾病修饰剂的精确递送。通过将单克隆抗体连接到小分子有效载荷，adc有望克服AD治疗中的关键挑战，包括血脑屏障（BBB）穿透性差和脱靶效应。本文综述了神经退行性疾病中ADC策略的关键综合，重点是分子设计、有效载荷选择和递送机制。特别的是，我们将基于肿瘤学的ADC发展的经验教训整合到神经退行性背景下，强调这些跨学科的见解如何为解决多因子AD病理开辟新的途径，包括淀粉样蛋白- β (Aβ)和tau相关机制。通过概述转化进展、正在进行的临床努力和未来的方向，本综述将adc定位为一种有前途的精准医学方法，同时也是推进复杂神经退行性疾病治疗创新的新框架。

引用次数: 0

Temporal interference non-invasive deep brainstimulation: bibliometric, clinical translation and potential for neurorestoratology 时间干扰非侵入性脑深部刺激：文献计量学、临床翻译和神经修复学潜力。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-05 Epub Date: 2025-12-13 DOI: 10.1016/j.neuroscience.2025.12.031

Zhanxiang Lin , Weixian Zeng , Weili Zhu , Cheng Tan , Zicai Liu

Background and objectives

Temporal interference stimulation (TIS) is a novel, non-invasive neuromodulation technique that effectively overcomes the depth and electric field dispersion issues of conventional transcranial electrical stimulation. TIS holds promise for achieving greater functional recovery than current neural repair methods. This study aims to assess the current status, trends, and hotspots in TIS development, review its evolution, explore its advanced applications in neurorestoratology, and provide theoretical and practical guidance for its future advancement.

Materials and methods

A literature search was performed using the Web of Science database to identify TIS-related studies, and CiteSpace and VOSviewer were used for analysis and visualization. Additionally, PubMed databases were searched with subject terms and keywords to explore the development, evolution, and application of TIS technology in neurorestoratology.

Results and conclusions

A total of 127 relevant publications were included in the bibliometric analysis. Since the TIS technique was introduced in 2017, the number of related studies has grown annually. The United States and China lead in TIS research output. “Deep brain stimulation” is the most common keyword, highlighting the technique’s objectives and potential. The review results indicate that TIS is a safe and effective non-invasive deep brain stimulation method. Although the technology is still in the stages of computer simulations, animal studies, and small human trials, TIS is poised to become a promising tool for neurorestoratology, as the body of literature has expanded over the past 9 years.

背景和目的：时间干扰电刺激（TIES）是一种新型的、无创的神经调节技术，它有效地克服了传统经颅电刺激的深度和电场分散问题。与目前的神经修复方法相比，TIES有望实现更大的功能恢复。本研究旨在评估TIES的发展现状、趋势和热点，回顾其发展历程，探索其在神经修复学中的先进应用，为其未来的发展提供理论和实践指导。材料和方法：使用Web of Science数据库检索相关文献，使用CiteSpace和VOSviewer进行分析和可视化。此外，检索PubMed和CNKI数据库，检索主题词和关键词，探讨TIES技术在神经修复学中的发展、演变和应用。结果与结论：文献计量学分析共纳入87篇相关文献。自2017年引入TIES技术以来，相关研究数量每年都在增加。美国和中国在TIES研究产出方面处于领先地位。“深部脑刺激”是最常见的关键词，突出了这项技术的目标和潜力。综述结果表明，TIES是一种安全有效的无创脑深部电刺激方法。虽然这项技术仍处于计算机模拟、动物研究和小型人体试验阶段，但随着过去9 年文献的不断扩展，TIES有望成为一种有前途的神经康复工具。

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引用次数: 0

Alterations of brain activity in noise-exposed rats after transcutaneous auricular vagus nerve stimulation evaluated via fMRI fMRI评估噪声暴露大鼠经皮耳迷走神经刺激后脑活动的变化。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-05 Epub Date: 2026-01-14 DOI: 10.1016/j.neuroscience.2026.01.014

Nian Li , Liqin Zhang , Xu Tian , Yang Zhao , Guodong Feng , Zhiqiang Gao

This study aims to explore the role of the central nervous system network outside the auditory system in the development process of noise − induced central injury. A noise-exposed rat model was established with unilateral narrow-band noise. Auditory brainstem response (ABR) measured hearing thresholds at Click and 8, 16, 24, 32 kHz pre- and post-noise exposure. Experimental rats were split into transcutaneous auricular vagus nerve stimulation (ta-VNS) and sham subgroups for 2-week intervention. Resting-state fMRI (rs-fMRI) was performed on all groups (ta-VNS, sham, control) post-noise exposure and 2 weeks post-intervention. After noise exposure, 22 rats had elevated hearing thresholds at 8, 24, 32 kHz. fMRI revealed increased ALFF/ReHo in the entorhinal cortex, amygdalar cortex, and hippocampus, decreased values in the prelimbic cortex, basal forebrain, striatum, and cingulate cortex, and enhanced cingulate cortex-basal forebrain functional connectivity. The rats were divided into ta-VNS (n = 10) and sham (n = 12) subgroups for 2-week intervention. Compared with the control group (n = 9), both subgroups showed similar brain activation/inhibition in regions like the entorhinal cortex pre- vs. post-intervention. However, the ta-VNS group reversed noise-induced reduced neural activity in the prelimbic cortex and basal forebrain, and significantly enhanced their functional connectivity. Noise exposure increased entorhinal cortex, hippocampus, and amygdala activity in rats, potentially linked to aversive emotions and abnormal auditory memory. The prelimbic cortex-centered network may gate noise-induced aversive perception, with cingulate cortex activity/connectivity disrupted. ta-VNS may alleviate such perception by reversing reduced neural activity in gating-related regions and enhancing their connectivity, plus strengthening brainstem-limbic and brainstem-cerebellum functional links.

本研究旨在探讨听觉系统外的中枢神经系统网络在噪声性中枢损伤发生发展过程中的作用。采用单侧窄带噪声建立噪声暴露大鼠模型。听觉脑干反应（ABR）测量了噪声暴露前后在咔哒声和8、16、24、32 kHz时的听力阈值。实验大鼠分为经皮耳迷走神经刺激组（ta-VNS）和假手术组，干预2周。在噪声暴露后和干预后2 周，对各组（ta-VNS、假手术、对照组）进行静息状态功能磁共振成像（rs-fMRI）检查。噪声暴露后，22只大鼠在8、24、32 kHz时听力阈值升高。fMRI显示ALFF/ReHo在内嗅皮质、杏仁核皮质和海马中升高，在前边缘皮质、基底前脑、纹状体和扣带皮质中降低，扣带皮质-基底前脑功能连通性增强。将大鼠分为ta-VNS组（n = 10）和sham组（n = 12），干预2周。与对照组相比（n = 9），两个亚组在干预前后的内嗅皮质等区域表现出相似的大脑激活/抑制。然而，ta-VNS组逆转了噪声引起的边缘皮层和基底前脑神经活动的减少，并显著增强了它们的功能连通性。噪音暴露增加了大鼠的内嗅皮层、海马体和杏仁核的活动，这可能与厌恶情绪和异常的听觉记忆有关。以边缘皮层为中心的网络可能会抑制噪声诱导的厌恶感知，导致扣带皮层活动/连接中断。ta-VNS可能通过逆转门控相关区域减少的神经活动，增强它们的连通性，以及加强脑干-边缘和脑干-小脑的功能联系来减轻这种感觉。

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引用次数: 0

The efficacy of combination therapy versus monotherapy in patients with glioblastoma with abnormal epidermal growth factor receptor (EGFR) genes, a systematic review and network meta-analysis 联合治疗与单药治疗对表皮生长因子受体（EGFR）基因异常的胶质母细胞瘤患者的疗效，系统综述和网络荟萃分析。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-05 Epub Date: 2026-01-08 DOI: 10.1016/j.neuroscience.2025.12.064

Liding Fan , Hao Wu , Yi Zhang , Bo Yu , Junjie Feng , Yuejiao Du , Xiaokai Yan , Luhao Che , Songbai Xu , Yanhua Li

The primary objective of this study is to evaluate the efficacy of various pharmaceuticals (combination therapy versus monotherapy) in patients with glioblastoma (GB) with abnormal epidermal growth factor receptor (EGFR) genes. Clinical trials to investigate the therapeutic effects of different therapy was searched by PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar. The Cochrane Risk of Bias Assessment Tool and data analysis software will be applied. Data collection spanned from the earliest available date up to April 2025. Eight studies involving a total of 2,137 individuals were included, with 657 of these receiving combination therapies and 1,480 receiving monotherapies. The analysis revealed that combination therapies generally demonstrated superior efficacy compared to the single ones, while monotherapies exhibited greater potency than temozolomide (TMZ). In terms of median progression-free survival (PFS), the combinations of Afatinib plus TMZ (SUCRA: 62.28%), rindopepimut (CDX-110) plus TMZ (SUCRA: 62.27%), and depatuxizumab mafodotin (Depatux M) plus TMZ (SUCRA: 54.4%) ranked among the top tier. For median overall survival (OS), the combinations of CDX-110 plus TMZ (SUCRA: 68.8%), Depatux M plus TMZ (SUCRA: 68.3%), and Nimotuzumab plus TMZ (SUCRA: 52.5%) were positioned in the upper echelon. In terms of prolonging both median PFS and median OS in GB, CDX-110 plus TMZ and Depatux M plus TMZ have shown slightly better than comparable therapies. However, further clinical trials are needed to confirm the effectiveness of other drugs in this respect.

本研究的主要目的是评估各种药物（联合治疗与单一治疗）对表皮生长因子受体（EGFR）基因异常的胶质母细胞瘤（GB）患者的疗效。通过PubMed， Embase, Web of Science， Cochrane Library和谷歌Scholar检索临床试验以研究不同疗法的治疗效果。应用Cochrane偏倚风险评估工具和数据分析软件。数据收集的时间跨度从最早的可用日期一直到2025年4月。8项研究共纳入2137人，其中657人接受联合治疗，1480人接受单一治疗。分析显示，与单一治疗相比，联合治疗通常表现出更好的疗效，而单一治疗表现出比替莫唑胺（TMZ）更强的效力。在中位无进展生存期（PFS）方面，Afatinib + TMZ （SUCRA: 62.28%）、rindopepimut (CDX-110) + TMZ （SUCRA: 62.27%）和depatuzumab mafodotin (Depatux M) + TMZ （SUCRA: 54.4%）的组合位居前列。在中位总生存期（OS）方面，CDX-110 + TMZ （SUCRA: 68.8%）、Depatux M + TMZ （SUCRA: 68.3%）和尼莫单抗+ TMZ （SUCRA: 52.5%）的组合处于较高水平。在延长GB患者的中位PFS和中位OS方面，CDX-110 + TMZ和Depatux M + TMZ的治疗效果略好于同类治疗。然而，需要进一步的临床试验来证实其他药物在这方面的有效性。

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引用次数: 0

Neurobiological and psychosocial mechanisms linking early life stress to the pathogenesis of eating disorders 将早期生活压力与饮食失调的发病机制联系起来的神经生物学和社会心理机制。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-05 Epub Date: 2026-01-10 DOI: 10.1016/j.neuroscience.2026.01.008

Amanda Gollo Bertollo , Camila Ferreira Puntel , Hans Fiedler Bastos Rievers , Eric Gabriel Serpa Brunhara , Zuleide Maria Ignácio

Early life stress (ELS) is a significant factor in the development of eating disorders (ED), not as a single cause, but as a powerful influence that creates a vulnerability across an individual’s biology and psychology. This review explains how various forms of ELS, such as trauma, neglect, and chronic adversity, can permanently alter brain systems. For example, chronic stress hormone exposure can dysregulate the hypothalamic–pituitary–adrenal (HPA) axis, leading to abnormal cortisol levels and impaired stress self-regulation later in life. This dysregulation can lead to difficulties in managing emotions and coping with stress later in life. Furthermore, ELS impacts the brain’s neurochemical systems, including serotonin, dopamine, and norepinephrine, which are responsible for mood, reward, and impulse control. Lasting changes to these systems can explain why some people use food to cope with distress, leading to behaviors like binge eating or extreme restriction. ELS also leaves a biological memory via epigenetic modifications, notably DNA methylation, altering gene expression without changing the DNA sequence to link early experiences to long-term risk. From a psychological perspective, ELS often leads to low self-esteem, self-criticism, and an impaired ability to regulate emotions. These psychological traits, along with a person’s neurobiological profile, can make them more susceptible to developing an eating disorder as a way to gain a sense of control over their lives. By integrating genetic, epigenetic, neurobiological, and psychosocial factors, this review clarifies how ELS acts as a multifaceted embedder of vulnerability, contributing to the onset and persistence of EDs.

早期生活压力（ELS）是饮食失调（ED）发展的一个重要因素，不是一个单一的原因，而是一个强大的影响，在个体的生理和心理上造成脆弱性。这篇综述解释了各种形式的ELS，如创伤、忽视和慢性逆境，如何永久性地改变大脑系统。例如，慢性应激激素暴露会使下丘脑-垂体-肾上腺（HPA）轴失调，导致皮质醇水平异常，并在以后的生活中损害应激自我调节。这种失调会导致在以后的生活中难以管理情绪和应对压力。此外，ELS还会影响大脑的神经化学系统，包括血清素、多巴胺和去甲肾上腺素，它们负责情绪、奖励和冲动控制。这些系统的持续变化可以解释为什么有些人用食物来应对痛苦，导致暴饮暴食或极端限制等行为。ELS还通过表观遗传修饰留下生物记忆，特别是DNA甲基化，改变基因表达，而不改变DNA序列，将早期经历与长期风险联系起来。从心理学的角度来看，ELS通常会导致低自尊、自我批评和调节情绪的能力受损。这些心理特征，以及一个人的神经生物学特征，会使他们更容易患上饮食失调症，从而获得对生活的控制感。通过整合遗传、表观遗传、神经生物学和社会心理因素，本综述阐明了ELS如何作为脆弱性的多方面嵌入者，促进了EDs的发病和持续。

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引用次数: 0