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Anesthetic-like effects of ketamine in C. elegans 氯胺酮对优雅类动物的麻醉效应
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-17 DOI: 10.1016/j.neuroscience.2024.11.042
Katariina Seppälä , Inés Reigada , Olli Matilainen , Tomi Rantamäki , Leena Hanski
Transparency of Caenorhabditis elegans enables microscopic in vivo imaging of cellular processes, but immobilization is required due to high locomotor activity. Here, anesthetic-like effects of dissociate anesthetic ketamine in adult C. elegans are presented using video recordings and infrared-based automated activity tracking. Ketamine caused a reversible blockade of locomotion at a similar concentration (20–50 mM) at which conventionally used immobilizing agent sodium azide (NaN3) produces paralysis. The levels of immobilization at 20 mM ketamine enabled fluorescent and brightfield imaging. The worms’ locomotory activity recovered fully after ketamine exposure and no acute toxicity was observed. However, a marked chemosensation deficiency was noted immediately after 20 mM ketamine exposure. Short-term ketamine treatment did not show signs of SKN-1 (skinhead-1) activation, a marker of the stress response associated with NaN3. In sum, our results show ketamine’s potential as a non-toxic nematode immobilizing agent and rationalize C. elegans as a model organism to understand its pharmacology.
线虫的透明性使其能够在显微镜下对细胞过程进行活体成像,但由于其运动活动频繁,因此需要将其固定。在此,我们利用视频记录和基于红外线的自动活动追踪技术介绍了氯胺酮对成年眼镜蛇的类似麻醉作用。氯胺酮可在类似于传统固定剂叠氮化钠(NaN3)产生麻痹的浓度(20-50 mM)下导致可逆的运动阻滞。在 20 mM 氯胺酮的固定水平下,可以进行荧光和明视野成像。暴露于氯胺酮后,蠕虫的运动活性完全恢复,而且没有观察到急性毒性。然而,暴露于20毫摩尔氯胺酮后立即出现了明显的化学感觉缺陷。氯胺酮的短期处理并未显示出 SKN-1(skinhead-1)激活的迹象,而 SKN-1 是与 NaN3 相关的应激反应的标志物。总之,我们的研究结果表明氯胺酮具有作为一种无毒线虫固定剂的潜力,并合理地将秀丽隐杆线虫作为了解其药理学的模式生物。
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引用次数: 0
Advances in diagnostic imaging and interventional treatment of aphasia after basal ganglia stroke 基底节中风后失语症的影像诊断和介入治疗进展。
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-16 DOI: 10.1016/j.neuroscience.2024.11.035
Xinyue-Cheng , Wenjing-Gu , Xuewei-Li , Yuchen Liang , Dehong-Liu , Hongwei-Zhou
Post-stroke basal ganglia aphasia is an unusual and transient form of aphasia resulting from basal ganglia damage. It is commonly believed that the generation of language function primarily resides in regular language regions of the brain; however, recent findings indicate a prevalence of basal ganglia stroke aphasia as high as 22%. Subcortical structures (e.g., basal ganglia) also play an important role in language processing. Aphasia seriously affects the quality of life and functional outcomes of patients, and early diagnosis and intervention are important for the prognosis of and rehabilitation from aphasia after basal ganglia stroke. In recent years, the main diagnostic methods for basal ganglia aphasia include diffusion tensor imaging, diffusion spectral imaging, and functional magnetic resonance imaging, which explore the changes in patients with basal ganglia aphasia compared to those without from the perspectives of fiber tract imaging and brain function alteration, respectively, and are able to predict the recovery of patients before and after treatment. Treatment for post-stroke basal ganglia aphasia includes transcranial magnetic stimulation, a recent emerging therapeutic technique, in addition to conventional medications and speech rehabilitation. Consequently, understanding this condition is crucial. This review delves into its causes, imaging methods, and therapeutic interventions, offering a systematic and comprehensive analysis of these aspects.
中风后基底节失语症是因基底节受损而导致的一种不常见的短暂性失语症。一般认为,语言功能的产生主要在大脑的常规语言区域;然而,最近的研究结果表明,基底节卒中失语症的发病率高达 22%。皮层下结构(如基底节)在语言处理过程中也发挥着重要作用。失语严重影响患者的生活质量和功能预后,早期诊断和干预对基底节卒中失语的预后和康复非常重要。近年来,基底节失语症的主要诊断方法包括弥散张量成像、弥散频谱成像和功能磁共振成像,分别从纤维束成像和脑功能改变的角度探讨基底节失语症患者与非基底节失语症患者的变化,能够预测患者治疗前后的恢复情况。脑卒中后基底节失语症的治疗除了传统的药物治疗和语言康复外,还包括经颅磁刺激这一近年来新兴的治疗技术。因此,了解这一病症至关重要。本综述深入探讨了其病因、成像方法和治疗干预措施,对这些方面进行了系统而全面的分析。
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引用次数: 0
How the brain differentiates human and monkey faces: Neuromagnetic evidence from spatiotemporal dynamics. 大脑如何区分人脸和猴脸:来自时空动态的神经磁性证据
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-16 DOI: 10.1016/j.neuroscience.2024.11.018
Emi Yamada, Akinori Takeda, Hisato Nakazono, Mutsuhide Tanaka, Katsuya Ogata, Shozo Tobimatsu

Face recognition is an important aspect of human non-verbal communication. Event-related potentials or magnetic fields, such as the N170/M170 component, are considered essential neural markers of face processing. Compared to upright human faces, inverted human faces and upright but not inverted animal faces cause longer latencies and larger amplitudes of these components. However, the mechanisms underlying this factor remain unclear. To elucidate the spatiotemporal dynamics of the processing of inverted human and animal faces, we recorded face-selective responses (M170) to upright and inverted human and monkey faces using a 306-channel whole-head magnetoencephalography. Sensor analysis showed an increased M170 latency and amplitude for inverted human and upright animal faces. However, in the source analysis, the observed modulations of the estimated spatiotemporal dynamics were different from the sensor results: irrespective of species, upright faces activated wider areas in the ventral and dorsal visual regions compared with inverted faces. Additionally, face orientation differentially modulated the anterior region of the fusiform gyrus (FG) in both face categories. These results suggest that spatiotemporal dynamics differ in face orientation regardless of category and that the FG contributes little or nothing to the M170 modulation recorded in the scalp sensor. Furthermore, we demonstrated that inverted human and animal faces are processed via different mechanisms.

人脸识别是人类非语言交流的一个重要方面。事件相关电位或磁场(如 N170/M170 分量)被认为是人脸处理过程中的重要神经标记。与直立的人脸相比,倒立的人脸和直立而非倒立的动物脸会导致这些成分的潜伏期更长、振幅更大。然而,这一因素的内在机制仍不清楚。为了阐明倒置人脸和动物脸的时空动态处理,我们使用 306 通道全头脑磁图记录了对直立和倒置人脸和猴脸的脸选择性反应(M170)。传感器分析表明,倒置的人脸和直立的动物脸的 M170 潜伏期和振幅都有所增加。然而,在源分析中,所观察到的估计时空动态的调节与传感器的结果不同:与倒立的人脸相比,无论哪种动物,直立的人脸都会激活腹侧和背侧视觉区域中更宽的区域。此外,在两种面孔类别中,面孔方位对纺锤形回(FG)前部区域的调节也不同。这些结果表明,无论面孔类别如何,面孔方位的时空动态都是不同的,而 FG 对头皮传感器记录到的 M170 调制几乎没有贡献。此外,我们还证明了倒置的人脸和动物脸通过不同的机制进行处理。
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引用次数: 0
Sleep deprivation impairs spatial cognitive processing and Alters brain connectivity in table tennis athletes 睡眠不足会损害乒乓球运动员的空间认知处理能力并改变大脑连通性
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-16 DOI: 10.1016/j.neuroscience.2024.11.039
Ziyi Peng , Zexuan Wang , Lin Xu , Yongcong Shao , Fubing Jiao , Jing Lv
Spatial cognitive ability is critical for table tennis athletes to achieve excellent competitive performance, and sleep may be an important factor influencing this ability. This study investigated the impact of 36h sleep deprivation on the spatial cognitive processing of 20 s-level table tennis athletes, using event-related potentials and functional connectivity analysis to assess changes in cognitive resource allocation and inter-regional brain coordination before and after sleep deprivation. The results showed that sleep deprivation significantly prolonged reaction time and led to a decrease in P3 amplitude, reflecting a reduction in participants’ attentional resource allocation and cognitive processing capacity. Functional connectivity analysis further revealed that β frequency band functional connectivity between the frontal and occipital regions significantly decreased after sleep deprivation, indicating reduced brain efficiency in processing spatial information. After 36 h of SD, the spatial cognitive ability of table tennis athletes was impaired. SD not only led to a reduction in the allocation of attentional resources and cognitive processing capabilities in these athletes, but also weakened functional connectivity between the frontal and occipital lobes of the brain.
空间认知能力是乒乓球运动员取得优异竞技成绩的关键,而睡眠可能是影响这一能力的重要因素。本研究采用事件相关电位和功能连接分析法评估了睡眠剥夺前后认知资源分配和大脑区域间协调的变化,研究了剥夺36小时睡眠对20名s级乒乓球运动员空间认知处理能力的影响。结果显示,睡眠剥夺明显延长了反应时间,并导致P3振幅下降,反映出参与者的注意资源分配和认知处理能力下降。功能连接分析进一步显示,睡眠剥夺后额叶区和枕叶区之间的β频带功能连接明显降低,表明大脑处理空间信息的效率降低。睡眠不足36小时后,乒乓球运动员的空间认知能力受损。自毁睡眠不仅导致这些运动员的注意资源分配和认知处理能力下降,还削弱了大脑额叶和枕叶之间的功能连接。
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引用次数: 0
Astrocytic calcium signals modulate exercise-induced fatigue in mice. 星形胶质细胞钙信号调节小鼠运动引起的疲劳
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-15 DOI: 10.1016/j.neuroscience.2024.11.033
Liyang Xiang, Yulu Zhao, XinRui Li, Ran Shi, Zhou Wen, Xiaohang Xu, Yifan Hu, Qianyun Xu, Yaodan Chen, Jin Ma, Weida Shen

Exercise-induced fatigue (EF) is characterized by a decline in maximal voluntary muscle force following prolonged physical activity, influenced by both peripheral and central factors. Central fatigue involves complex interactions within the central nervous system (CNS), where astrocytes play a crucial role. This study explores the impact of astrocytic calcium signals on EF. We used adeno-associated viruses to express GCaMP7b in astrocytes of the dorsal striatum in mice, allowing us to monitor calcium dynamics. Our findings reveal that EF significantly increases the frequency of spontaneous astrocytic calcium signals. Utilizing genetic tools to either enhance or reduce astrocytic calcium signaling, we observed corresponding decreases and increases in exercise-induced fatigue time, respectively. Furthermore, modulation of astrocytic calcium signals influenced corticostriatal synaptic plasticity, with increased signals impairing and decreased signals ameliorating long-term depression (LTD). These results highlight the pivotal role of astrocytic calcium signaling in the regulation of exercise-induced fatigue and synaptic plasticity in the striatum.

运动诱发疲劳(EF)的特征是在长时间体力活动后最大自主肌力下降,这同时受到外周和中枢因素的影响。中枢疲劳涉及中枢神经系统(CNS)内复杂的相互作用,其中星形胶质细胞起着至关重要的作用。本研究探讨了星形胶质细胞钙信号对 EF 的影响。我们利用腺相关病毒在小鼠背侧纹状体的星形胶质细胞中表达 GCaMP7b,从而监测钙离子的动态变化。我们的研究结果表明,EF 能显著增加星形胶质细胞自发钙信号的频率。利用基因工具增强或减少星形胶质细胞的钙信号,我们观察到运动诱导的疲劳时间分别相应减少和增加。此外,星形胶质细胞钙信号的调节还影响了皮层突触的可塑性,信号增强会损害长期抑制(LTD),信号减弱则会改善长期抑制(LTD)。这些结果凸显了星形胶质细胞钙信号在调节运动引起的疲劳和纹状体突触可塑性中的关键作用。
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引用次数: 0
Atypical brain network topology of the triple network and cortico-subcortical network in autism spectrum disorder 自闭症谱系障碍中三重网络和皮质-皮质下网络的非典型脑网络拓扑结构。
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-15 DOI: 10.1016/j.neuroscience.2024.11.034
Jun-Sa Zhu , Qi Gong , Mei-Ting Zhao , Yun Jiao
The default mode network (DMN), salience network (SN), and central executive control network (CEN) form the well-known triple network, providing a framework for understanding various neurodevelopmental and psychiatric disorders. However, the topology of this network remains unclear in autism spectrum disorder (ASD). To gain a more profound understanding of ASD, we explored the topology of the triple network in ASD. Additionally, the striatum and thalamus are pivotal centres of information transmission within the brain, and the realization of various brain functions requires the coordination of cortical and subcortical structures. Therefore, we also investigated the topology of the cortico-subcortical network in ASD, which consists of the DMN, SN, CEN, striatum, and thalamus. Resting-state functional magnetic resonance imaging data on 208 ASD patients and 278 typically developing (TD) controls (8–18 years old) were obtained from the Autism Brain Imaging Data Exchange database. We performed graph theory analysis on the triple network and the cortico-subcortical network. The results showed that the triple network’s clustering coefficient, lambda, and network local efficiency values were significantly lower in ASD, and the nodal degree and efficiency of the medial prefrontal cortex also decreased. For the cortico-subcortical network, the sigma, clustering coefficient, gamma, and network local efficiency showed the same reduction, and the altered clustering coefficient negatively correlated with ASD manifestations. In addition, the interaction between the DMN and CEN was more robust in ASD patients. These findings enhance our understanding of ASD and suggest that subcortical structures should be more considered in future ASD related studies.
默认模式网络(DMN)、显著性网络(SN)和中央执行控制网络(CEN)构成了众所周知的三重网络,为理解各种神经发育和精神疾病提供了框架。然而,自闭症谱系障碍(ASD)中这一网络的拓扑结构仍不清楚。为了更深入地了解自闭症谱系障碍,我们探索了自闭症谱系障碍中三重网络的拓扑结构。此外,纹状体和丘脑是脑内信息传递的关键中心,各种脑功能的实现需要皮层和皮层下结构的协调。因此,我们还研究了ASD患者皮质-皮质下网络的拓扑结构,该网络由DMN、SN、CEN、纹状体和丘脑组成。我们从自闭症脑成像数据交换数据库中获得了208名ASD患者和278名发育典型(TD)对照组(8-18岁)的静息态功能磁共振成像数据。我们对三重网络和皮质-皮质下网络进行了图论分析。结果显示,三重网络的聚类系数、λ和网络局部效率值在自闭症患者中明显降低,内侧前额叶皮层的节点度和效率也有所下降。皮质-皮质下网络的σ、聚类系数、γ和网络局部效率也出现了同样的降低,聚类系数的改变与ASD表现呈负相关。此外,在ASD患者中,DMN与CEN之间的相互作用更为强大。这些发现加深了我们对ASD的理解,并表明在未来的ASD相关研究中应更多地考虑皮层下结构。
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引用次数: 0
Cerebral microbleeds linked to structural network disruption and cognitive impairment in white matter hyperintensities 脑微出血与白质高密度症的结构网络破坏和认知障碍有关。
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-15 DOI: 10.1016/j.neuroscience.2024.11.027
Jiabin Yin , Xia Zhou , Yali Chen , Yue Sun , Chaojuan Huang , Yating Tang , Wenhao Zhu , Xiaoqun Zhu , Zhongwu Sun

Objective

This study aims to explore the relationship between the cerebral microbleeds (CMBs) and white matter structural network in patients with white matter hyperintensities (WMHs), and the correlation with the cognitive impairment.

Method

One hundred and fifty-eight participants with WMHs underwent 3.0 T magnetic resonance imaging scans and neuropsychological assessment. The grouping method included count grading with categories: non-CMBs (n-CMBs), CMBs < 5, and CMBs ≥ 5. Additionally, the distribution of CMBs was considered, distinguishing between strictly lobar CMBs (SL-CMBs) and deep or infratentorial CMBs (DI-CMBs). Diffusion tensor imaging was employed to construct the white matter structural network for each participant. Subsequently, we analyzed the correlations between the topological parameters of network and cognitive performance in individuals with CMBs.

Results

Compared with n-CMBs group, both CMBs ≥ 5 and DI-CMBs participants exhibited a significant decreased in global efficiency and increased in characteristic path length. Moreover, in the nodal network metrics, the CMBs ≥ 5 showed the left middle occipital gyrus (MOG.L) of nodal efficiency and nodal shortest path correlated with SCWT-A and MMSE, while in the DI-CMBs groups, the left cuneus (CUN.L) of nodal shortest path correlated with SCWT-A. However, there were no significant neuropsychological correlations observed in the SL-CMBs and CMBs < 5 groups.

Conclusion

In this study, patients with a high count (≥5) of CMBs or DI-CMBs are associated with disruptions in the microstructure of the white matter structural network, partially impacting the visual network of occipital lobe and affecting the cognitive function of information processing speed and attention.
研究目的本研究旨在探讨白质高密度症(WMHs)患者的脑微小出血(CMBs)与白质结构网络之间的关系,以及与认知障碍的相关性:158名WMHs患者接受了3.0 T磁共振成像扫描和神经心理学评估。分组方法包括计数分级:非 CMBs 组(n-CMBs)、CMBs 组(CMBs):与 n-CMBs 组相比,CMBs ≥ 5 和 DI-CMBs 参与者的全局效率显著下降,特征路径长度显著增加。此外,在结节网络指标中,CMB≥5组显示左枕骨中回(MOG.L)的结节效率和结节最短路径与SCWT-A和MMSE相关,而在DI-CMBs组中,左楔状回(CUN.L)的结节最短路径与SCWT-A相关。然而,在 SL-CMBs 和 CMBs 结论中没有观察到明显的神经心理学相关性:在本研究中,CMBs 或 DI-CMBs 数量较多(≥5)的患者与白质结构网络的微观结构紊乱有关,部分影响了枕叶的视觉网络,并影响了信息处理速度和注意力等认知功能。
{"title":"Cerebral microbleeds linked to structural network disruption and cognitive impairment in white matter hyperintensities","authors":"Jiabin Yin ,&nbsp;Xia Zhou ,&nbsp;Yali Chen ,&nbsp;Yue Sun ,&nbsp;Chaojuan Huang ,&nbsp;Yating Tang ,&nbsp;Wenhao Zhu ,&nbsp;Xiaoqun Zhu ,&nbsp;Zhongwu Sun","doi":"10.1016/j.neuroscience.2024.11.027","DOIUrl":"10.1016/j.neuroscience.2024.11.027","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to explore the relationship between the cerebral microbleeds (CMBs) and white matter structural network in patients with white matter hyperintensities (WMHs), and the correlation with the cognitive impairment.</div></div><div><h3>Method</h3><div>One hundred and fifty-eight participants with WMHs underwent 3.0 T magnetic resonance imaging scans and neuropsychological assessment. The grouping method included count grading with categories: non-CMBs (n-CMBs), CMBs &lt; 5, and CMBs ≥ 5. Additionally, the distribution of CMBs was considered, distinguishing between strictly lobar CMBs (SL-CMBs) and deep or infratentorial CMBs (DI-CMBs). Diffusion tensor imaging was employed to construct the white matter structural network for each participant. Subsequently, we analyzed the correlations between the topological parameters of network and cognitive performance in individuals with CMBs.</div></div><div><h3>Results</h3><div>Compared with n-CMBs group, both CMBs ≥ 5 and DI-CMBs participants exhibited a significant decreased in global efficiency and increased in characteristic path length. Moreover, in the nodal network metrics, the CMBs ≥ 5 showed the left middle occipital gyrus (MOG.L) of nodal efficiency and nodal shortest path correlated with SCWT-A and MMSE, while in the DI-CMBs groups, the left cuneus (CUN.L) of nodal shortest path correlated with SCWT-A. However, there were no significant neuropsychological correlations observed in the SL-CMBs and CMBs &lt; 5 groups.</div></div><div><h3>Conclusion</h3><div>In this study, patients with a high count (≥5) of CMBs or DI-CMBs are associated with disruptions in the microstructure of the white matter structural network, partially impacting the visual network of occipital lobe and affecting the cognitive function of information processing speed and attention.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"564 ","pages":"Pages 31-40"},"PeriodicalIF":2.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644589","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
Combined graph convolutional networks with a multi-connection pattern to identify tremor-dominant Parkinson’s disease and Essential tremor with resting tremor 利用多连接模式的组合图卷积网络识别震颤为主的帕金森病和静止震颤的本质性震颤。
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-15 DOI: 10.1016/j.neuroscience.2024.11.030
Xiaole Zhao , Pan Xiao , Honge Gui , Bintao Xu , Hongyu Wang , Li Tao , Huiyue Chen , Hansheng Wang , Fajin Lv , Tianyou Luo , Oumei Cheng , Jing Luo , Yun Man , Zheng Xiao , Weidong Fang
Essential tremor with resting tremor (rET) and tremor-dominant Parkinson’s disease (tPD) share many similar clinical symptoms, leading to frequent misdiagnoses. Functional connectivity (FC) matrix analysis derived from resting-state functional MRI (Rs-fMRI) offers a promising approach for early diagnosis and for exploring FC network pathogenesis in rET and tPD. However, methods relying solely on a single connection pattern may overlook the complementary roles of different connectivity patterns, resulting in reduced diagnostic differentiation. Therefore, we propose a multi-pattern connection Graph Convolutional Network (MCGCN) method to integrate information from various connection modes, distinguishing between rET and healthy controls (HC), tPD and HC, and rET and tPD. We constructed FC matrices using three different connectivity modes for each subject and used these as inputs to the MCGCN model for disease classification. The classification performance of the model was evaluated for each connectivity mode. Subsequently, gradient-weighted class activation mapping (Grad-CAM) was used to identify the most discriminative brain regions. The important brain regions identified were primarily distributed within cerebellar-motor and non-motor cortical networks. Compared with single-pattern GCN, our proposed MCGCN model demonstrated superior classification accuracy, underscoring the advantages of integrating multiple connectivity modes. Specifically, the model achieved an average accuracy of 88.0% for distinguishing rET from HC, 88.8% for rET from tPD, and 89.6% for tPD from HC. Our findings indicate that combining graph convolutional networks with multi-connection patterns can not only effectively discriminate between tPD, rET, and HC but also enhance our understanding of the functional network mechanisms underlying rET and tPD.
静止性震颤(rET)和震颤为主的帕金森病(tPD)有许多相似的临床症状,因此经常被误诊。由静息态功能磁共振成像(Rs-fMRI)得出的功能连接(FC)矩阵分析为早期诊断和探索rET和tPD的FC网络发病机制提供了一种很有前景的方法。然而,仅依靠单一连接模式的方法可能会忽略不同连接模式的互补作用,从而降低诊断的区分度。因此,我们提出了一种多模式连接图卷积网络(MCGCN)方法,以整合各种连接模式的信息,区分 rET 和健康对照(HC)、tPD 和 HC 以及 rET 和 tPD。我们为每个受试者构建了三种不同连接模式的 FC 矩阵,并将其作为 MCGCN 模型的输入进行疾病分类。我们对每种连接模式的模型分类性能进行了评估。随后,梯度加权类激活图谱(Grad-CAM)被用来识别最具鉴别力的脑区。识别出的重要脑区主要分布在小脑运动皮层和非运动皮层网络中。与单一模式的 GCN 相比,我们提出的 MCGCN 模型显示出更高的分类准确性,凸显了整合多种连接模式的优势。具体来说,该模型区分 rET 和 HC 的平均准确率为 88.0%,区分 rET 和 tPD 的平均准确率为 88.8%,区分 tPD 和 HC 的平均准确率为 89.6%。我们的研究结果表明,将图卷积网络与多重连接模式相结合,不仅能有效区分 tPD、rET 和 HC,还能加深我们对 rET 和 tPD 的功能网络机制的理解。
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引用次数: 0
Short and long-term blockades of adenosine 2A, 5-HT2A, and 5-HT7 receptors induce apoptosis, reduce proliferation, and show differential effects on miR-27b-3p expression in neuroblastoma cell lines 短期和长期阻断腺苷 2A、5-HT2A 和 5-HT7 受体可诱导神经母细胞瘤细胞株凋亡、减少增殖,并对 miR-27b-3p 的表达产生不同影响。
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-14 DOI: 10.1016/j.neuroscience.2024.11.032
Kemal Erdem Basaran , Seyda Korkmaz , Güzide Satır-Basaran , Hasan Salkın
The first of our aims in this study was to investigate the effects of 5-HT2AR, 5-HT7R, and A2AR blockades on miR-27b-3p expression in the short and long-term in neuroblastoma cells. Our second aim was to reduce the expression of pERK and suppress proliferation by blocking the 5-HT2AR with ketanserin. Our third aim was to reduce the expression of pAKT and induce apoptosis by blocking the A2AR and 5-HT7R with MSX3 and SB269970. Thus, we aimed to investigate the therapeutic efficacy of ketanserin, MSX3 and SB269970, individually or in combination, on neuroblastoma cells.
We found that short and long-term blockades of A2A, 5-HT2A, and 5-HT7 receptors had different effects on miR-27b-3p expression. Blockade of A2AR and 5-HT7R with MSX3 and SB269970 decreased miR-27b-3p expression in the short term while increasing it in the long term. Ketanserin increased miR-27b-3p expression in both the short and long term. When 5-HT2AR was blocked with ketanserin, no significant difference was observed in pERK expression and proliferation in the short term. In contrast, a substantial decrease in pERK expression and proliferation was detected in the long term. Our findings show that the MSX3 + SB269970 dual combination and ketanserin + MSX3 + SB269970 triple combination are especially critical in suppressing pAKT expression in the long term. These findings showed that pAKT protein expression induced apoptosis due to decreased in neuroblastoma cells.
Our study provides the first evidence for the relationships between ketanserin/miR-27b-3p/pERK, MSX3/miR-27b-3p/pAKT, and SB269970/miR-27b-3p/pAKT in neuroblastoma cells. Ketanserin, MSX3, and SB269970 drug combinations may be promising therapeutic agents in neuroblastoma cells.
本研究的第一个目的是研究 5-HT2AR、5-HT7R 和 A2AR 阻断对神经母细胞瘤细胞中 miR-27b-3p 表达的短期和长期影响。我们的第二个目的是通过酮塞林阻断 5-HT2AR 减少 pERK 的表达并抑制增殖。我们的第三个目标是通过使用 MSX3 和 SB269970 阻断 A2AR 和 5-HT7R 来减少 pAKT 的表达并诱导细胞凋亡。因此,我们旨在研究酮塞林、MSX3 和 SB269970 单独或联合使用对神经母细胞瘤细胞的疗效。我们发现,短期和长期阻断 A2A、5-HT2A 和 5-HT7 受体对 miR-27b-3p 的表达有不同的影响。用 MSX3 和 SB269970 阻断 A2AR 和 5-HT7R 会在短期内减少 miR-27b-3p 的表达,而在长期内则会增加。酮塞林能在短期和长期内增加 miR-27b-3p 的表达。当用酮塞林阻断 5-HT2AR 时,短期内 pERK 的表达和增殖没有明显差异。与此相反,pERK 的表达和增殖在长期内大幅减少。我们的研究结果表明,MSX3 + SB269970 双联疗法和酮塞林 + MSX3 + SB269970 三联疗法在长期抑制 pAKT 表达方面尤为关键。这些研究结果表明,神经母细胞瘤细胞中 pAKT 蛋白表达减少会诱导细胞凋亡。我们的研究首次证明了神经母细胞瘤细胞中酮色林/miR-27b-3p/pERK、MSX3/miR-27b-3p/pAKT和SB269970/miR-27b-3p/pAKT之间的关系。酮塞林、MSX3和SB269970药物组合可能是治疗神经母细胞瘤细胞的有效药物。
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引用次数: 0
Comparison of the efficacy of updated drugs for the treatment on the improvement of cognitive function in patients with Alzheimer 's disease: A systematic review and network meta- analysis. 比较最新药物对改善阿尔茨海默病患者认知功能的疗效:系统综述和网络荟萃分析。
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-14 DOI: 10.1016/j.neuroscience.2024.11.029
Weili Cao, Bo Zhu, Zhiqin Liu, Xiaotao Jia, Hongwei Zhao, Naibing Gu, Hongye Chang, Jing Xi, Rong Li, Kun Guo, Jia Shen, Le Ding, Fanya Sun, Zhengli Di

Background: The recent emergence of updated drugs for the treatment of Alzheimer's disease (AD) has produced encouraging cognitive and clinical results in clinical trials, but there is still controversy over how to choose effective treatment options among these numerous drugs. The purpose of this network meta-analysis (NMA) is to compare and rank these drugs based on their efficacy.

Methods: We systematically searched in PubMed, Web of Science databases and Cochrane LIbrary, gov for randomized controlled trials for data from 2020 to 2024, and then performed a random-effect network meta-analysis.

Results: Our NMA results showed that in several main indicators ADAS-cog, CDR-SB and ADCS-ADL. GV-971 (MD -2.36, 95 % CI -5.08, 0.35), Lecanemab (MD -2.00, 95 % CI -5.25, 1.26), Donanemab (MD -1.45, 95 % CI -4.70, 1.81), Masupirdine (MD -0.83, 95 % CI -3.49, 1.84) were more effective than placebo in improving ADAS-cog. In terms of CDR-SB, Lecanemab (MD -3.11,95 % CI -5.23, -0.99) was more effective. Compared with placebo, Donanemab was more effective in ADCS-ADL (MD 3.26,95 % CI 1.48,5.05). SUCRA values showed that GV-971 (76.1 % and 68.7 %) could achieve better therapeutic effects in ADAS-cog) and NPI, and Lecanema (98.1 %) was more effective in improving CDR-SB scores than other drugs. Donanemab (99.8 %) may be the most promising way to slow down the decline in ADCS-ADL scores. The effect of Masupirdine (80.7 %) on MMSE was significantly better than that of several other drugs.

Conclusion: Donanemab and Lecanemab showed good efficacy in ADCS-ADL and CDR-SB, respectively. GV-971 is the best choice to improve ADAS cogs and NPI.

背景:最近,治疗阿尔茨海默病(AD)的新药不断涌现,在临床试验中取得了令人鼓舞的认知和临床结果,但如何在众多药物中选择有效的治疗方案仍存在争议。本网络荟萃分析(NMA)的目的是根据疗效对这些药物进行比较和排序:我们在 PubMed、Web of Science 数据库和 Cochrane LIbrary、gov 中系统检索了 2020 年至 2024 年的随机对照试验数据,然后进行了随机效应网络荟萃分析:GV-971(MD -2.36,95 % CI -5.08,0.35)、Lecanemab(MD -2.00,95 % CI -5.25,1.26)、Donanemab(MD -1.45,95 % CI -4.70,1.81)、Masupirdine(MD -0.83,95 % CI -3.49,1.84)在改善ADAS-cog方面比安慰剂更有效。就 CDR-SB 而言,Lecanemab(MD -3.11,95 % CI -5.23,-0.99)更为有效。与安慰剂相比,多奈单抗在 ADCS-ADL 方面更有效(MD 3.26,95 % CI 1.48,5.05)。SUCRA 值显示,GV-971(76.1% 和 68.7%)在 ADAS-cog)和 NPI 方面的疗效更好,Lecanema(98.1%)在改善 CDR-SB 评分方面比其他药物更有效。多奈单抗(99.8%)可能是最有希望减缓 ADCS-ADL 评分下降的方法。Masupirdine(80.7%)对MMSE的效果明显优于其他几种药物:结论:多那尼单抗和来卡尼单抗分别在 ADCS-ADL 和 CDR-SB 方面显示出良好的疗效。GV-971是改善ADAS cogs和NPI的最佳选择。
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