Neuroscience最新文献_第4页

Fiber-type-specific architecture and pathophysiology of the neuromuscular junction 神经肌肉连接处的纤维类型特异性结构和病理生理学。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-16 DOI: 10.1016/j.neuroscience.2026.01.015

Rizwan Qaisar

The neuromuscular junction (NMJ) is a specialized synapse essential for translating neuronal signals into muscle contraction. This review examines the complex structural, functional, and molecular differences in NMJs that innervate fast- and slow-twitch skeletal muscle fibers. Fast-twitch fibers, optimized for rapid and powerful contractions, possess elaborate NMJs with deep folds, high neurotransmitter turnover, and greater vulnerability to synaptic fatigue and degeneration. In contrast, slow-twitch fiber NMJs exhibit simpler but more stable architectures that support sustained, fatigue-resistant activity.

These differences are not fixed but subject to activity-dependent plasticity and pathological remodeling. Chronic stimulation, injury, and aging influence NMJ morphology, with fast-twitch junctions more prone to degeneration in conditions such as ALS, myasthenia gravis, and diabetic neuropathy. Slow-twitch NMJs often resist early deterioration due to superior trophic support, metabolic stability, and more robust expression of synaptic organizers, such as agrin and PGC-1α.

Several key signaling pathways, including agrin–MuSK–LRP4, Wnt/β-catenin, and neuregulin/ErbB, govern NMJ maintenance with fiber-type-specific nuances. These insights underscore the importance of tailoring therapeutic strategies to the muscle fiber phenotype. Gene therapies, neuromuscular electrical stimulation, and biomaterial scaffolds are emerging as promising modalities for preserving or restoring NMJ integrity, especially in fast-twitch fibers at higher risk of degeneration.

Understanding fiber-type-specific NMJ biology enhances our understanding of motor control, muscle aging, and neuromuscular disease progression, and it opens pathways for precision therapeutics that target vulnerable synapses with structural and functional specificity. This review introduces a novel perspective by emphasizing fiber-type-specific NMJ differences and their implications for targeted therapies.

神经肌肉连接（NMJ）是一种特殊的突触，是将神经元信号转化为肌肉收缩所必需的。本文综述了支配快缩和慢缩骨骼肌纤维的NMJs的复杂结构、功能和分子差异。快速抽搐纤维，优化为快速和强大的收缩，具有复杂的NMJs深褶皱，高神经递质周转率，更容易受到突触疲劳和退化。相比之下，慢肌纤维NMJs表现出更简单但更稳定的结构，支持持续的抗疲劳活动。这些差异不是固定的，而是受活动依赖性可塑性和病理性重塑的影响。慢性刺激、损伤和衰老影响NMJ形态，在ALS、重症肌无力和糖尿病神经病变等情况下，快速抽搐连接更容易发生变性。由于优越的营养支持、代谢稳定性和更强的突触组织者（如agrin和PGC-1α）表达，慢抽搐NMJs通常能够抵抗早期退化。几种关键的信号通路，包括agrin-MuSK-LRP4、Wnt/β-catenin和neuregulin/ErbB，通过纤维类型特异性的细微差别控制NMJ的维持。这些见解强调了针对肌纤维表型定制治疗策略的重要性。基因疗法、神经肌肉电刺激和生物材料支架正在成为保存或恢复NMJ完整性的有希望的方式，特别是在变性风险较高的快肌纤维中。了解纤维类型特异性的NMJ生物学增强了我们对运动控制、肌肉老化和神经肌肉疾病进展的理解，并为针对结构和功能特异性的易损突触的精确治疗开辟了途径。这篇综述通过强调纤维类型特异性NMJ差异及其对靶向治疗的影响，介绍了一个新的观点。

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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 : 2026-01-14 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

Differential modulation of cognitive control by approach and avoidance motivation. 接近动机和回避动机对认知控制的差异调节。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-14 DOI: 10.1016/j.neuroscience.2026.01.006

Yan Fei Ma, Rong Cao, Jian Wang, Song Xue

The trade-off between proactive and reactive cognitive control refers to the dynamic regulation process by which individuals flexibly allocate cognitive resources according to task demands-representing a core feature of cognitive control flexibility. Previous research has shown that emotion can significantly affect this trade-off, but most studies have focused on emotional valence and arousal, lacking a systematic investigation into how emotional motivation influences the trade-off in cognitive control. Using the AX-Continuous Performance Task paradigm, the present study systematically examined the mechanisms by which different emotional motivations impact the trade-off between proactive and reactive control. Results showed that proactive control increased under both approach and avoidance motivation, as indicated by higher Proactive Control Index scores and larger CNV amplitudes than baseline. In contrast, reactive control improved only under avoidance motivation: behaviorally, avoidance enhanced BX performance, and electrophysiologically it produced a larger P3a amplitude than both approach and baseline. Approach motivation did not produce a reliable change in reactive control. These findings suggest that approach and avoidance motivation differentially modulate proactive and reactive control, thereby influencing the dynamic trade-off between cognitive control modes and revealing a regulatory process through which emotion may shape cognitive control strategy selection.

主动认知控制与被动认知控制的权衡是指个体根据任务需求灵活分配认知资源的动态调节过程，是认知控制灵活性的核心特征。先前的研究表明，情绪可以显著影响这种权衡，但大多数研究都集中在情绪效价和情绪唤醒上，缺乏对情绪动机如何影响认知控制中的权衡的系统研究。本研究采用ax -连续绩效任务范式，系统考察了不同情绪动机影响主动控制与反应控制取舍的机制。结果表明，在接近和回避动机下，主动控制指数得分和CNV振幅均高于基线。相比之下，反应性控制仅在回避动机下得到改善：行为上，回避增强了BX表现，电生理上，它比接近和基线产生更大的P3a振幅。接近动机并没有在反应性控制中产生可靠的改变。研究结果表明，趋近动机和回避动机对主动控制和反应控制的调节存在差异，从而影响认知控制模式之间的动态权衡，揭示了情绪影响认知控制策略选择的调节过程。

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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 : 2026-01-14 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

Omega-3 supplementation prevents functional and neural respiratory damage present in an animal model of Parkinson’s disease 补充Omega-3可预防帕金森病动物模型中出现的功能和神经呼吸损伤。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-14 DOI: 10.1016/j.neuroscience.2026.01.016

Taina O. Macedo , Lais M. Cabral , Nicole C. Miranda , Fulvio A. Scorza , Thiago S. Moreira , Ana C. Takakura

Parkinson’s Disease (PD) is a neurodegenerative disorder primarily characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to classical motor symptoms such as tremors, rigidity, and bradykinesia. In later stages, patients frequently develop non-classical symptoms, including respiratory dysfunctions, which may result from neurodegeneration in brainstem regions involved in respiratory control, such as the pre-Bötzinger Complex (preBötC) and the retrotrapezoid nucleus (RTN). These changes are likely driven by oxidative stress and neuroinflammation.

Given the antioxidant and anti-inflammatory properties of omega-3 polyunsaturated fatty acids, this study investigated whether omega-3 supplementation could prevent respiratory-related neuroanatomical and respiratory dysfunctional alterations in a mouse model of PD induced by bilateral injection of 6-hydroxydopamine into the striatum. Omega-3 supplementation prevented respiratory dysfunction by preventing neuronal loss in the preBötC and RTN, reducing glial reactivity and oxidative stress, and maintaining respiratory frequency. These findings support the therapeutic potential of omega-3 in mitigating respiratory dysfunction in PD.

帕金森病（PD）是一种神经退行性疾病，其主要特征是黑质中多巴胺能神经元的进行性丧失，导致典型的运动症状，如震颤、僵硬和运动迟缓。在晚期，患者经常出现非典型症状，包括呼吸功能障碍，这可能是由参与呼吸控制的脑干区域神经退行性变引起的，如pre-Bötzinger复合体（preBötC）和后梯形核（RTN）。这些变化可能是由氧化应激和神经炎症引起的。鉴于omega-3多不饱和脂肪酸的抗氧化和抗炎特性，本研究探讨了omega-3补充剂是否可以预防双侧纹状体注射6-羟多巴胺诱导的PD小鼠模型呼吸相关神经解剖学和呼吸功能障碍的改变。Omega-3补充剂通过防止preBötC和RTN中的神经元丢失，降低神经胶质反应性和氧化应激，以及维持呼吸频率来预防呼吸功能障碍。这些发现支持omega-3在缓解PD患者呼吸功能障碍方面的治疗潜力。

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引用次数: 0

The altered representation of interoceptive sensations in individuals with alexithymia: A mouse-tracking and EEG co-registration study 述情障碍患者内感受感觉表征的改变：一项小鼠追踪和脑电图联合登记研究。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-12 DOI: 10.1016/j.neuroscience.2026.01.013

Xianrui Li , Wenting Ye , Yunhong Wang , Chuyao Peng , Rui Tao , Junrong Ren , Qian Luo , Zhiting Ren , Junlai Shan , Dongtao Wei , Jiang Qiu

Humans primarily rely on bodily sensations to experience emotions. Alexithymia, however, alters individuals’ emotional experiences. Despite this, limited research has examined whether individuals with different levels of alexithymia experience the same emotions when exposed to identical bodily sensations. The present studies aimed to explore the altered representation of interoceptive sensations in individuals with alexithymia. In Study 1, we measured how participants associated interoceptive sensations with emotion categories using a computer mouse. In Study 2, event-related potentials (ERPs) were recorded simultaneously while participants performed the same task. Mouse trajectories and the N400 component were analyzed, and ANOVA was conducted to examine the differences in both mouse trajectories and N400 amplitudes. In Study 1, we found that individuals with high alexithymia (HA) exhibited less direct and more curved mouse trajectories compared to those with low alexithymia (LA). Study 2 confirmed these behavioral findings and further revealed that HA individuals exhibited greater N400 amplitudes than LA individuals. Our findings suggest that HA individuals experience deficits in the representation of interoceptive sensations, with the N400 serving as a potential index of these deficits in individuals with alexithymia.

人类主要依靠身体的感觉来体验情感。然而，述情障碍会改变个人的情感体验。尽管如此，有限的研究已经调查了不同程度述情障碍的个体在接触相同的身体感觉时是否会经历相同的情绪。本研究旨在探讨述情障碍患者内感觉表征的改变。在研究1中，我们测量了参与者如何使用电脑鼠标将内感受与情绪类别联系起来。在研究2中，当参与者执行相同的任务时，同时记录事件相关电位（erp）。对小鼠轨迹和N400分量进行分析，并采用方差分析来检验小鼠轨迹和N400振幅的差异。在研究1中，我们发现与低述情障碍（LA）相比，高述情障碍（HA）个体表现出更少的直接和更弯曲的小鼠轨迹。研究2证实了这些行为发现，并进一步揭示HA个体比LA个体表现出更大的N400振幅。我们的研究结果表明，HA个体在表征内感受性感觉方面存在缺陷，而N400可以作为述情障碍个体这些缺陷的潜在指标。

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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 : 2026-01-11 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

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 : 2026-01-10 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

Zebrafish neural regeneration: mechanistic insights into human nervous system repair 斑马鱼神经再生：人类神经系统修复的机理。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-10 DOI: 10.1016/j.neuroscience.2026.01.009

Lilesh Kumar Pradhan , Saroj Kumar Das

The zebrafish (Danio rerio) is a powerful vertebrate model for studying neurodegenerative diseases and regenerative medicine due to its genetic similarity to humans and its unique ability to regenerate the central nervous system (CNS). This review synthesizes key findings on zebrafish neural regeneration across the retina, spinal cord, and brain, emphasizing translational relevance. Zebrafish effectively model disorders such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, stroke, epilepsy, autism spectrum disorders, and CNS injuries. Unlike mammals, they restore damaged axons and recover function through a permissive extracellular matrix, transient inflammation, and glial plasticity. In the retina, Müller glia reprograms after injury to generate progenitors that replace lost neurons, regulated by Wnt/β-catenin, Shh, EGF, Hippo/YAP, and ROCK signaling. In the spinal cord, ependymo-radial glia forms a laminin- and fibronectin-rich “glial bridge,” guided by FGF and CTGF signaling, supporting axon regrowth. In the brain, GFAP- and Olig2-positive radial glia drive neurogenesis within ventricular niches, integrating new neurons while maintaining circuit integrity. Regeneration involves transient Notch suppression, context-specific Wnt and FGF activation, and immune modulation without fibrosis. Advances in single-cell RNA sequencing, CRISPR-Cas9, lineage tracing, and multi-omics have identified injury-induced progenitor states, regulators (ascl1a, lin28, sox2, stat3), and epigenetic programs enabling regeneration. Emerging research on bioelectric signaling, microbiota–brain interactions, and lipid mediators further expands systemic understanding. Overall, zebrafish provide a unified model for decoding vertebrate CNS regeneration and guiding therapeutic strategies to restore neural repair in humans.

斑马鱼（Danio rerio）是研究神经退行性疾病和再生医学的强大脊椎动物模型，因为它与人类遗传相似，并且具有再生中枢神经系统（CNS）的独特能力。这篇综述综合了斑马鱼视网膜、脊髓和大脑神经再生的关键发现，强调了翻译的相关性。斑马鱼可以有效地模拟疾病，如阿尔茨海默氏症、帕金森症、肌萎缩侧索硬化症、中风、癫痫、自闭症谱系障碍和中枢神经系统损伤。与哺乳动物不同，它们通过允许的细胞外基质、短暂的炎症和神经胶质可塑性来修复受损的轴突和恢复功能。在视网膜中，损伤后的突触神经胶质重编程产生替代丢失神经元的祖细胞，由Wnt/β-catenin、Shh、EGF、Hippo/YAP和ROCK信号调节。在脊髓中，室管膜-放射状胶质细胞形成一个层粘连蛋白和纤维连接蛋白丰富的“胶质桥”，由FGF和CTGF信号引导，支持轴突再生。在大脑中，GFAP-和olig2阳性的放射状胶质细胞驱动脑室壁龛内的神经发生，在维持回路完整性的同时整合新神经元。再生包括瞬时Notch抑制、上下文特异性Wnt和FGF激活以及无纤维化的免疫调节。单细胞RNA测序、CRISPR-Cas9、谱系追踪和多组学的进展已经确定了损伤诱导的祖细胞状态、调节因子（ascl1a、lin28、sox2、stat3）和能够再生的表观遗传程序。对生物电信号、微生物群-脑相互作用和脂质介质的新兴研究进一步扩展了对系统的理解。总的来说，斑马鱼为解码脊椎动物中枢神经系统再生和指导治疗策略提供了一个统一的模型，以恢复人类神经修复。

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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 : 2026-01-09 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