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Tight Junction Proteins and Bacterial Pathogens Impacting the Brain 紧密连接蛋白和影响大脑的细菌病原体
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-11-29 DOI: 10.1111/ejn.70340
Mazen M. Jamil Al-Obaidi, Mohd Nasir Mohd Desa, AbdulRahman Muthanna

The blood–brain barrier (BBB) is an essential protective structure that preserves the homeostasis of the central nervous system (CNS) by controlling the transfer of chemicals and infections from the bloodstream into the tissues of the brain. The BBB is primarily composed of brain microvascular endothelial cells (BMECs), which are closely linked by tight junction (TJ) proteins, including occludin, claudins and junctional adhesion molecules (JAMs). However, certain bacterial infections, such as those caused by Escherichia coli (E. coli), Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae), have developed strategies to compromise these TJs, facilitating their invasion of the CNS and resulting in meningitis. These bacteria utilise several virulence factors, including outer membrane proteins, pili and toxins, to modify host cell signalling pathways, compromise the BBB and facilitate their translocation across barriers. This study aims to clarify the molecular processes employed by these pathogens to penetrate the BBB, with an emphasis on their effects on TJ integrity. A comprehension of these mechanisms is essential for formulating effective medicines to prevent and cure bacterial meningitis by safeguarding or restoring BBB integrity.

血脑屏障(BBB)是一个重要的保护结构,通过控制化学物质和感染从血液到大脑组织的转移来保持中枢神经系统(CNS)的稳态。血脑屏障主要由脑微血管内皮细胞(BMECs)组成,这些细胞通过紧密连接(TJ)蛋白紧密连接,包括occludin, claudin和junctional adhesion molecules (JAMs)。然而,某些细菌感染,如由大肠杆菌(E. coli)、脑膜炎奈瑟菌(N. meningitidis)、肺炎链球菌(S. pneumoniae)和流感嗜血杆菌(H. influenzae)引起的感染,已经形成了损害这些TJs的策略,促进它们侵入中枢神经系统并导致脑膜炎。这些细菌利用几种毒力因子,包括外膜蛋白、菌毛和毒素,来改变宿主细胞信号通路,破坏血脑屏障并促进其跨屏障易位。本研究旨在阐明这些病原体穿透血脑屏障的分子过程,重点研究它们对血脑屏障完整性的影响。了解这些机制对于制定有效药物,通过保护或恢复血脑屏障完整性来预防和治疗细菌性脑膜炎至关重要。
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引用次数: 0
Optimized Simultaneous Assessment of Subcortical and Cortical Auditory Responses Through a Frequency-Tagged Roving Paradigm 通过频率标记漫游范式优化皮层下和皮层听觉反应的同时评估
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-11-29 DOI: 10.1111/ejn.70337
Xiaoyu Wang, Loretta Norton, Teneille E. Gofton, Derek B. Debicki, Marat Slessarev, Adrian M. Owen

Assessment of auditory-evoked responses across multiple stages of the ascending auditory pathway provides complementary insights into neural integrity for research and clinical contexts. However, traditional approaches, constrained by conflicting optimal parameters, require separate sessions for different response types, limiting efficiency and preventing simultaneous multi-level assessment, while evidence of individual-level sensitivity and reliability remains limited. We aimed to develop and validate a paradigm enabling concurrent, single-subject assessment of frequency-following responses (FFRs), auditory steady-state responses (ASSRs), and event-related potentials (ERPs) spanning subcortical to cortical levels. Two amplitude-modulated tones (carriers at 220/440 Hz, modulated at 40/80 Hz) were presented in a roving sequence so that each tone served as both standard and deviant, and EEG was recorded using a two-electrode montage (Fz, Cz) EEG setup. In 32 healthy participants, the paradigm achieved 100% sensitivity for high-frequency FFRs and gamma-band ASSRs, confirmed by permutation-based spectral analysis. Machine-learning classification distinguished stimulus conditions from resting state based on N1 and sustained negativity in all participants (32/32), confirming robust single-subject detection of obligatory cortical responses. Directional asymmetry was observed in transition responses: ascending frequency transitions predominantly elicited enhanced N1–P2-like responses (32/32), whereas descending transitions evoked mismatch negativity–like (MMN-like) responses in 30/32 participants. Recording-duration analysis showed that overall detection sensitivity across response components reached 0.91 after 27 min of recording. Collectively, these findings indicate that the frequency-tagged roving paradigm provides a framework for characterizing auditory processing across hierarchical levels within a single session, supporting potential use in future experimental and translational studies.

听觉诱发反应的评估跨越上升听觉通路的多个阶段,为研究和临床环境提供了对神经完整性的补充见解。然而,传统方法受到最优参数冲突的限制,需要对不同的响应类型进行单独的会话,限制了效率,并且无法同时进行多层次评估,而个人层面的敏感性和可靠性的证据仍然有限。我们的目标是开发并验证一种范式,该范式能够并发地、单受试者评估频率跟随反应(FFRs)、听觉稳态反应(ASSRs)和跨越皮层下到皮层水平的事件相关电位(ERPs)。两个调幅音调(220/440 Hz的载波,40/80 Hz的调制)以漫游顺序呈现,以便每个音调同时作为标准和偏差,并使用双电极蒙太奇(Fz, Cz) EEG设置记录EEG。在32名健康参与者中,该模式对高频ffr和伽马波段assr的灵敏度达到100%,这一点得到了基于排列的频谱分析的证实。机器学习分类区分了刺激条件和静息状态,基于N1和所有参与者的持续负性(32/32),证实了单受试者强制性皮层反应的强大检测。在转换反应中观察到方向不对称:上升频率转换主要引起增强的n1 - p2样反应(32/32),而下降频率转换在30/32参与者中引起错配负性样(mmn样)反应。记录时间分析表明,记录27 min后,各响应分量的总体检测灵敏度达到0.91。总的来说,这些发现表明,频率标记的漫游范式为表征单次会话中跨层次的听觉处理提供了一个框架,支持在未来实验和转化研究中的潜在应用。
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引用次数: 0
Expanding Therapeutic Horizons in Parkinson's Disease Through MicroRNA-Based Interventions: A Comprehensive Review 通过基于微rna的干预扩大帕金森病的治疗视野:一项综合综述
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-11-29 DOI: 10.1111/ejn.70343
Utkarsh U. Bhamare, Anishka Talpade, Ravindra Babu Pingili, Mahesh B. Palkar

Parkinson's disease (PD) is a neurodegenerative disorder with rapidly increasing prevalence, characterized by dopaminergic neuronal loss and α-synuclein aggregation. Current therapies provide only symptomatic benefit and do not alter the disease course. MicroRNAs (miRNAs), small noncoding RNAs that regulate gene expression, are increasingly recognized as key modulators of PD pathogenesis, influencing oxidative stress, mitochondrial dysfunction, neuroinflammation, and proteostasis. Therapeutic modulation of miRNAs in PD has centered on two complementary approaches: miRNA inhibitors (antagomiRs), which silence pathogenic miRNAs, and miRNA mimics (agomiRs), which restore the activity of protective ones. This review integrates current insights into miRNA dysregulation in PD and evaluates the hurdles limiting therapeutic translation. Specific miRNAs such as miR-7, miR-153, and miR-34b/c directly regulate SNCA expression, whereas others influence clearance pathways and stress responses. Although miRNA-based therapeutics offer considerable promise, their clinical utility remains constrained by challenges of delivery, specificity, and standardization. This review highlights strategies to harness miRNA modulation as a targeted therapeutic avenue in PD.

帕金森病(PD)是一种患病率迅速上升的神经退行性疾病,其特征是多巴胺能神经元丧失和α-突触核蛋白聚集。目前的治疗方法只提供症状上的益处,并不能改变病程。MicroRNAs (miRNAs)是一种调节基因表达的小非编码rna,越来越被认为是帕金森病发病的关键调节剂,影响氧化应激、线粒体功能障碍、神经炎症和蛋白质平衡。PD中miRNA的治疗调节主要集中在两种互补的方法上:miRNA抑制剂(antagomiRs)和miRNA模拟物(agomiRs),前者沉默致病性miRNA,后者恢复保护性miRNA的活性。这篇综述整合了目前对PD中miRNA失调的见解,并评估了限制治疗转化的障碍。特异性mirna如miR-7、miR-153和miR-34b/c直接调节SNCA表达,而其他mirna则影响清除途径和应激反应。尽管基于mirna的治疗提供了相当大的希望,但它们的临床应用仍然受到递送、特异性和标准化挑战的限制。这篇综述强调了利用miRNA调节作为PD靶向治疗途径的策略。
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引用次数: 0
Knocking at the Doors of Perception: Relating LSD Effects on Low-Frequency Fluctuations and Regional Homogeneity to Receptor Densities in fMRIf 敲开感知之门:LSD对低频波动和区域均匀性与fmri受体密度的影响
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-11-26 DOI: 10.1111/ejn.70338
Paolo La-Torraca-Vittori, Livio Tarchi, Elisa Arrigo, Stefano Lanterna, Eleonora Tosi, Arne Doose, Fulvia Palesi, Doris Pischedda, Valdo Ricca, Paolo Fusar-Poli, Stefano Damiani

Despite a renewed scientific interest in lysergic acid diethylamide (LSD), its local neural effects remain underexplored. This functional magnetic resonance imaging (fMRI) study explored and compared LSD-induced changes in local activity (amplitude of low-frequency fluctuations: ALFF) and local connectivity (regional homogeneity: ReHo), assessing their relationship to regional receptor density. Imaging data of 15 healthy adults from an open dataset were analyzed. For each participant, two pairs of resting-state runs were available (rest1 and rest2), one performed under placebo and one following the intravenous administration of 75-μg LSD. Voxel-wise paired t-tests compared ALFF and ReHo in the LSD versus placebo conditions. Rest1*rest2 test–retest reliability and ALFF*ReHo cross-modal associations were assessed with conjunction maps and vertex-wise correlations. Finally, neurochemical enrichment analyses related LSD-induced ALFF and ReHo changes to cortical density maps of LSD-related neurotransmitter receptors and transporters. Both ALFF and ReHo decreased in somatosensory/visual cortices under LSD compared to placebo. Specific decreases were observed for ALFF in associative regions belonging to the default mode and frontoparietal networks, and for ReHo in subcortical regions (cluster-based corrected p < 0.05). Test–retest reliability was high for ALFF (rho = 0.80, p = 0.001) and moderate for ReHo (rho = 0.46, p = 0.001). ALFF*ReHo LSD-induced changes were moderately associated (rest1: rho = 0.36, p = 0.001; rest2: rho = 0.56, p = 0.001). Neurochemical enrichment analysis showed that LSD-induced ALFF/ReHo alterations were reliably and negatively correlated with the density of D2 and 5-HT1A receptors (FDR-corrected p < 0.05). These preliminary findings suggest that LSD may engage complex and dynamic neurochemical processes beyond its known 5-HT2A receptor target, warranting further investigation.

尽管科学界对麦角酸二乙胺(LSD)重新产生了兴趣,但其局部神经效应仍未得到充分研究。这项功能性磁共振成像(fMRI)研究探索并比较了lsd诱导的局部活动(低频波动幅度:ALFF)和局部连通性(区域均匀性:ReHo)的变化,评估了它们与区域受体密度的关系。分析了来自开放数据集的15名健康成人的成像数据。对于每个参与者,有两对静息状态运行(rest1和rest2),一组在安慰剂下进行,另一组在静脉注射75 μg LSD后进行。体素配对t检验比较了LSD组和安慰剂组的ALFF和ReHo。Rest1*rest2测试-重测信度和ALFF*ReHo跨模态关联通过连接图和顶点相关进行评估。最后,神经化学富集分析了lsd诱导的ALFF和ReHo变化对lsd相关神经递质受体和转运体的皮质密度图的影响。与安慰剂相比,LSD组体感觉/视觉皮层的ALFF和ReHo均有所下降。在属于默认模式和额顶叶网络的联合区域中观察到ALFF的特异性降低,在皮层下区域中观察到ReHo的特异性降低(基于聚类的校正p <; 0.05)。ALFF的重测信度高(rho = 0.80, p = 0.001), ReHo的重测信度中等(rho = 0.46, p = 0.001)。ALFF*ReHo与lsd诱导的变化中度相关(rest1: rho = 0.36, p = 0.001; rest2: rho = 0.56, p = 0.001)。神经化学富集分析显示,lsd诱导的ALFF/ReHo改变与D2和5-HT1A受体的密度呈可靠的负相关(fdr校正p <; 0.05)。这些初步发现表明,LSD可能参与复杂和动态的神经化学过程,而不是其已知的5-HT2A受体目标,值得进一步研究。
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引用次数: 0
The Somatosensory Mismatch Negativity 体感失配消极。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-11-25 DOI: 10.1111/ejn.70301
Miro Grundei, Wolfger von der Behrens, Piia Astikainen, Nicole Wetzel, Felix Blankenburg

Mismatch negativity (MMN) is a well-established neural signature of automatic change detection in the auditory modality. Growing evidence suggests that analogous responses exist in other sensory domains, including somatosensation. This review provides an initial overview of the somatosensory MMN (sMMN), summarizing findings from both human and animal research concerning its underlying neural mechanisms and functional significance as a predictive error signal. We discuss electrophysiological and neuroimaging evidence identifying primary and secondary somatosensory cortices (S1 and S2) as key generators of the sMMN, highlighting the roles of sensory and stimulus-specific adaptation, as well as true deviance detection or surprise. Computational studies further support a hierarchical inference process, where somatosensory mismatch responses encode probabilistic structures based on transition probabilities of sequential input. We also address the clinical relevance of the sMMN in neurodevelopmental, psychiatric, and neurological disorders, as well as its role in aging and body representation. Understanding the neuronal mechanisms underlying the sMMN not only advances our knowledge of somatosensory predictive processing but also contributes to the broader study of perception and learning in the brain.

失配负性(MMN)是一种成熟的听觉模态自动变化检测的神经特征。越来越多的证据表明,类似的反应存在于其他感官领域,包括躯体感觉。这篇综述提供了体感MMN (sMMN)的初步概述,总结了人类和动物研究中关于其潜在神经机制和作为预测误差信号的功能意义的发现。我们讨论了电生理和神经影像学证据,确定初级和次级体感觉皮层(S1和S2)是sMMN的关键产生器,强调了感觉和刺激特异性适应的作用,以及真正的偏差检测或惊喜。计算研究进一步支持分层推理过程,其中体感失配响应基于顺序输入的转移概率编码概率结构。我们还讨论了sMMN在神经发育、精神和神经疾病中的临床相关性,以及它在衰老和身体表征中的作用。了解sMMN背后的神经元机制不仅可以提高我们对体感预测处理的认识,而且有助于更广泛地研究大脑的感知和学习。
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引用次数: 0
The Effect of Previously Encountered Sensory Information on Neural Representations of Predictability: Evidence From Human EEG 先前遇到的感觉信息对可预测性神经表征的影响:来自人类脑电图的证据。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-11-25 DOI: 10.1111/ejn.70300
Kaho Magami, Roberta Bianco, Edward Hall, Marcus Pearce, Maria Chait

Accumulating evidence suggests that the brain continuously monitors the predictability of rapidly evolving sound sequences, even when they are not behaviorally relevant. An increasing body of empirical evidence links sustained tonic M/EEG activity to evidence accumulation and tracking the predictability, or inferred precision, of the auditory stimulus. However, it remains unclear whether, and how, this process depends on auditory contextual memory. We investigated how the history of sound sequences influences the neural representation of ongoing regularity under different structural contexts. We recorded EEG responses from naïve participants passively listening to sequences of 50-ms tone-pips across two experiments and compared these responses to predictions from ideal observer models with varying memory spans. In Experiment 1 (N = 26; both sexes), a regularly repeating sequence of 10 tones transitioned directly to a different regular sequence. In Experiment 2 (N = 28; both sexes), the same regular sequence was repeated after an intervening random segment. Results showed that in Experiment 1, neural responses were best explained by models with minimal memory. In contrast, in Experiment 2, inferred predictability of the resumed sequence was influenced by the intervening random tones, even several seconds after the interruption, indicating that the brain retains contextual memory over time. This dissociation implies that the brain can dynamically adjust its strategy based on inferred environmental structure—resetting context when interruptions signal change and preserving context when patterns are likely to resume.

越来越多的证据表明,大脑不断地监控着快速进化的声音序列的可预测性,即使它们与行为无关。越来越多的经验证据将持续的脑电活动与证据积累和追踪听觉刺激的可预测性或推断精度联系起来。然而,目前尚不清楚这个过程是否以及如何依赖于听觉上下文记忆。我们研究了声音序列的历史如何影响不同结构背景下持续规律的神经表征。我们记录了naïve参与者在两个实验中被动聆听50毫秒音点序列的脑电图反应,并将这些反应与不同记忆广度的理想观察者模型的预测进行了比较。在实验1中(N = 26,男女),一个有规律重复的10个音调序列直接过渡到一个不同的规律序列。在实验2 (N = 28,男女)中,在中间的随机片段后重复相同的规则序列。结果表明,在实验1中,最小记忆模型最能解释神经反应。相反,在实验2中,重新开始的序列的推断可预测性受到干预的随机音调的影响,甚至在中断几秒钟后,这表明大脑随着时间的推移保留了上下文记忆。这种分离意味着大脑可以根据推断的环境结构动态调整其策略——当中断信号发生变化时重置上下文,当模式可能恢复时保留上下文。
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引用次数: 0
Reorganized Functional Networks Underlie Working Memory Deficits After Right-Hemispheric Stroke 右半脑卒中后工作记忆缺陷的功能网络重组。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-11-24 DOI: 10.1111/ejn.70336
Emilie Marti, Sélim Yahia Coll, Naz Doganci, Radek Ptak

Working memory (WM) is a core component of higher-order cognition, and its impairment is a common consequence of stroke. While traditional lesion-symptom mapping highlights focal damage, it often overlooks alterations in large-scale brain network dynamics. This study investigated WM deficits through functional connectivity (FC) analyses of frontoparietal networks in 34 patients with right hemisphere (RH) stroke and 35 healthy controls. Resting-state fMRI was used to examine region-of-interest and whole-brain seed-to-voxel FC in relation to WM performance on verbal and spatial N-back tasks. Compared to controls, stroke patients exhibited disrupted FC-WM associations, characterized by reduced intrahemispheric FC between anterior and posterior RH regions, which correlated with poorer WM performance. Notably, enhanced interhemispheric FC, particularly between the right middle and inferior frontal gyri and contralateral parietal cortices, was positively associated with WM accuracy, suggesting compensatory engagement of the intact hemisphere. No performance differences were observed between task modalities, supporting the involvement of domain-general WM mechanisms. These findings highlight the role of early network-level reorganization in shaping cognitive outcomes post-stroke. Specifically, WM deficits appear to result not solely from structural damage but from altered FC patterns, where reduced intrahemispheric connectivity may be mitigated by adaptive interhemispheric recruitment.

工作记忆(WM)是高阶认知的核心组成部分,其功能障碍是脑卒中的常见后果。虽然传统的病变症状映射强调局灶性损伤,但它往往忽略了大规模脑网络动力学的变化。本研究通过对34例右半球(RH)卒中患者和35名健康对照者的额顶叶网络功能连接(FC)分析来研究WM缺陷。静息状态fMRI用于检测兴趣区和全脑种子到体素FC与语言和空间N-back任务中WM表现的关系。与对照组相比,卒中患者表现出FC-WM关联中断,其特征是前后RH区域之间的半球内FC减少,这与较差的WM表现相关。值得注意的是,增强的半球间FC,特别是在右侧额叶中下回和对侧顶叶皮层之间,与WM准确性呈正相关,表明完整半球的代偿性参与。任务模式之间没有观察到表现差异,支持领域通用WM机制的参与。这些发现强调了早期网络水平重组在塑造中风后认知结果中的作用。具体来说,WM缺陷似乎不仅仅是由结构损伤引起的,而且是由FC模式改变引起的,其中半球内连通性减少可能通过适应性半球间招募来缓解。
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引用次数: 0
hsa-miR-22-3p-Mediated Exosome Release From Neurons Induces Apoptosis in Recipient Glial and Neuronal Cells in Parkinson's Disease Stress Conditions hsa- mir -22-3p介导的神经元外泌体释放诱导帕金森病应激条件下受体胶质细胞和神经元细胞凋亡
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-11-24 DOI: 10.1111/ejn.70342
Shatakshi Shukla, Shanikumar Goyani, Dipanwita Chakraborty, M. V. Saranga, Minal Mane, Nisha Chandak, Jyoti Singh, Fatema Currim, Anjali Shinde, Sumedha Shah, Shyam Kishore, Bhumika Wadhwa, Sharad Gupta, Rajesh Singh

Exosome-mediated intercellular communication between different cell types and brain regions is essential for the homeostasis of the nervous system and any dysfunctions lead to the progression of several neurodegenerative disorders including Parkinson's disease (PD). Exosome biogenesis and release from the specific cell types are modulated by interorganellar crosstalk, and the transfer of exosomal cargo influences the functional outcome in the recipient cells. The miRNA–mRNA interaction modulates mRNA translation and stability; yet the understanding of specific miRNAs modulating exosome release in neuronal cells during PD stress is not well characterized. Bioinformatics analysis of different databases identified the putative mRNA targets for hsa-miR-22-3p suggesting its regulatory role in pathways of exosome release, autophagy and apoptosis. hsa-miR-22-3p levels were downregulated in neuronal SH-SY5Y cells under PD stress conditions induced by 6-OHDA and rotenone. hsa-miR-22-3p expression downregulates LAMP1, BCL2 and p62 protein levels in neuronal cells, impairing autophagic flux and mitochondrial-lysosomal functions, enhancing exosome release. Exosomes derived from hsa-miR-22-3p-expressing neuronal cells were actively internalized by glial and neuronal cells, exhibiting distinctive morphological features and cell death. The present study highlights the role of hsa-miR-22-3p in modulating the interorganelle communication, influencing exosome release and exacerbating neuronal and glial cell death during PD stress conditions.

外泌体介导的不同细胞类型和大脑区域之间的细胞间通讯对于神经系统的稳态至关重要,任何功能障碍都会导致包括帕金森病(PD)在内的几种神经退行性疾病的进展。外泌体的生物发生和特定细胞类型的释放受细胞器间串扰调节,外泌体货物的转移影响受体细胞的功能结果。miRNA-mRNA相互作用调节mRNA的翻译和稳定性;然而,对PD应激下神经元细胞中调节外泌体释放的特异性miRNAs的理解尚未得到很好的表征。不同数据库的生物信息学分析确定了hsa-miR-22-3p的推定mRNA靶点,表明其在外泌体释放、自噬和凋亡途径中的调节作用。在6-OHDA和鱼烯酮诱导的PD应激条件下,神经元SH-SY5Y细胞中hsa-miR-22-3p水平下调。hsa-miR-22-3p表达下调神经元细胞中LAMP1、BCL2和p62蛋白水平,损害自噬通量和线粒体-溶酶体功能,增强外泌体释放。来源于表达hsa- mir -22-3p的神经元细胞的外泌体被胶质细胞和神经元细胞积极内化,表现出独特的形态特征和细胞死亡。本研究强调了hsa-miR-22-3p在PD应激条件下调节细胞器间通讯、影响外泌体释放和加剧神经元和胶质细胞死亡中的作用。
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引用次数: 0
Neural Immunoglobulins Shape Brain Circuits 神经免疫球蛋白塑造脑回路。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-11-24 DOI: 10.1111/ejn.70330
Michel Salzet

Mounting evidence challenges the view that antibodies reach the brain solely via vascular leaks. Neurons, astrocytes and microglia appear able to assemble restricted and context-dependent immunoglobulin repertoires via cryptic V(D)J recombination, splice-and-link RNA editing and retroelement-assisted rearrangements. These endogenous antibodies have been associated with complement-mediated pruning, receptor trafficking and astrocyte–neuron metabolic coupling and may change after injury. However, causal evidence from in vivo, cell-type–specific gain- or loss-of-function models remains sparse. Accordingly, we synthesise current evidence and outline testable, conservative hypotheses about when and how neural immunoglobulins might influence CNS function and disease.

越来越多的证据挑战了抗体只能通过血管渗漏到达大脑的观点。神经元、星形胶质细胞和小胶质细胞似乎能够通过隐式V(D)J重组、剪接链接RNA编辑和逆转录元件辅助重排来组装受限的和环境依赖性的免疫球蛋白库。这些内源性抗体与补体介导的修剪、受体运输和星形胶质细胞-神经元代谢偶联有关,并可能在损伤后发生变化。然而,来自体内的因果证据,细胞类型特异性的功能增益或丧失模型仍然很少。因此,我们综合目前的证据,并概述可测试的,关于神经免疫球蛋白何时以及如何影响中枢神经系统功能和疾病的保守假设。
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引用次数: 0
Aversion Encoding and Behavioral State Modulation of Physiologically Defined Cell Types in the Lateral Habenula 侧缰中生理定义细胞类型的厌恶编码和行为状态调节。
IF 2.4 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-11-24 DOI: 10.1111/ejn.70302
Ioannis S. Zouridis, Lisa Schmors, Salvatore Lecca, Mauro Congiu, Manuel Mameli, Philipp Berens, Fabio Monteiro, Patricia Preston-Ferrer, Andrea Burgalossi

The lateral habenula (LHb) integrates aversive information to regulate motivated behaviors. Despite recent advances in identifying neuronal diversity at the molecular level, in vivo electrophysiological diversity of LHb neurons remains poorly understood. Understanding this diversity is essential for deciphering how information is processed in the LHb. To address this gap, we conducted in vivo juxtacellular recording and labeling of single LHb neurons in mice. Morphological analysis revealed a direct axonal projection of LHb neurons to the mediodorsal thalamus. To analyze in vivo LHb firing patterns, we applied an unsupervised clustering algorithm. This analysis identified four distinct spontaneous firing patterns of LHb neurons, which were consistent across both anesthetized and awake states. To determine whether these firing patterns correlate with function, we recorded neuronal responses to foot shock stimulation in anesthetized mice and monitored spontaneous behavior in awake mice. We found that low-firing, bursting neurons were preferentially modulated by foot shocks in anesthetized mice and also tracked behavioral states in awake mice. Collectively, our findings indicate significant electrophysiological diversity among LHb neurons, which is associated with their modulation by aversive stimuli and behavioral state.

侧habenula (LHb)整合厌恶信息来调节动机行为。尽管最近在分子水平上识别神经元多样性方面取得了进展,但LHb神经元的体内电生理多样性仍然知之甚少。了解这种多样性对于破译LHb中信息的处理方式至关重要。为了解决这一空白,我们在小鼠体内对单个LHb神经元进行了细胞旁记录和标记。形态学分析显示LHb神经元直接轴突投射到丘脑中背侧。为了分析体内LHb的放电模式,我们采用了一种无监督聚类算法。该分析确定了LHb神经元的四种不同的自发放电模式,这些模式在麻醉和清醒状态下都是一致的。为了确定这些放电模式是否与功能相关,我们记录了麻醉小鼠对足部电击刺激的神经元反应,并监测了清醒小鼠的自发行为。我们发现,在麻醉小鼠中,低放电、破裂的神经元优先受到足部电击的调节,并追踪清醒小鼠的行为状态。总的来说,我们的研究结果表明LHb神经元之间存在显著的电生理多样性,这与它们受厌恶刺激和行为状态的调节有关。
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European Journal of Neuroscience
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