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Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles (Microtus ochrogaster) 肢端催产素受体的表达改变了雌性草原田鼠(Microtus ochrogaster)的分子信号传递和社会回避行为
Pub Date : 2024-07-16 DOI: 10.3389/fnins.2024.1409316
Lina K. Nerio-Morales, A. J. Boender, L. J. Young, Marisol R. Lamprea, Adam S. Smith
The social defeat paradigm is the most representative animal model to study social anxiety disorder (SAD) and its underlying neuronal mechanisms. We have previously reported that defeat progressively reduces oxytocin receptors (OXTR) in limbic regions of the brain over an eight-week period in female prairie voles (Microtus ochrogaster). Oxytocin receptors activate the mitogen-activated protein kinase (MAPK) pathway, which has been previously associated with the anxiolytic effects of oxytocin. Here, we assessed the functional significance of OXTR in stress-induced social avoidance and the response of the MAPK signaling pathway in the nucleus accumbens (NAc), anterior cingulate cortex (ACC), and basolateral amygdala (BLA) of female prairie voles.In experiment 1, Sexually naïve adult female prairie voles were defeated for three consecutive days and tested a week after for social preference/avoidance (SPA) test. Control subjects were similarly handled without defeat conditioning. In experiment 2, sexually and stress naïve adult female prairie voles were bilaterally injected into the NAc, ACC, or the BLA with a CRISPR/Cas9 virus targeting the Oxtr coding sequence to induce OXTR knockdown. Two weeks post-surgery, subjects were tested for SPA behavior. Viral control groups were similarly handled but injected with a control virus. A subgroup of animals from each condition in both experiments were similarly treated and euthanized without being tested for SPA behavior. Brains were harvested for OXTR autoradiography, western blot analysis of MAPK proteins and quantification of local oxytocin content in the NAc, BLA, ACC, and PVN through ELISA.Social defeat reduced OXTR binding in the NAc and affected MAPK pathway activity and oxytocin availability. These results were region-specific and sensitive to exposure to the SPA test. Additionally, OXTR knockdown in the NAc, ACC, and BLA induced social avoidance and decreased basal MAPK activity in the NAc. Finally, we found that OXTR knockdown in these regions was associated with less availability of oxytocin in the PVN.Dysregulation of the oxytocin system and MAPK signaling pathway in the NAc, ACC, and BLA are important in social behavior disruptions in female voles. This dysregulation could, therefore, play an important role in the etiology of SAD in women.
社交失败范例是研究社交焦虑症(SAD)及其潜在神经元机制的最具代表性的动物模型。我们以前曾报道过,在为期八周的时间里,失败会逐渐减少雌性草原田鼠(Microtus ochrogaster)大脑边缘区域的催产素受体(OXTR)。催产素受体会激活丝裂原活化蛋白激酶(MAPK)通路,这与催产素的抗焦虑作用有关。在实验1中,我们评估了催产素受体在应激诱导的社交回避中的功能意义,以及MAPK信号通路在雌性草原田鼠的伏隔核(NAc)、前扣带回皮层(ACC)和基底外侧杏仁核(BLA)中的反应。对照组受试者的处理方法与此类似,但未进行失败条件反射。在实验 2 中,向性和应激均未受影响的成年雌性草原田鼠的 NAc、ACC 或 BLA 双侧注射靶向 Oxtr 编码序列的 CRISPR/Cas9 病毒,以诱导 OXTR 基因敲除。手术后两周,受试者接受 SPA 行为测试。病毒对照组的处理方法类似,但注射的是对照病毒。两项实验中每种情况下都有一个动物子组接受了类似的处理,并在未进行 SPA 行为测试的情况下安乐死。采集大脑进行 OXTR 自显影、MAPK 蛋白 Western 印迹分析,并通过 ELISA 对 NAc、BLA、ACC 和 PVN 中的催产素含量进行定量。这些结果具有区域特异性,并且对暴露于SPA测试很敏感。此外,在NAc、ACC和BLA中敲除OXTR会诱发社交回避,并降低NAc中MAPK的基础活性。最后,我们发现这些区域的 OXTR 基因敲除与 PVN 中催产素的可用性降低有关。因此,这种失调可能在女性 SAD 的病因中扮演重要角色。
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引用次数: 0
Systems genetics identifies methionine as a high risk factor for Alzheimer's disease 系统遗传学确定蛋氨酸是阿尔茨海默病的高危因素
Pub Date : 2024-07-16 DOI: 10.3389/fnins.2024.1381889
Congmin Wang, Yu Hei, Yu Liu, A. Bajpai, Yuhe Li, Yawen Guan, Fuyi Xu, Cuifang Yao
As a dietary strategy, methionine restriction has been reported to promote longevity and regulate metabolic disorders. However, the role and possible regulatory mechanisms underlying methionine in neurodegenerative diseases such as Alzheimer's disease (AD), remain unexplored. This study utilized the data from BXD recombinant inbred (RI) mice to establish a correlation between the AD phenotype in mice and methionine level. Gene enrichment analysis indicated that the genes associated with the concentration of methionine in the midbrain are involved in the dopaminergic synaptic signaling pathway. Protein interaction network analysis revealed that glycogen synthase kinase 3 beta (GSK-3β) was a key regulator of the dopaminergic synaptic pathway and its expression level was significantly correlated with the AD phenotype. Finally, in vitro experiments demonstrated that methionine deprivation could reduce the expression of Aβ and phosphorylated Tau, suggesting that lowering methionine levels in humans may be a preventive or therapeutic strategy for AD. In conclusion, our findings support that methionine is a high risk factor for AD. These findings predict potential regulatory network, theoretically supporting methionine restriction to prevent AD.
据报道,作为一种饮食策略,限制蛋氨酸摄入可促进长寿和调节代谢紊乱。然而,蛋氨酸在阿尔茨海默病(AD)等神经退行性疾病中的作用和可能的调节机制仍有待探索。本研究利用 BXD 重组近交系(RI)小鼠的数据,建立了小鼠 AD 表型与蛋氨酸水平之间的相关性。基因富集分析表明,与中脑蛋氨酸浓度相关的基因参与了多巴胺能突触信号通路。蛋白质相互作用网络分析显示,糖原合成酶激酶3β(GSK-3β)是多巴胺能突触通路的关键调控因子,其表达水平与AD表型显著相关。最后,体外实验表明,剥夺蛋氨酸可减少Aβ和磷酸化Tau的表达,这表明降低人体蛋氨酸水平可能是一种预防或治疗AD的策略。总之,我们的研究结果支持蛋氨酸是AD的高危因素。这些发现预测了潜在的调控网络,从理论上支持限制蛋氨酸来预防AD。
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引用次数: 0
Editorial: Development of circadian clock functions, volume II 社论:昼夜节律时钟功能的发展,第 II 卷
Pub Date : 2024-07-16 DOI: 10.3389/fnins.2024.1453328
Jihwan Myung, Rae Silver, Jeff R. Jones, Takahiro J. Nakamura, Daisuke Ono
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引用次数: 0
Alpha and theta oscillations on a visual strategic processing task in age-related hearing loss 老年性听力损失患者在视觉策略处理任务中的α和θ振荡
Pub Date : 2024-07-16 DOI: 10.3389/fnins.2024.1382613
Shraddha A. Shende, Sarah E. Jones, R. Mudar
Emerging evidence suggests changes in several cognitive control processes in individuals with age-related hearing loss (ARHL). However, value-directed strategic processing, which involves selectively processing salient information based on high value, has been relatively unexplored in ARHL. Our previous work has shown behavioral changes in strategic processing in individuals with ARHL. The current study examined event-related alpha and theta oscillations linked to a visual, value-directed strategic processing task in 19 individuals with mild untreated ARHL and 17 normal hearing controls of comparable age and education.Five unique word lists were presented where words were assigned high- or low-value based on the letter case, and electroencephalography (EEG) data was recorded during task performance.The main effect of the group was observed in early time periods. Specifically, greater theta synchronization was seen in the ARHL group relative to the control group. Interaction between group and value was observed at later time points, with greater theta synchronization for high- versus low-value information in those with ARHL.Our findings provide evidence for oscillatory changes tied to a visual task of value-directed strategic processing in individuals with mild untreated ARHL. This points towards modality-independent neurophysiological changes in cognitive control in individuals with mild degrees of ARHL and adds to the rapidly growing literature on the cognitive consequences of ARHL.
新的证据表明,老年性听力损失(ARHL)患者的几个认知控制过程发生了变化。然而,价值导向的策略处理,即根据高价值选择性地处理突出信息,在 ARHL 患者中还相对缺乏研究。我们之前的研究表明,ARHL 患者的策略处理行为发生了变化。本研究检测了 19 名未经治疗的轻度 ARHL 患者和 17 名年龄和教育程度相当的听力正常对照组患者与视觉、价值导向的策略处理任务相关的事件相关α和θ振荡。具体来说,与对照组相比,ARHL 组的θ 同步性更高。我们的研究结果提供了证据,证明轻度未经治疗的 ARHL 患者的振荡变化与以价值为导向的策略处理视觉任务有关。这表明轻度 ARHL 患者的认知控制发生了与模式无关的神经生理学变化,为有关 ARHL 认知后果的快速增长的文献增添了新的内容。
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引用次数: 0
DFA-UNet: dual-stream feature-fusion attention U-Net for lymph node segmentation in lung cancer diagnosis DFA-UNet:用于肺癌诊断中淋巴结分割的双流特征融合注意 U-Net
Pub Date : 2024-07-15 DOI: 10.3389/fnins.2024.1448294
Qi Zhou, Yingwen Zhou, Nailong Hou, Yaxuan Zhang, Guanyu Zhu, Liang Li
In bronchial ultrasound elastography, accurately segmenting mediastinal lymph nodes is of great significance for diagnosing whether lung cancer has metastasized. However, due to the ill-defined margin of ultrasound images and the complexity of lymph node structure, accurate segmentation of fine contours is still challenging. Therefore, we propose a dual-stream feature-fusion attention U-Net (DFA-UNet). Firstly, a dual-stream encoder (DSE) is designed by combining ConvNext with a lightweight vision transformer (ViT) to extract the local information and global information of images; Secondly, we propose a hybrid attention module (HAM) at the bottleneck, which incorporates spatial and channel attention to optimize the features transmission process by optimizing high-dimensional features at the bottom of the network. Finally, the feature-enhanced residual decoder (FRD) is developed to improve the fusion of features obtained from the encoder and decoder, ensuring a more comprehensive integration. Extensive experiments on the ultrasound elasticity image dataset show the superiority of our DFA-UNet over 9 state-of-the-art image segmentation models. Additionally, visual analysis, ablation studies, and generalization assessments highlight the significant enhancement effects of DFA-UNet. Comprehensive experiments confirm the excellent segmentation effectiveness of the DFA-UNet combined attention mechanism for ultrasound images, underscoring its important significance for future research on medical images.
在支气管超声弹性成像中,准确分割纵隔淋巴结对诊断肺癌是否转移意义重大。然而,由于超声图像边缘不清晰,淋巴结结构复杂,准确分割精细轮廓仍具有挑战性。因此,我们提出了一种双流特征融合注意力 U-Net (DFA-UNet)。首先,结合 ConvNext 和轻量级视觉变换器(ViT)设计了双流编码器(DSE),以提取图像的局部信息和全局信息;其次,我们在瓶颈处提出了混合注意力模块(HAM),它结合了空间注意力和通道注意力,通过优化网络底部的高维特征来优化特征传输过程。最后,开发了特征增强残差解码器(FRD),以改进编码器和解码器所获特征的融合,确保更全面的整合。在超声弹性图像数据集上的广泛实验表明,我们的 DFA-UNet 优于 9 种最先进的图像分割模型。此外,视觉分析、消融研究和泛化评估也凸显了 DFA-UNet 的显著增强效果。综合实验证实了 DFA-UNet 联合注意力机制在超声波图像中的出色分割效果,突出了它对未来医学图像研究的重要意义。
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引用次数: 0
Blocking Aδ- and C-fiber neural transmission by sub-kilohertz peripheral nerve stimulation 通过亚千赫外周神经刺激阻断 Aδ 和 C 纤维神经传递
Pub Date : 2024-07-15 DOI: 10.3389/fnins.2024.1404903
Shaopeng Zhang, Longtu Chen, Sajjad Rigi Ladez, Ahmet Seferge, Jia Liu, Bin Feng
We recently showed that sub-kilohertz electrical stimulation of the afferent somata in the dorsal root ganglia (DRG) reversibly blocks afferent transmission. Here, we further investigated whether similar conduction block can be achieved by stimulating the nerve trunk with electrical peripheral nerve stimulation (ePNS).We explored the mechanisms and parameters of conduction block by ePNS via ex vivo single-fiber recordings from two somatic (sciatic and saphenous) and one autonomic (vagal) nerves harvested from mice. Action potentials were evoked on one end of the nerve and recorded on the other end from teased nerve filaments, i.e., single-fiber recordings. ePNS was delivered in the middle of the nerve trunk using a glass suction electrode at frequencies of 5, 10, 50, 100, 500, and 1000 Hz.Suprathreshold ePNS reversibly blocks axonal neural transmission of both thinly myelinated Aδ-fiber axons and unmyelinated C-fiber axons. ePNS leads to a progressive decrease in conduction velocity (CV) until transmission blockage, suggesting activity-dependent conduction slowing. The blocking efficiency is dependent on the axonal conduction velocity, with Aδ-fibers efficiently blocked by 50–1000 Hz stimulation and C-fibers blocked by 10–50 Hz. The corresponding NEURON simulation of action potential transmission indicates that the disrupted transmembrane sodium and potassium concentration gradients underly the transmission block by the ePNS.The current study provides direct evidence of reversible Aδ- and C-fiber transmission blockage by low-frequency (<100 Hz) electrical stimulation of the nerve trunk, a previously overlooked mechanism that can be harnessed to enhance the therapeutic effect of ePNS in treating neurological disorders.
我们最近发现,对背根神经节(DRG)传入体的亚千赫电刺激可逆性地阻断传入传导。在此,我们进一步研究了通过外周神经电刺激(ePNS)刺激神经干是否能实现类似的传导阻滞。我们通过从小鼠身上采集的两条躯体神经(坐骨神经和隐神经)和一条自主神经(迷走神经)的体外单纤维记录,探索了 ePNS 传导阻滞的机制和参数。在神经的一端诱发动作电位,在另一端通过挑逗神经丝记录动作电位,即单纤记录、阈上 ePNS 可逆性地阻断髓鞘较薄的 Aδ 纤维轴突和无髓鞘的 C 纤维轴突的轴突神经传导。阻断效率取决于轴突传导速度,50-1000 赫兹的刺激可有效阻断 Aδ 纤维,10-50 赫兹的刺激可阻断 C 纤维。目前的研究提供了低频(<100 Hz)电刺激神经干可逆性阻断 Aδ 和 C 纤维传导的直接证据,这是一种以前被忽视的机制,可以利用它来增强 ePNS 在治疗神经系统疾病方面的疗效。
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引用次数: 0
On the performance of seizure prediction machine learning methods across different databases: the sample and alarm-based perspectives 不同数据库中癫痫发作预测机器学习方法的性能:基于样本和警报的视角
Pub Date : 2024-07-15 DOI: 10.3389/fnins.2024.1417748
Inês Andrade, César Teixeira, Mauro F. Pinto
Epilepsy affects 1% of the global population, with approximately one-third of patients resistant to anti-seizure medications (ASMs), posing risks of physical injuries and psychological issues. Seizure prediction algorithms aim to enhance the quality of life for these individuals by providing timely alerts. This study presents a patient-specific seizure prediction algorithm applied to diverse databases (EPILEPSIAE, CHB-MIT, AES, and Epilepsy Ecosystem). The proposed algorithm undergoes a standardized framework, including data preprocessing, feature extraction, training, testing, and postprocessing. Various databases necessitate adaptations in the algorithm, considering differences in data availability and characteristics. The algorithm exhibited variable performance across databases, taking into account sensitivity, FPR/h, specificity, and AUC score. This study distinguishes between sample-based approaches, which often yield better results by disregarding the temporal aspect of seizures, and alarm-based approaches, which aim to simulate real-life conditions but produce less favorable outcomes. Statistical assessment reveals challenges in surpassing chance levels, emphasizing the rarity of seizure events. Comparative analyses with existing studies highlight the complexity of standardized assessments, given diverse methodologies and dataset variations. Rigorous methodologies aiming to simulate real-life conditions produce less favorable outcomes, emphasizing the importance of realistic assumptions and comprehensive, long-term, and systematically structured datasets for future research.
癫痫影响着全球1%的人口,其中约三分之一的患者对抗癫痫药物(ASMs)产生抗药性,带来身体伤害和心理问题的风险。癫痫发作预测算法旨在通过提供及时警报来提高这些患者的生活质量。本研究介绍了一种适用于不同数据库(EPILEPSIAE、CHB-MIT、AES 和癫痫生态系统)的患者特定癫痫发作预测算法。该算法采用标准化框架,包括数据预处理、特征提取、训练、测试和后处理。考虑到数据可用性和特征的差异,不同的数据库需要对算法进行调整。考虑到灵敏度、FPR/h、特异性和 AUC 分数,该算法在不同数据库中表现出不同的性能。本研究对基于样本的方法和基于警报的方法进行了区分,前者通常通过忽略癫痫发作的时间性而获得更好的结果,后者旨在模拟现实生活中的情况,但产生的结果较差。统计评估揭示了超越偶然水平的挑战,强调了癫痫发作事件的罕见性。与现有研究的对比分析凸显了标准化评估的复杂性,因为方法和数据集各不相同。旨在模拟真实情况的严格方法产生的结果并不理想,这强调了现实假设以及全面、长期和系统化的数据集对未来研究的重要性。
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引用次数: 0
Editorial: Information theory meets deep neural networks: theory and applications 社论:信息论与深度神经网络:理论与应用
Pub Date : 2024-07-15 DOI: 10.3389/fnins.2024.1448517
Anguo Zhang, Qichun Zhang, Kai Zhao
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引用次数: 0
Editorial: Brain abnormalities due to genetic alterations or developmental exposure to environmental factors, volume II 社论:遗传改变或发育过程中暴露于环境因素导致的大脑异常,第 II 卷
Pub Date : 2024-07-11 DOI: 10.3389/fnins.2024.1389145
Kazuhiko Sawada, Atsushi Yoshiki, Shigeyoshi Saito
{"title":"Editorial: Brain abnormalities due to genetic alterations or developmental exposure to environmental factors, volume II","authors":"Kazuhiko Sawada, Atsushi Yoshiki, Shigeyoshi Saito","doi":"10.3389/fnins.2024.1389145","DOIUrl":"https://doi.org/10.3389/fnins.2024.1389145","url":null,"abstract":"","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":"95 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141657989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial: Current therapeutic approaches in Alzheimer's disease: the use of a second drug with anti-amyloid-beta and beyond 社论:当前阿尔茨海默病的治疗方法:使用第二种抗淀粉样蛋白-β药物及其他药物
Pub Date : 2024-07-08 DOI: 10.3389/fnins.2024.1449365
Joon W. Shim, Hyacinth I. Hyacinth, Oscar Gonzalez-Perez
{"title":"Editorial: Current therapeutic approaches in Alzheimer's disease: the use of a second drug with anti-amyloid-beta and beyond","authors":"Joon W. Shim, Hyacinth I. Hyacinth, Oscar Gonzalez-Perez","doi":"10.3389/fnins.2024.1449365","DOIUrl":"https://doi.org/10.3389/fnins.2024.1449365","url":null,"abstract":"","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":"7 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141667955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Frontiers in Neuroscience
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