Neuroscience最新文献_第4页

Electromyography of spontaneous neuromuscular release of ACh: variations according to sex and age 神经肌肉自发释放乙酰胆碱的肌电图：性别和年龄的变化。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-22 DOI: 10.1016/j.neuroscience.2025.12.055

R. Gutierrez , M. Fibla , E. Skorupska , M.M. Santafe

Neuromuscular transmission plays a crucial role in muscle function, with differences in neurotransmitter release potentially influenced by sex and aging. While hormonal effects on neurotransmission have been studied, their impact on acetylcholine (ACh) release at the neuromuscular junction remains largely unexplored. Understanding these differences could provide insights into age-related muscle function decline and sex-specific variations in neuromuscular disorders. This study aims to investigate sex- and age-related differences in spontaneous ACh release at the neuromuscular junction in mammals, focusing on variations in electromyographic (EMG) activity. Experiments were conducted on young (2 months) and old (15 months) Swiss male and female mice. EMG recordings were taken from the gastrocnemius muscle, analyzing the percentage of sites with endplate noise, noise frequency, and spike frequency. Estrous cycle stages in female mice were identified to account for hormonal fluctuations. Males exhibited a higher percentage of sites with endplate noise than females. Old females had the highest frequency of endplate noise, while old males had the largest amplitude. Spike frequency was higher in females and increased with age. These results suggest sex and age differences in neuromuscular activity, potentially influenced by hormonal and autonomic regulation. In conclusion, neuromuscular transmission differs between sexes and across aging. Estrogens may modulate cholinergic receptor function, and autonomic nervous system activity likely contributes to observed differences. These findings highlight distinct aging patterns in neuromuscular function between males and females.

神经肌肉传递在肌肉功能中起着至关重要的作用，神经递质释放的差异可能受到性别和年龄的影响。虽然已经研究了激素对神经传递的影响，但它们对神经肌肉连接处乙酰胆碱（ACh）释放的影响在很大程度上仍未被探索。了解这些差异可以深入了解与年龄相关的肌肉功能衰退和神经肌肉疾病的性别差异。本研究旨在探讨哺乳动物神经肌肉交界处自发乙酰胆碱释放的性别和年龄相关差异，重点关注肌电图（EMG）活动的变化。实验采用幼年（2 月龄）和老年（15 月龄）瑞士雄性和雌性小鼠。取腓肠肌肌电图记录，分析终板噪声、噪声频率和尖峰频率位点的百分比。确定了雌性小鼠的发情周期阶段，以解释激素波动。尾板噪声位点雄性比雌性多。老年雌鼠尾板噪声频率最高，老年雄鼠尾板噪声振幅最大。尖峰频率在女性中较高，且随年龄增长而增加。这些结果表明，性别和年龄在神经肌肉活动方面存在差异，可能受到激素和自主调节的影响。总之，神经肌肉传递在性别和年龄之间是不同的。雌激素可能调节胆碱能受体的功能，而自主神经系统的活动可能有助于观察到的差异。这些发现突出了男性和女性神经肌肉功能的不同衰老模式。

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引用次数: 0

Apremilast-mediated protection against Aβ-induced cytotoxicity correlates with PI3K/Akt pathway activation apremilast介导的抗a β诱导的细胞毒性保护与PI3K/Akt通路激活相关。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-22 DOI: 10.1016/j.neuroscience.2025.12.054

Hao Yang , Jianping Jia

Background

Apremilast, a novel inhibitor of phosphodiesterase-4 (PDE4), has demonstrated anti-inflammatory, immunomodulatory, neuroprotective, and senolytic properties. Given these characteristics, Apremilast, similar to other PDE4 inhibitors, holds potential as a therapeutic candidate for Alzheimer’s disease (AD).

Objective

This study aims to investigate whether Apremilast can mitigate neurotoxicity induced by amyloid β (Aβ) in BV2 microglial and HT-22 hippocampal mouse cell lines, while also exploring its neuroprotective effects and the underlying molecular mechanisms.

Methods

To begin, network pharmacology was employed to identify potential shared targets between Apremilast and AD. Molecular docking was subsequently used to assess the binding affinity of Apremilast to key targets. At the cellular level, the Cell Counting Kit-8 (CCK-8) assay was conducted to evaluate Apremilast’s protective effects against Aβ-induced cytotoxicity in BV2 and HT-22 cells. Finally, Western blot (WB) analysis was performed to examine the expression of proteins in the PI3K/Akt signaling pathway, offering insights into the molecular mechanisms underlying Apremilast’s neuroprotective role.

Results

Target enrichment analysis identified several potential pathways, among which the PI3K/Akt pathway was chosen for further examination. The results showed that Apremilast effectively counteracted Aβ-induced cytotoxicity in both BV2 and HT-22 cells, leading to a significant improvement in cell viability. Moreover, Western blot analysis demonstrated an upregulation of phosphorylated Akt (p-Akt/Akt) and PI3K protein levels.

Conclusion

In conclusion, this study provides evidence that Apremilast may exert protective effects against Aβ-induced cytotoxicity in BV2 and HT-22 cells by modulating the PI3K/Akt signaling pathway. However, further validation of its dosage and efficacy in vivo is required.

背景：Apremilast是一种新型磷酸二酯酶-4 （PDE4）抑制剂，具有抗炎、免疫调节、神经保护和抗衰老的特性。鉴于这些特点，Apremilast与其他PDE4抑制剂类似，具有作为阿尔茨海默病（AD）治疗候选药物的潜力。目的：研究阿普雷米司特是否能减轻β淀粉样蛋白（Aβ）对小鼠BV2小胶质细胞和HT-22海马细胞系的神经毒性，并探讨其神经保护作用及其分子机制。方法：首先，采用网络药理学方法识别阿普拉米司特和AD之间潜在的共享靶点。随后使用分子对接来评估Apremilast与关键靶点的结合亲和力。在细胞水平上，通过细胞计数试剂盒-8 （CCK-8）检测来评估阿普雷米司特对a β诱导的BV2和HT-22细胞毒性的保护作用。最后，采用Western blot （WB）分析检测PI3K/Akt信号通路中蛋白的表达，从而深入了解Apremilast神经保护作用的分子机制。结果：通过靶富集分析发现了几种潜在通路，我们选择了PI3K/Akt通路进行进一步研究。结果表明，阿普雷米司特能有效抵消a β诱导的BV2和HT-22细胞毒性，显著提高细胞活力。此外，Western blot分析显示磷酸化Akt （p-Akt/Akt）和PI3K蛋白水平上调。结论：本研究提示阿普雷米司特可能通过调节PI3K/Akt信号通路，对a β诱导的BV2和HT-22细胞毒性发挥保护作用。然而，需要进一步验证其剂量和体内疗效。

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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 : 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

Reliable and dynamic monitoring changes in cortical excitation and inhibition balance using aperiodic 1/f slope: functions, diseases and drug effects 利用非周期性1/f斜率可靠和动态监测皮层兴奋和抑制平衡的变化：功能、疾病和药物效应。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-20 DOI: 10.1016/j.neuroscience.2025.12.050

Zeyi Wang , Sungchil Yang , Jianping Lu , Qiang Zhou

Understanding the excitation/inhibition (E/I) balance is fundamental to deciphering cortical circuit dynamics, supporting cognition, and elucidating the pathophysiology of brain disorders, yet methods for assessing E/I balance in vivo remain limited. While recent studies have proposed the aperiodic component (1/f slope) of the local field potentials (LFPs) power spectrum as a potential indicator of E/I balance, this hypothesis has lacked systematic, multi-level in vivo validation. Here, we systematically tested the hypothesis that the aperiodic 1/f slope can serve as a reliable proxy for dynamically monitoring change in E/I balance. In freely moving male mice, we first optimized the analytical parameters for the 1/f slope. We then demonstrated that the slope quantitatively tracks shifts in inhibition induced by pharmacological manipulations in a dose-dependent manner, captures the rapid dynamic shift to inhibition induced by cell-type-specific optogenetic manipulation, and shows generality across drugs altering E/I with diverse mechanisms. On an applied level, we show that the 1/f slope tracks performance-related neural dynamics during a working memory task and indicates the direction of E/I balance in mouse models of epilepsy and depression. Collectively, our findings establish the 1/f slope as a reliable, rapid and sensitive proxy for monitoring E/I balance shift, offering a potential, practical tool for monitoring brain dynamics and as a biomarker for translational research.

了解兴奋/抑制（E/I）平衡是解读皮质电路动力学、支持认知和阐明脑疾病病理生理学的基础，但评估体内E/I平衡的方法仍然有限。虽然最近的研究提出了局部场电位（LFPs）功率谱的非周期分量（1/f斜率）作为E/I平衡的潜在指标，但这一假设缺乏系统的、多层次的体内验证。在这里，我们系统地检验了假设，即非周期性的1/f斜率可以作为动态监测E/I平衡变化的可靠代理。在自由运动的雄性小鼠中，我们首先优化了1/f斜率的分析参数。然后，我们证明了斜率以剂量依赖的方式定量跟踪药理学操作诱导的抑制变化，捕获了细胞类型特异性光遗传学操作诱导的抑制的快速动态变化，并显示了药物以不同机制改变E/I的普遍性。在应用层面上，我们发现1/f斜率跟踪工作记忆任务期间与表现相关的神经动力学，并指示癫痫和抑郁小鼠模型中E/I平衡的方向。总的来说，我们的研究结果确立了1/f斜率作为监测E/I平衡转移的可靠、快速和敏感的代理，为监测脑动力学提供了一个潜在的、实用的工具，并作为转化研究的生物标志物。

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引用次数: 0

Complexity of olfactory-evoked EEG as an evidence-based marker of Alzheimer’s disease 嗅觉诱发脑电图的复杂性作为阿尔茨海默病的循证标志物。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-20 DOI: 10.1016/j.neuroscience.2025.12.049

Justin Joseph , Simi V.R. , Rashmi K.M. , Rashmi R.

Olfactory impairment is an early symptom of Alzheimer’s disease (AD). However, currently used olfactory task-based functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), and electroencephalogram features are not powerful enough to detect the impairment. To address this issue, we propose an explainable Artificial Intelligence (XAI) framework that comprises discriminant analysis/naive Bayes/thresholding classifiers driven by the sample entropy (SE) of olfactory event-related potentials (OERPs) at the Fz/Pz electrodes. The proposed XAI framework exhibits a higher accuracy (92.14%) than methods in the literature, namely, support vector machine (88.20%), logistic regression (67.42%), thresholding (82.5%), and light gradient boosting (80.68%) classifiers fed respectively by inter-electrode β-γ magnitude squared coherence of OERPs, P2 latency of OERPs, fMRI activation pattern of primary olfactory cortex, and NIRS oxygenation difference in the orbito-frontal cortex. Reduction in SE in AD patients is caused by low dynamicity of OERPs as a consequence of diminished sensitivity to the olfactory stimulus.

嗅觉障碍是阿尔茨海默病（AD）的早期症状。然而，目前使用的基于嗅觉任务的功能磁共振成像（fMRI）、功能近红外光谱（fNIRS）和脑电图特征不足以检测到损伤。为了解决这个问题，我们提出了一个可解释的人工智能（XAI）框架，该框架包括由Fz/Pz电极嗅觉事件相关电位（OERPs）的样本熵（SE）驱动的判别分析/朴素贝叶斯/阈值分类器。与支持向量机（88.20%）、逻辑回归（67.42%）、阈值分割（82.5%）和光梯度增强（80.68%）分类器（OERPs的电极间β-γ量级平方一致性、OERPs的P2潜伏期、初级嗅觉皮层的fMRI激活模式和眶额皮质的近红外光谱氧合差异）相比，本文提出的XAI框架具有更高的准确率（92.14%）。AD患者SE的降低是由于对嗅觉刺激的敏感性降低导致OERPs的低活力。

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引用次数: 0

Neuroprotective effects of aegeline against LPS-induced memory dysfunction: involvement of hippocampal cholinergic/proinflammatory cytokines receptor modulation and insilico insight aegeline对lps诱导的记忆功能障碍的神经保护作用：海马胆碱能/促炎细胞因子受体调节和计算机洞察的参与。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-19 DOI: 10.1016/j.neuroscience.2025.12.048

Khalid Saad Alharbi , Sattam Khulaif Alenezi , Tariq G Alsahli , Reem ALQahtani , Muhammad Afzal , Imran Kazmi , Nadeem Sayyed

Aims

This study aimed to evaluate the neuroprotective effects of aegeline on lipopolysaccharide (LPS) −induced cognitive dysfunction in rats.

Background

The global rise in neuroinflammatory and cognitive disorders demands safe and effective plant-based neuroprotective agents. LPS is a potent endotoxin that triggers inflammation and tissue damage. Aegeline, a hydroxyamide derived from Aegle marmelos, exhibits anti-inflammatory and antioxidant properties. However, its ability to modulate hippocampal cholinergic and proinflammatory cytokine receptors, as well as to protect against LPS-induced memory impairment, remains unexplored.

Methods

Aegeline was administered at doses of 5 and 10 mg/kg for seven days to Wistar rats. Behavioral tests included the Y-maze and the Morris water maze (MWM). Biochemical analyses measured acetylcholinesterase (AChE), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), and inflammatory cytokines: tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6. Furthermore, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and caspase-3 markers were evaluated. Additionally, in silico molecular docking and molecular dynamics simulations (MDS) were conducted.

Results

Aegeline treatment improved performance in the Y-maze and MWM tests. It reduced AChE, proinflammatory cytokine, NF-κB, oxidative stress marker, and caspase-3 levels. Antioxidant enzymes and ChAT levels were increased. In silico, aegeline showed strong binding to protein 7JRA with a binding energy of −9.289 kcal/mol, respectively. MDS confirmed the stable interactions with key therapeutic targets.

Conclusion

Aegeline improved cognition, reduced inflammation and oxidative stress, and enhanced antioxidant and cholinergic activity. Its strong molecular binding supports its potential as a neuroprotective agent against memory impairment.

目的：本研究旨在探讨乙酰胆碱对脂多糖（LPS）诱导的大鼠认知功能障碍的神经保护作用。背景：全球神经炎症和认知障碍的增加需要安全有效的植物性神经保护剂。脂多糖是一种强效内毒素，会引发炎症和组织损伤。Aegeline是一种从蜜瓜中提取的羟酰胺，具有抗炎和抗氧化的特性。然而，其调节海马胆碱能和促炎细胞因子受体的能力，以及防止脂多糖引起的记忆障碍的能力，仍未被探索。方法：Wistar大鼠按5、10 mg/kg剂量给药7 d。行为测试包括y形迷宫和Morris水迷宫（MWM）。生化分析检测了乙酰胆碱酯酶（AChE）、胆碱乙酰转移酶（ChAT）、丙二醛（MDA）、谷胱甘肽（GSH）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、一氧化氮（NO）和炎症细胞因子：肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)和IL-6。进一步检测活化B细胞核因子κB轻链增强子（NF-κB）和caspase-3标记物。此外，还进行了分子对接和分子动力学模拟（MDS）。结果：艾格琳治疗改善了y迷宫和MWM测试的表现。降低乙酰胆碱酯酶、促炎细胞因子、NF-κB、氧化应激标志物、caspase-3水平。抗氧化酶和ChAT水平升高。结果表明，egeline与蛋白7JRA结合较强，结合能为-9.289 kcal/mol。MDS证实了与关键治疗靶点的稳定相互作用。结论：Aegeline能改善认知，减轻炎症和氧化应激，增强抗氧化和胆碱能活性。其强大的分子结合能力支持其作为抗记忆障碍的神经保护剂的潜力。

{"title":"Neuroprotective effects of aegeline against LPS-induced memory dysfunction: involvement of hippocampal cholinergic/proinflammatory cytokines receptor modulation and insilico insight","authors":"Khalid Saad Alharbi , Sattam Khulaif Alenezi , Tariq G Alsahli , Reem ALQahtani , Muhammad Afzal , Imran Kazmi , Nadeem Sayyed","doi":"10.1016/j.neuroscience.2025.12.048","DOIUrl":"10.1016/j.neuroscience.2025.12.048","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to evaluate the neuroprotective effects of aegeline on lipopolysaccharide (LPS) −induced cognitive dysfunction in rats.</div></div><div><h3>Background</h3><div>The global rise in neuroinflammatory and cognitive disorders demands safe and effective plant-based neuroprotective agents. LPS is a potent endotoxin that triggers inflammation and tissue damage. Aegeline, a hydroxyamide derived from <em>Aegle marmelos</em>, exhibits anti-inflammatory and antioxidant properties. However, its ability to modulate hippocampal cholinergic and proinflammatory cytokine receptors, as well as to protect against LPS-induced memory impairment, remains unexplored.</div></div><div><h3>Methods</h3><div>Aegeline was administered at doses of 5 and 10 mg/kg for seven days to Wistar rats. Behavioral tests included the Y-maze and the Morris water maze (MWM). Biochemical analyses measured acetylcholinesterase (AChE), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), and inflammatory cytokines: tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6. Furthermore, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and caspase-3 markers were evaluated. Additionally, in silico molecular docking and molecular dynamics simulations (MDS) were conducted.</div></div><div><h3>Results</h3><div>Aegeline treatment improved performance in the Y-maze and MWM tests. It reduced AChE, proinflammatory cytokine, NF-κB, oxidative stress marker, and caspase-3 levels. Antioxidant enzymes and ChAT levels were increased. In silico, aegeline showed strong binding to protein 7JRA with a binding energy of −9.289 kcal/mol, respectively. MDS confirmed the stable interactions with key therapeutic targets.</div></div><div><h3>Conclusion</h3><div>Aegeline improved cognition, reduced inflammation and oxidative stress, and enhanced antioxidant and cholinergic activity. Its strong molecular binding supports its potential as a neuroprotective agent against memory impairment.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 112-129"},"PeriodicalIF":2.8,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harnessing the role of insulin-like growth factor in glioblastoma: a comprehensive review 利用胰岛素样生长因子在胶质母细胞瘤中的作用：综述。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-19 DOI: 10.1016/j.neuroscience.2025.12.044

Ali Nakhaei , Sadaf Afshari , Mohammad Mohammadian , Seyed Sajad Ahmadi , Elmira Mohatshami , Mohammad Jalili-Nik , Mahsa Jalali , Sercan Karav , Amir R. Afshari , Prashant Kesharwani , Amirhossein Sahebkar

This review provides an overview of the biological function of the insulin-like growth factor (IGF) system in glioblastoma (GB) development and a thorough examination of its therapeutic relevance. Networks of microRNAs regulated by insulin-like growth factor 1 (IGF-1) that impede GB’s response to temozolomide (TMZ). The amounts of PDGFR, IGF1R, PI3K, and ERK1/2 proteins and their potential as therapeutic targets. Anti-epidermal growth factor receptor (EGFR) agents may encounter significant resistance from IGF-R inhibitors that operate via PI3K signaling pathways. Insulin-like growth factor-binding protein (IGFBP)-2 modulates CD24, hence increasing the invasiveness of GB cells. 5) Due to the proliferation, invasion, and chemotherapy resistance of GB cells when exposed to exogenous IGFBP-2, targeting the integrin β1/ERK signaling pathway may serve as an effective therapeutic strategy for GB treatment. The IGFBP-2/integrin/ILK/NF-κB network functions as a biologically active signaling pathway in vivo, facilitating the proliferation of GB. Activation of the Hedgehog (HH) pathway and overexpression of the downstream effector GLII accelerate glioma tumorigenicity and the biology of glioma stem cells (GSCs). The aggressive nature of gliomas is attributed to PTEN failure and elevated levels of IGFBP-2 expression. IGFBP-2 augments the expression of CD144 and MMP2, promoting the development of vasculogenic mimicry (VM) in GB cells. Recent investigations have revealed a crucial signaling mechanism that is vital for the survival of GB patients.

本文综述了胰岛素样生长因子（IGF）系统在胶质母细胞瘤（GB）发展中的生物学功能，并对其治疗相关性进行了深入研究。胰岛素样生长因子1 （IGF-1）调控的microrna网络阻碍了GB对替莫唑胺（TMZ）的反应。PDGFR、IGF1R、PI3K和ERK1/2蛋白的数量及其作为治疗靶点的潜力。抗表皮生长因子受体（EGFR）药物可能会遇到通过PI3K信号通路起作用的IGF-R抑制剂的显著耐药性。胰岛素样生长因子结合蛋白(IGFBP)-2调节CD24，从而增加GB细胞的侵袭性。5)由于外源性IGFBP-2对GB细胞的增殖、侵袭和化疗耐药，靶向整合素β1/ERK信号通路可能是GB治疗的有效治疗策略。IGFBP-2/integrin/ILK/NF-κB网络在体内作为具有生物活性的信号通路，促进GB的增殖。Hedgehog （HH）通路的激活和下游效应因子GLII的过度表达加速了胶质瘤的致瘤性和胶质瘤干细胞（GSCs）的生物学特性。胶质瘤的侵袭性是由于PTEN功能衰竭和IGFBP-2表达水平升高。IGFBP-2增加CD144和MMP2的表达，促进GB细胞血管源性模仿（VM）的发展。最近的研究揭示了一个关键的信号机制，对GB患者的生存至关重要。

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引用次数: 0

Developmental consequences of prenatal cannabidiol exposure 产前大麻二酚暴露对发育的影响。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-19 DOI: 10.1016/j.neuroscience.2025.12.051

Tori Humiston, Amanda C. Kentner

引用次数: 0

D-galactose administration via semicircular canal induces accelerated cochlear aging: A novel model of oxidative stress-mediated presbycusis 经半规管给药d -半乳糖诱导耳蜗加速老化：氧化应激介导的老年性耳聋的新模型。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-19 DOI: 10.1016/j.neuroscience.2025.12.052

Chunli Zhao , Zijing Yang , Zhongrui Chen , Ke Liu , Zhengde Du , Shusheng Gong

Age-related hearing loss (ARHL) is a progressive, bilateral sensorineural impairment with significant socio-psychological consequences. Current ARHL models (natural aging or systemic D-galactose (D-gal) injection) face limitations: prolonged timelines, high variability, and inconsistent D-gal protocols. To concentrate aging pathology within the peripheral auditory system, we developed a novel accelerated cochlear aging model by targeted delivery of D-gal via the posterior semicircular canal. This approach aimed to concentrate aging pathology within the peripheral auditory system. Auditory brainstem response testing was employed to assess murine hearing thresholds for determining optimal D-gal concentration and exposure duration. Results demonstrated that by post-administration day 14, the D-gal-H group exhibited pronounced auditory characteristics consistent with ARHL. Morphological staining further revealed significant outer hair cells loss and ribbon synapses degeneration. Concurrently, immunohistochemical analysis of 4-HNE and 8-OHdG showed elevated oxidative stress levels in the stria vascularis, spiral ganglion cells, and inner hair cells of D-gal-treated groups. Substantial alterations in aging-associated proteins were also observed. Mitochondrial membrane potential assessment indicated significant depolarization in treated cochleae. Accordingly, we established a rapid, targeted, and pathologically validated model of cochlear aging, which provides a valuable tool for investigating the mechanisms underlying peripheral auditory aging.

年龄相关性听力损失（ARHL）是一种进行性的双侧感觉神经损伤，具有显著的社会心理后果。目前的ARHL模型（自然老化或全身注射d -半乳糖）面临局限性：时间延长、高可变性和不一致的d -半乳糖方案。为了将衰老病理集中在外周听觉系统，我们通过后半规管靶向递送D-gal建立了一种新的加速耳蜗衰老模型。这种方法的目的是集中老化病理内的外周听觉系统。采用听觉脑干反应测试来评估小鼠的听力阈值，以确定最佳D-gal浓度和暴露时间。结果显示，在给药后第14天，D-gal-H组表现出与ARHL一致的明显听觉特征。形态学染色进一步显示明显的外毛细胞丢失和带状突触变性。同时，免疫组化分析4-HNE和8-OHdG显示d -gal处理组血管纹、螺旋神经节细胞和内毛细胞氧化应激水平升高。衰老相关蛋白也发生了实质性的变化。线粒体膜电位评估显示治疗后耳蜗去极化显著。因此，我们建立了一个快速、有针对性、病理验证的耳蜗老化模型，为研究外周听觉老化机制提供了有价值的工具。

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引用次数: 0

Longitudinal brain-wide recordings reveal early neurophysiological alterations in memory-impaired mice 纵向全脑记录揭示了记忆受损小鼠的早期神经生理改变。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-19 DOI: 10.1016/j.neuroscience.2025.12.035

Abdelrahman B.M. Eldaly , Stephen K. Agadagba , Antara Verma , Kongyan Li , Lee Wei Lim , Leanne Lai-Hang Chan

Scopolamine, a muscarinic receptor antagonist, is widely utilized to pharmacologically model Alzheimer’s disease (AD) due to its ability to mimic cholinergic deficits and induce memory impairments. Despite its common use in investigating behavioral and cognitive impairments in memory deficit animal models, the longitudinal brain-wide electrophysiological alterations associated with scopolamine administration remain largely unexplored. This study integrated electrophysiological and behavioral analyses to investigate scopolamine-induced cognitive deficits in mice. Using a 16-channel intracranial electroencephalography (iEEG) array, we tracked brain-wide oscillatory changes and functional connectivity over 6 weeks during memory task-related and task-free activities. The mouse’s pre-attentive sensory memory was assessed by auditory evoked potentials (AEPs) within the passive oddball mismatch negativity (MMN) paradigm, and the mouse’s spatial working memory was further evaluated using a Y-maze spontaneous alternation task. The auditory MMN responses indicated significant sensory discrimination impairments from Week 2 onward, and spontaneous theta oscillations demonstrated widespread disruptions by Week 3. Concurrently, scopolamine degraded the animal’s Y-maze successful alternation rates. The decline in alternation performance was correlated with the observed electrophysiological alterations, revealing the progressive impact of scopolamine on cognitive and neural functions. Furthermore, this study identified early electrophysiological biomarkers of brain functional network changes associated with memory impairments, in which functional connectivity abnormalities were observed from the first week of scopolamine administration, suggesting they have diagnostic potential in preclinical AD research. By bridging behavioral outcomes with brain-wide iEEG metrics, this work emphasizes the translational relevance of scopolamine models for understanding AD-like pathology and evaluating therapeutic interventions.

东莨菪碱是一种毒蕈碱受体拮抗剂，由于其模仿胆碱能缺陷和诱导记忆障碍的能力，被广泛用于阿尔茨海默病（AD）的药理学模型。尽管它通常用于研究记忆缺陷动物模型中的行为和认知障碍，但与东莨菪碱给药相关的纵向全脑电生理改变在很大程度上仍未被探索。本研究结合电生理和行为分析来研究东莨菪碱引起的小鼠认知缺陷。使用16通道颅内脑电图（iEEG）阵列，我们在6 周内跟踪了与记忆任务相关和无任务活动期间的全脑振荡变化和功能连接。采用听觉诱发电位（AEP）评估小鼠的前注意感觉记忆，并采用y迷宫自发交替任务进一步评估小鼠的空间工作记忆。从第2周开始，听觉MMN反应显示出明显的感觉辨别障碍，自发θ波振荡在第3周显示出广泛的中断。同时，东莨菪碱降低了动物的y迷宫成功交替率。交替表现的下降与观察到的电生理改变相关，揭示了东莨菪碱对认知和神经功能的渐进式影响。此外，本研究确定了与记忆障碍相关的脑功能网络变化的早期电生理生物标志物，其中从东莨菪碱给药的第一周就观察到功能连接异常，这表明它们在临床前AD研究中具有诊断潜力。通过将行为结果与全脑脑电图指标联系起来，本研究强调了东莨菪碱模型在理解ad样病理和评估治疗干预方面的翻译相关性。

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引用次数: 0