Neuroscience最新文献_第5页

Cannabinoids and cognition in Parkinson's disease: Insights from animal models and emerging clinical evidence. 大麻素和帕金森病的认知：来自动物模型和新出现的临床证据的见解。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-19 DOI: 10.1016/j.neuroscience.2026.03.023

Valentina F Kitchigina, Liubov Shubina

Parkinson's disease (PD) is a progressive, multisystem neurodegenerative disorder characterized not only by motor impairments but also by a broad spectrum of debilitating non-motor symptoms, including cognitive decline. The cognitive function depends on neuronal plasticity, which is tightly regulated by multiple signaling systems, among which the endocannabinoid system (ECS) plays a significant role. Over the past three decades, substantial evidence has accumulated regarding how endogenous cannabinoids, plant-derived cannabinoids, and pharmacological modulators of ECS signaling influence synaptic plasticity, neuronal excitability, and neuroinflammation - processes that are critical in PD pathophysiology. This narrative review synthesizes experimental and clinical evidence on the effects of cannabinoid compounds on cognition in preclinical PD models and patients. Available clinical data are limited, heterogeneous, and often underpowered, with cognition frequently assessed as a secondary outcome. Observed variability in cognitive effects likely reflects differences in cannabinoid formulation, dose and treatment duration, study design, patient characteristics, and the use of heterogeneous cognitive endpoints across studies. Cannabinoid-based interventions hold promise for preserving neural circuits and modulating cognitive function in PD; however, well-designed, mechanism-informed trials with standardized, domain-specific cognitive endpoints are essential before clinical recommendations can be made.

帕金森病（PD）是一种进行性、多系统神经退行性疾病，不仅以运动障碍为特征，还以广泛的非运动症状为特征，包括认知能力下降。认知功能依赖于神经元的可塑性，神经元的可塑性受多种信号系统的严格调控，其中内源性大麻素系统（ECS）起着重要作用。在过去的三十年里，关于内源性大麻素、植物衍生大麻素和ECS信号的药理调节剂如何影响突触可塑性、神经元兴奋性和神经炎症的大量证据已经积累起来，这些过程在PD病理生理中至关重要。本文综述了大麻素化合物对临床前PD模型和患者认知影响的实验和临床证据。可获得的临床数据有限、不一致且常常缺乏说服力，认知能力经常被评估为次要结果。观察到的认知效应变异性可能反映了大麻素配方、剂量和治疗持续时间、研究设计、患者特征以及研究中异质认知终点的使用的差异。以大麻素为基础的干预措施有望保护PD患者的神经回路和调节认知功能；然而，在提出临床建议之前，设计良好、机制明确、具有标准化、特定领域认知终点的试验是必不可少的。

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引用次数: 0

Impact of P-glycoprotein substrates on transendothelial transport of amyloid-β peptide in an in vitro model. p -糖蛋白底物对淀粉样蛋白-β肽经内皮转运的影响

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-18 DOI: 10.1016/j.neuroscience.2026.03.020

Joseph Asante, Steven W Barger

Alzheimer's disease (AD) is a pervasive neurodegenerative disorder and the leading cause of dementia, strongly associated with amyloid β-peptide (Aβ) accumulation in the cerebrum. In most cases, this aggregation is primarily due to inefficiencies in the degradation and clearance of Aβ, notably its transport across the blood-brain barrier (BBB) into the bloodstream. This study investigates the role of P-glycoprotein (P-gp), a key transporter in transporting Aβ across endothelial-cell monolayers, focusing on the effects of other P-gp substrates on this process. In vitro models of the endothelial vessel wall were tested in monoculture and non-contact coculture techniques, optimizing conditions to enhance barrier integrity, as assessed by transendothelial electrical resistance (TEER) and dextran leakage assays. The hCMEC/D3 cell line was compared to primary human brain microvascular endothelial cells (HBMEC); the latter exhibited greater barrier integrity. Conditions of cell density and days in culture were optimized. The transport of fluorescently labeled Aβ_1-40 was tested in the presence of P-gp substrates digoxin, lansoprazole, atorvastatin, and mirabegron. Atorvastatin, digoxin, and lansoprazole significantly increased Aβ efflux, while mirabegron inhibited it, effects qualitatively consistent with the risk for AD associated with their administration to human patients. These findings demonstrate the potential of P-gp substrates to differentially impact Aβ transport, providing therapeutic implications for AD.

阿尔茨海默病（AD）是一种普遍的神经退行性疾病，是痴呆症的主要原因，与大脑中淀粉样β肽（a β）的积累密切相关。在大多数情况下，这种聚集主要是由于Aβ的降解和清除效率低下，特别是其通过血脑屏障（BBB）进入血液的运输。本研究探讨了p -糖蛋白（P-gp）的作用，p -糖蛋白是内皮细胞单层转运β的关键转运蛋白，重点研究了其他P-gp底物对这一过程的影响。采用单培养和非接触式共培养技术对体外内皮血管壁模型进行测试，优化条件以增强屏障完整性，并通过跨内皮电阻（TEER）和葡聚糖泄漏试验进行评估。将hCMEC/D3细胞系与原代人脑微血管内皮细胞（HBMEC）进行比较；后者表现出更大的屏障完整性。优化了细胞密度和培养天数的条件。在P-gp底物地高辛、兰索拉唑、阿托伐他汀和米拉贝隆存在的情况下，检测荧光标记的Aβ1-40的转运。阿托伐他汀、地高辛和兰索拉唑显著增加了Aβ外排，而米拉贝隆则抑制了Aβ外排，其效果与人类患者服用阿托伐他汀、地高辛和兰索拉唑的AD风险在质量上一致。这些发现证明了P-gp底物对Aβ转运的差异性影响，为AD的治疗提供了潜在的意义。

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引用次数: 0

Unravelling the impact on attention and emotions on neurophysiological responses to a multisensory experience of nature 揭示对自然的多感官体验对注意力和情绪的神经生理反应的影响

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-17 Epub Date: 2026-01-26 DOI: 10.1016/j.neuroscience.2026.01.034

Damien Gabriel , Pierre-Edouard Billot , Sylvie Tufeu , Eric Fernandez , Stéphanie Brédif , Florine Maylié , Karena Moretto , Virginie Fera , Julie Giustiniani

Exposure to natural environments has been linked to improved well-being, reduced stress, and enhanced attention. This study examined neurophysiological and behavioral effects of multisensory nature exposure (visual, auditory, and olfactory) compared to urban environments. Thirty-two right-handed women (25–49 years) performed a Go/No-Go task while EEG, electrodermal activity (EDA), and heart rate (HR) were recorded. Participants experienced images alone, images with sounds, images with odors, and images with both sounds and odors. Behavioral results showed improved task performance in natural environments, with more correct responses. However, odor-enriched conditions increased errors, suggesting that olfactory inputs may interfere with attention. Psychophysiological measures indicated lower skin conductance response (SCR) frequency in natural environments, especially under multisensory stimulation, consistent with reduced sympathetic arousal. EEG data revealed clear neural differences: the P1-N1 complex, linked to attentional effort, had greater amplitude in urban contexts, while the early posterior negativity (EPN), related to emotional processing, was stronger in natural conditions. Source localization associated EPN effects with the right occipital and inferior frontal gyrus. These findings support Attention Restoration Theory (ART) and Stress Reduction Theory (SRT), highlighting nature’s restorative potential. Sensory enrichment appeared to strengthen emotional engagement while modulating attentional performance. Results emphasize the value of multisensory perspectives in environmental neuroscience and point to EEG biomarkers as sensitive indicators of cognitive and affective processes. Future work should extend these insights to real-world settings using mobile neurophysiological methods.

暴露在自然环境中可以改善幸福感，减少压力，提高注意力。本研究考察了与城市环境相比，多感官自然暴露（视觉、听觉和嗅觉）对神经生理和行为的影响。32名右撇子女性（25-49岁）在执行Go/No-Go任务的同时记录脑电图、皮肤电活动（EDA）和心率（HR）。参与者分别体验了单独的图像、有声音的图像、有气味的图像以及既有声音又有气味的图像。行为结果显示，在自然环境中，任务表现得到改善，反应更正确。然而，气味丰富的环境会增加错误，这表明嗅觉输入可能会干扰注意力。心理生理学测量表明，在自然环境中，特别是在多感觉刺激下，皮肤电导反应（SCR）频率较低，与交感神经觉醒降低一致。脑电图数据显示了明显的神经差异：与注意力努力相关的P1-N1复合物在城市环境中振幅更大，而与情绪处理相关的早期后验负性（EPN）在自然环境中更强。源定位与EPN对右侧枕回和额下回的影响相关。这些发现支持了注意力恢复理论（ART）和压力减轻理论（SRT），强调了自然的恢复潜力。感觉丰富似乎在调节注意力表现的同时加强了情感投入。结果强调了多感官视角在环境神经科学中的价值，并指出脑电图生物标志物是认知和情感过程的敏感指标。未来的工作应该使用移动神经生理学方法将这些见解扩展到现实世界。

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引用次数: 0

Bibliometric analysis of neuroinflammation in Alzheimer’s Disease: Insights from APP/PS1 mouse model research in the past two decades 阿尔茨海默病神经炎症的文献计量学分析：过去二十年APP/PS1小鼠模型研究的见解

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-17 Epub Date: 2026-01-20 DOI: 10.1016/j.neuroscience.2026.01.020

Li Yan , Haibin Wang , Jianrong Shi , Hongsheng Tan , Qing Liu

Background: The APP/PS1 transgenic mouse is a foundational model in Alzheimer’s disease (AD) research, particularly for investigating the pivotal role of neuroinflammation in disease pathogenesis. Although substantial experimental work has explored inflammatory mechanisms in AD, the field still lacks a comprehensive overview of how research hotspots have evolved, which key scientific questions remain unresolved, and how global research efforts align with existing mechanistic gaps. Therefore, this investigation systematically evaluated scholarly trends, geographic contributions, institutional productivity, and thematic evolution to synthesize actionable insights that will guide subsequent experimental designs.

Methods: Bibliometric analysis was conducted on peer-reviewed articles indexed in the Web of Science Core Collection (2005–2024). Analytical tools, including VOSviewer, CiteSpace, and Bibliometrix, were employed to quantify research output, collaborative networks, citation metrics, and keyword co-occurrence patterns.

Results: Annual publication numbers exhibited exponential growth post-2015, reflecting an intensified focus on neuroinflammatory mechanisms in AD. China and the United States contributed 83.4 % of total publications, with the University of Barcelona as the most productive institution. High-impact journals such as Nature, Nature Neuroscience, and Brain Behavior Immunity. The analysis identified key scientific issues and evolving research fronts, with current hot topics focusing on oxidative stress, activated microglia releasing inflammatory cytokines, and abnormal autophagy-lysosome pathways.

Conclusion: The APP/PS1 mice have a significantly enhanced mechanistic understanding of neuroimmune interactions in AD pathogenesis. Future research should explore microglia-mediated neuroinflammation and brain-gut microbiome interactions to uncover novel diagnostic and therapeutic strategies for AD. This study offers an evidence-based framework to guide researchers using APP/PS1 mice model.

背景：APP/PS1转基因小鼠是阿尔茨海默病（AD）研究的基础模型，特别是研究神经炎症在疾病发病机制中的关键作用。尽管大量的实验工作已经探索了阿尔茨海默病的炎症机制，但该领域仍然缺乏对研究热点如何演变的全面概述，哪些关键科学问题尚未解决，以及全球研究工作如何与现有的机制差距保持一致。因此，本研究系统地评估了学术趋势、地理贡献、制度生产力和专题演变，以综合可操作的见解，指导后续的实验设计。方法：对Web of Science Core Collection（2005-2024）收录的同行评议文章进行文献计量分析。利用VOSviewer、CiteSpace和Bibliometrix等分析工具对研究产出、合作网络、引文指标和关键词共现模式进行量化。结果：2015年后，年度出版物数量呈指数级增长，反映了对阿尔茨海默病神经炎症机制的加强关注。中国和美国贡献了83.4 %的总出版物，其中巴塞罗那大学是最多产的机构。高影响力期刊，如《自然》、《自然神经科学》和《脑行为免疫》。分析确定了关键的科学问题和不断发展的研究前沿，目前的热门话题集中在氧化应激、激活的小胶质细胞释放炎症细胞因子和异常的自噬-溶酶体途径。结论：APP/PS1小鼠对阿尔茨海默病发病过程中神经免疫相互作用机制的认识显著增强。未来的研究应该探索小胶质细胞介导的神经炎症和脑-肠微生物组的相互作用，以发现新的AD诊断和治疗策略。本研究为APP/PS1小鼠模型的研究提供了一个循证框架。

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引用次数: 0

A multi-view DTI feature fusion framework for enhanced diagnosis of Alzheimer’s disease 一种用于阿尔茨海默病增强诊断的多视图DTI特征融合框架

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-17 Epub Date: 2026-01-20 DOI: 10.1016/j.neuroscience.2026.01.024

Jianping Qiao , Guangchao Zhou , Shaoqi Wu , Hao Shang , Qi Yuan , Jiande Sun

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder. Diffusion tensor imaging (DTI) is widely used to detect brain alterations for diagnosis, but most methods rely on single-scale information. Therefore, this study proposes the multi-view feature learning framework incorporating residual block-based 3D convolutional neural network (3D-CNN) for AD diagnosis. First, tract-based spatial statistics were applied to extract voxel-based features from fractional anisotropy (FA) and mean diffusivity (MD) maps. Second, the residual block-based 3D-CNN model was employed to extract high-level deep features, enhancing model ability to capture global contextual information. Third, fiber tracking was used to construct structural connectivity networks, which served as connectivity-based features. Fourth, radiomics was applied to extract texture and shape features from FA and MD images. These four types of features were linearly combined and subsequently reduced in dimensionality using the ReliefF algorithm. Finally, an ensemble learning strategy was employed to perform three binary classification tasks among the AD, mild cognitive impairment (MCI), and normal control (NC) groups. Additionally, layer-wise relevance propagation (LRP) was utilized to improve the interpretability of the 3D-CNN model. Evaluated on 427 subjects from the Alzheimer’s Disease Neuroimaging Initiative database, the framework integrates complementary multi-scale information, achieving superior performance. For the AD vs. NC classification, it attained an accuracy of 97.6%, a sensitivity of 98.0%, and an area under the curve of 0.964, outperforming several state-of-the-art methods. These results demonstrate that our approach enhances diagnostic accuracy and contributes to understanding disease mechanisms by identifying multi-scale biomarkers associated with known AD pathology.

阿尔茨海默病（AD）是一种不可逆的神经退行性疾病。弥散张量成像（Diffusion tensor imaging， DTI）被广泛用于检测大脑病变的诊断，但大多数方法依赖于单尺度信息。因此，本研究提出了基于残差块的3D卷积神经网络（3D- cnn）的多视图特征学习框架，用于AD诊断。首先，应用基于束的空间统计方法从分数各向异性（FA）和平均扩散率（MD）地图中提取基于体素的特征；其次，采用基于残差分块的3D-CNN模型提取高级深度特征，增强模型捕捉全局上下文信息的能力；第三，利用光纤跟踪构建结构连接网络，作为基于连接的特征。第四，应用放射组学技术提取FA和MD图像的纹理和形状特征。这四种类型的特征线性组合，随后使用ReliefF算法降维。最后，采用集成学习策略在AD组、轻度认知障碍组（MCI）和正常对照组（NC）中执行三个二元分类任务。此外，利用分层相关传播（LRP）来提高3D-CNN模型的可解释性。对来自阿尔茨海默病神经影像学倡议数据库的427名受试者进行评估，该框架整合了互补的多尺度信息，取得了卓越的性能。对于AD和NC分类，它的准确率为97.6%，灵敏度为98.0%，曲线下面积为0.964，优于几种最先进的方法。这些结果表明，我们的方法提高了诊断准确性，并有助于通过识别与已知AD病理相关的多尺度生物标志物来理解疾病机制。

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引用次数: 0

Neonatal quercetin exposure reduces motor impairments and cerebellar damage in cerebral palsy rats, with different effects on males and females 新生儿接触槲皮素可减少脑瘫大鼠的运动损伤和小脑损伤，但对雄性和雌性的影响不同。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-17 Epub Date: 2026-01-19 DOI: 10.1016/j.neuroscience.2026.01.023

Glayciele Leandro de Albuquerque , Raul Manhães-de-Castro , Isla Ariadny Amaral De Souza Gonzaga Paz , Eulália Rebeca da Silva-Araújo , Henrique José Cavalcanti Bezerra Gouveia , Maria Letícia Farias Tenório , Marcos Antônio da Silva Araújo , Ana Elisa Toscano

Cerebral palsy (CP) comprises a group of neuromusculoskeletal disorders resulting from fetal or infant brain injury. Quercetin has demonstrated antioxidant, anti-inflammatory and neuroprotective properties in neurological diseases. This study aimed to evaluate the effects of neonatal treatment with quercetin on motor development, neuronal loss, and inflammation in the cerebellum of rats subjected to CP. CP model was induced by postnatal anoxia (P0 and P1) and hindlimbs sensorimotor restriction (P2 to P28). Quercetin (10 mg/kg) was administered intraperitoneally from P2 to P22. Animals were analyzed for somatic growth; reflex ontogenesis; muscle strength; motor coordination; locomotor activity and gait in CatWalk; neuronal loss and inflammation in the cerebellum. Experimental CP, regardless of sex, restricted body weight gain, somatic growth, soleus muscle weight, muscle strength, motor coordination, locomotor activity and gait development, and promoted increased neuroinflammation in the cerebellum. Neonatal quercetin exposure was positive in the model of CP in males, favoring body weight gain, reducing the presence of primitive reflexes, increasing muscle strength, improving exploratory capacity in the open field, decreasing the time in the swing phase during gait, and reducing the expression of TNF in the cerebellum. In females, quercetin had a protective effect by stimulating somatic growth, favoring the regularity of steps during gait, and preventing neuronal loss in the cerebellum of CP animals. This study suggests a greater responsiveness in males compared to females, and indicates a possible protective role of quercetin in both sexes in motor development and neuroinflammation in CP models.

脑瘫（CP）包括一组由胎儿或婴儿脑损伤引起的神经肌肉骨骼疾病。槲皮素在神经系统疾病中具有抗氧化、抗炎和神经保护作用。本研究旨在探讨新生儿期槲皮素对CP大鼠运动发育、神经元丢失和小脑炎症的影响。采用产后缺氧（P0和P1）和后肢感觉运动受限（P2 ~ P28）诱导CP模型。从P2至P22腹腔注射槲皮素（10 mg/kg）。对动物进行体生长分析；反射个体发育;肌肉力量;运动协调;猫步的运动活动和步态；小脑的神经元丢失和炎症。实验CP，不分性别，限制体重增加、体生长、比目鱼肌重量、肌肉力量、运动协调、运动活动和步态发育，并促进小脑神经炎症增加。新生儿槲皮素暴露在雄性CP模型中呈阳性，有利于体重增加，减少原始反射的存在，增加肌肉力量，提高开阔区域的探索能力，减少步态中摇摆阶段的时间，降低小脑中TNF的表达。在雌性CP动物中，槲皮素通过刺激体细胞生长、促进步态的规律性和防止小脑的神经元丢失而具有保护作用。这项研究表明，与女性相比，男性的反应性更强，并表明槲皮素在CP模型的运动发育和神经炎症中可能具有保护作用。

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引用次数: 0

A Mendelian randomization study with bioinformatics analysis reveals gut microbiota mediates in heart failure and Alzheimer’s disease via BAFF-R 一项孟德尔随机研究和生物信息学分析显示，肠道微生物群通过BAFF-R介导心力衰竭和阿尔茨海默病。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-17 Epub Date: 2026-01-22 DOI: 10.1016/j.neuroscience.2026.01.021

Lv Zhou , Zhitian Wang , Ying Jiang , Mengxue Wang , Xiaoli Li , Qingguo Ren

Background

The causal relationship between heart failure (HF) and Alzheimer’s Disease (AD) is still debated, and the mechanisms underlying AD caused by HF are still not fully understood.

Methods

This study aimed to explore the potential genetic causality between HF and AD using two-sample Mendelian randomization (MR) study. The investigation was extended with mediation MR to explore the underlying genetic mechanisms. Bioinformatics analysis provided additional evidence.

Results

In our investigation, we harnessed a two-sample MR method to delineate a causal relationship between HF and AD, uncovering a significant positive association. Our results, derived from a meticulous two-step MR analysis, have shed new light on the mediating role of gut microbiota (GM) within the HF-AD interplay. Notably, we identified specific metabolic pathways with substantial correlations: a pivotal super-pathway crucial for the biosynthesis of branched chain amino acids (BCAAs) and the pyrimidine deoxyribonucleotides de novo biosynthesis II pathway. Our findings extend beyond the metabolic, revealing the ’BAFF-R on CD20-’ immune cells as key mediators in the GM-AD pathway. Bioinformatics analysis revealed significant enrichment of common differentially expressed genes between HF and AD in immune-related pathways.

Conclusions

We present a thorough genetic analysis of the relationship between HF, AD, and the intestinal-neuroimmune interaction, emphasizing the potential of GM and immune cells as therapeutic targets.

背景：心力衰竭（HF）与阿尔茨海默病（AD）之间的因果关系仍存在争议，HF引起AD的机制仍未完全了解。方法：采用双样本孟德尔随机化（MR）研究，探讨HF与AD之间潜在的遗传因果关系。通过调解磁共振扩展了调查，以探索潜在的遗传机制。生物信息学分析提供了额外的证据。结果：在我们的研究中，我们利用双样本MR方法来描述HF和AD之间的因果关系，发现了显著的正相关。我们的研究结果来源于细致的两步磁共振分析，揭示了肠道微生物群（GM）在HF-AD相互作用中的介导作用。值得注意的是，我们确定了具有实质性相关性的特定代谢途径：支链氨基酸（BCAAs）生物合成的关键超途径和嘧啶脱氧核糖核苷酸从头合成II途径。我们的发现超越了代谢，揭示了“CD20-上的BAFF-R”免疫细胞是GM-AD通路的关键介质。生物信息学分析显示，HF和AD在免疫相关通路上的共同差异表达基因显著富集。结论：我们对HF、AD和肠道-神经免疫相互作用之间的关系进行了全面的遗传学分析，强调了转基因和免疫细胞作为治疗靶点的潜力。

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引用次数: 0

Short-term high-fat diet impairs anterograde and retrograde memory consolidation, but not retrieval in aged rats 短期高脂肪饮食损害老年大鼠的顺行和逆行记忆巩固，但不影响检索。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-17 Epub Date: 2026-01-28 DOI: 10.1016/j.neuroscience.2026.01.028

Bryan D. Alvarez , Jayden D. Milligan , Zoha H. Khan , Ruth M. Barrientos

Background

Aging increases vulnerability to cognitive decline, and ultraprocessed diets high in saturated fat may accelerate this trajectory. Although short-term high-fat diet (HFD) exposure is known to impair memory in aged animals, the specific stages of memory most susceptible to short-term HFD remain unclear.

Methods

This study examined how short-term HFD influences anterograde consolidation, retrograde consolidation, and retrieval of long-term fear memory in aged rats. Male F344 × BN F1 rats (22–24 months) consumed chow or three days of HFD provided at distinct times relative to contextual and cued fear conditioning to isolate each memory phase. Importantly, this brief HFD protocol minimizes metabolic disturbances typically produced by longer-term diet manipulation, allowing us to isolate the effects of macronutrient composition on memory processes.

Results

Three days of HFD before or immediately after conditioning significantly impaired contextual and cued fear memory, reflecting disrupted anterograde and retrograde consolidation. In contrast, three days of HFD before retrieval had no effect on memory performance.

Conclusion

These findings demonstrate that short-term consumption of ultraprocessed HFD selectively impairs consolidation while sparing retrieval of hippocampal- and amygdala-dependent memory in aging. These findings are important because identifying the specific memory processes that are disrupted, rather than global memory dysfunction, helps narrow mechanistic targets and informs the development of more precise interventions to mitigate diet-related cognitive decline in aging.

背景：衰老增加认知能力下降的脆弱性，高饱和脂肪的超加工饮食可能加速这一轨迹。虽然已知短期高脂肪饮食（HFD）暴露会损害老年动物的记忆，但最容易受到短期高脂肪饮食影响的记忆的具体阶段仍不清楚。方法：研究短期HFD对老年大鼠长期恐惧记忆的顺行巩固、逆行巩固和恢复的影响。雄性F344 × BN F1大鼠（22-24 个月）在不同的时间消耗相对于情境和暗示恐惧条件反射提供的食物或三天的HFD来隔离每个记忆阶段。重要的是，这个简短的HFD方案最大限度地减少了通常由长期饮食控制产生的代谢紊乱，使我们能够分离出宏量营养素组成对记忆过程的影响。结果：在条件反射之前或之后的三天，HFD显著损害了情境和线索恐惧记忆，反映了逆行和逆行巩固的中断。相比之下，检索前三天的HFD对记忆性能没有影响。结论：这些研究结果表明，短期食用超加工的HFD选择性地损害了衰老过程中海马和杏仁核依赖性记忆的巩固，同时保留了记忆的恢复。这些发现很重要，因为确定被破坏的特定记忆过程，而不是全局记忆功能障碍，有助于缩小机制目标，并为开发更精确的干预措施提供信息，以减轻与饮食有关的认知衰退。

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引用次数: 0

Epigenetic regulation of aggression-linked genes following prenatal stress enhances risk for sexual aggression in male rat offspring 产前应激后攻击相关基因的表观遗传调控增加了雄性大鼠后代性攻击的风险。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-17 Epub Date: 2026-01-25 DOI: 10.1016/j.neuroscience.2026.01.033

Elvis Mbiydzenyuy Ngala , Sian Megan Joanna Hemmings , Jacqueline Samantha Womersley , Tarryn Willmer , Thando W. Shabangu , Lihle Qulu-Appiah

Early-life psychosocial adversity can shape adult behaviour through enduring epigenetic mechanisms, yet the neurobiological pathways linking parental stress to offspring socio-affective behaviour remain incompletely understood. Here, we investigated whether paternal social isolation and maternal prenatal stress are associated with persistent DNA methylation differences in aggression- and stress-related neurochemical receptor genes in male rat offspring, and whether these molecular alterations co-occur with changes in aggression-like and maladaptive mating behaviour. Male Wistar rats were generated from F0 males housed either in groups or in social isolation and from dams exposed to prenatal restraint stress or control conditions. In adulthood, male offspring were assessed for aggression-like behaviour using the resident–intruder test and for maladaptive mating attempts toward non-receptive females using the Sexual Aggression Test, a rodent paradigm capturing forced or inappropriate mating behaviour. Targeted DNA methylation profiling of the androgen receptor, corticotropin-releasing hormone receptor 1, oxytocin receptor, and serotonin receptor 1A genes was performed using pyrosequencing in the amygdala, hippocampus, hypothalamus, and prefrontal cortex. Paternal social isolation was associated with increased methylation of stress- and androgen-related genes in limbic and prefrontal regions, whereas prenatal stress was linked to region-specific alterations in oxytocinergic and serotonergic gene methylation. These epigenetic patterns co-occurred with heightened aggression-like behaviour and increased maladaptive mating attempts in offspring from stress-exposed lineages. Despite modest methylation effects and model limitations, the findings suggest paternal and prenatal stress jointly shape offspring socio-affective behaviour through region-specific epigenetic variation.

早期生活中的社会心理逆境可以通过持久的表观遗传机制塑造成年后的行为，然而，将父母压力与后代社会情感行为联系起来的神经生物学途径仍然不完全清楚。在这里，我们研究了父亲的社会隔离和母亲的产前压力是否与雄性大鼠后代中攻击和压力相关的神经化学受体基因的持续DNA甲基化差异有关，以及这些分子改变是否与攻击样和适应不良的交配行为的变化共同发生。雄性Wistar大鼠是由群体饲养或社会隔离的母鼠和暴露于产前约束压力或控制条件下的母鼠产生的。成年后，研究人员使用“常驻入侵者”测试评估雄性后代的攻击性行为，并使用“性侵犯测试”评估雄性后代对不接受交配的雌性的不适应交配尝试。利用焦磷酸测序技术对杏仁核、海马、下丘脑和前额皮质的雄激素受体、促肾上腺皮质激素释放激素受体1、催产素受体和血清素受体1A基因进行靶向DNA甲基化分析。父亲的社会隔离与边缘和前额叶区域压力和雄激素相关基因甲基化增加有关，而产前压力与催产素和血清素能基因甲基化的区域特异性改变有关。这些表观遗传模式与来自压力暴露谱系的后代的攻击性行为增强和适应不良的交配尝试增加共同发生。尽管有适度的甲基化效应和模型局限性，研究结果表明，父亲和产前压力通过区域特异性表观遗传变异共同塑造了后代的社会情感行为。

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引用次数: 0

Effects of different noisy galvanic vestibular stimulation frequencies on postural control responses 不同噪声前庭电刺激频率对体位控制反应的影响。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-03-17 Epub Date: 2026-01-28 DOI: 10.1016/j.neuroscience.2026.01.032

Tsubasa Mitsutake , Motomichi Sonobe

Noisy galvanic vestibular stimulation (nGVS) can improve postural stability by delivering subthreshold electrical noise to the vestibular system. However, the frequency-specific effects of nGVS on postural control responses—particularly those involving the center of mass (COM) recovery force and movement strategies—remain unclear. We investigated how different nGVS frequencies affect postural control, estimating COM fluctuations using a rigid pendulum model. Thirty-two healthy adults (mean age, 20.3 ± 1.2 years; 19 females) underwent three interventions: sham nGVS, low-frequency nGVS (LF-nGVS, 0–100 Hz), or high-frequency nGVS (HF-nGVS, 100–640 Hz), each with a 200 µA current (0 µA for the sham). During each 40-s trial, participants stood on a platform with eyes closed and the middle 30 s were analyzed. Inertial measurement units were affixed to the occipital protuberance to capture head kinematics. Postural control was assessed using conventional metrics (e.g., center of foot pressure [COP], COM sway, and head acceleration) and novel indicators of COM recovery force and head acceleration control based on motor strategies. Both LF-nGVS and HF-nGVS significantly reduced several indices, including COP velocity and head angular velocity, compared with sham stimulation. No significant differences were observed between LF-nGVS and HF-nGVS. Head acceleration was significantly correlated with COM recovery force and joint movement strategies in both stimulation conditions. Although the mechanism of neural network activity at different stimulation frequencies requires careful interpretation, these findings suggest that COM recovery and associated motor strategies contribute to nGVS-induced postural improvements, providing insights into its neuromechanistic effects.

噪声前庭电刺激（nGVS）可以通过向前庭系统传递阈下电噪声来改善姿势稳定性。然而，nGVS对姿势控制反应的频率特异性影响，特别是涉及质心恢复力和运动策略的影响，仍不清楚。我们研究了不同的nGVS频率如何影响姿势控制，使用刚性摆模型估计COM波动。32名健康成年人（平均年龄20.3 ± 1.2 岁；19名女性）接受了三种干预：假性nGVS、低频nGVS（低频-nGVS， 0-100 Hz）或高频nGVS（低频-nGVS， 100-640 Hz），每种干预的电流为200µa（假性为0µa）。在每一次40秒的试验中，参与者闭着眼睛站在一个平台上，然后分析中间的30秒 。惯性测量单元被贴在枕骨突起以捕捉头部运动学。姿势控制采用常规指标（如足压力中心[COP]、头部摆动和头部加速度）和基于运动策略的头部恢复力和头部加速度控制的新指标进行评估。与假刺激相比，LF-nGVS和HF-nGVS均显著降低了COP速度和头部角速度等多项指标。LF-nGVS与HF-nGVS之间无显著差异。在两种刺激条件下，头部加速度与COM恢复力和关节运动策略显著相关。尽管不同刺激频率下神经网络活动的机制需要仔细解释，但这些发现表明，COM恢复和相关的运动策略有助于ngvs诱导的姿势改善，为其神经机制效应提供了见解。

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引用次数: 0