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Editorial: Role of ion channels and metabotropic receptors in oligodendrogliogenesis: novel targets for demyelinating pathologies. 社论:离子通道和代谢受体在少突胶质细胞生成中的作用:脱髓鞘病变的新靶点。
IF 4.2 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-12 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1517363
Federica Cherchi, Matthew Swire, Davide Lecca
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引用次数: 0
Does age protect against loss of tonotopy after acute deafness in adulthood? 成年后急性耳聋后,年龄是否能防止音调损失?
IF 4.2 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-08 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1424773
Nicole Rosskothen-Kuhl, Sarah Green, Till F Jakob

The mammalian auditory system develops a topographical representation of sound frequencies along its pathways, also called tonotopy. In contrast, sensory deprivation during early development results in no or only rudimentary tonotopic organization. This study addresses two questions: (1) How robust is the central tonotopy when hearing fails in adulthood? (2) What role does age play at time of deafness? To address these questions, we deafened young and old adult rats with previously normal hearing. One month after deafening, both groups were unilaterally supplied with cochlear implants and electrically stimulated for 2 h. The central auditory neurons, which were activated as a result of the local electrical intracochlear stimulation, were visualized using Fos staining. While the auditory system of young rats lost the tonotopic organization throughout the brainstem, the auditory system of the older rats mainly sustained its tonotopy. It can be proposed that plasticity prevails in the central auditory system of young adult rats, while network stability prevails in the brains of aging rats. Consequently, age may be an important factor in protecting a hearing-experienced adult auditory system from a rapid loss of tonotopy when suffering from acute hearing loss. Furthermore, the study provides compelling evidence that acute deafness in young adult patients should be diagnosed as early as possible to prevent maladaptation of the central auditory system and thus achieve the optimal hearing outcome with a hearing prosthesis.

哺乳动物的听觉系统会沿着其通路形成声音频率的地形表征,也称为音调表征。与此相反,早期发育过程中的感官剥夺会导致没有或仅有基本的声调组织。本研究探讨了两个问题:(1) 当成年期听力衰退时,中央音调组织的稳健性如何?(2)年龄在耳聋时起什么作用?为了解决这些问题,我们对以前听力正常的青年和老年成年大鼠进行了耳聋治疗。耳聋一个月后,给两组大鼠单侧植入人工耳蜗,并对其进行2小时的电刺激,用Fos染色法观察因局部蜗内电刺激而被激活的听觉中枢神经元。年轻大鼠的听觉系统失去了整个脑干的音调组织,而年长大鼠的听觉系统则主要保持了音调组织。可以认为,年轻成年大鼠的中枢听觉系统具有可塑性,而衰老大鼠的大脑则具有网络稳定性。因此,年龄可能是保护听觉经验丰富的成年听觉系统的一个重要因素,使其在遭受急性听力损失时不至于迅速丧失音调。此外,该研究还提供了令人信服的证据,证明应尽早诊断年轻成年患者的急性耳聋,以防止中枢听觉系统适应不良,从而通过安装助听器达到最佳听力效果。
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引用次数: 0
Panaroma of microglia in traumatic brain injury: a bibliometric analysis and visualization study during 2000-2023. 创伤性脑损伤中的小胶质细胞全貌:2000-2023 年期间的文献计量分析和可视化研究。
IF 4.2 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-07 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1495542
Yuhang Zhang, Tingzhen Deng, Xiao Ding, Xingyuan Ma, Yatao Wang, Haijun Yang, Ruiwen Ding, Dawen Wang, Haotian Li, Maohua Zheng

Background: Traumatic brain injury (TBI) is a critical global health concern characterized by elevated rates of both morbidity and mortality. The pathological and physiological changes after TBI are closely related to microglia. Microglia, the primary immune cells in the brain, are closely linked to the mechanisms and treatment of TBI. With increasing research in this area, this study employs bibliometric analysis to identify current research hotspots and predict future trends.

Objective: We decided to perform a bibliometric analysis to provide a comprehensive overview of the advancements in microglia research related to traumatic brain injury. We aim to offer researchers insights into current trends and future research directions.

Method: We collected all articles and reviews related to microglia and traumatic brain injury published between 2000 and 2023 from the Web of Science Core Collection. These records were analyzed using VOSviewer, CiteSpace, and the R package "bibliometrix".

Results: We retrieved 665 publications from 25 countries, with the majority contributed by the United States and China. The number of publications on traumatic brain injury and microglia has been steadily increasing each year. Our analysis highlighted the Journal of Neurotrauma and the Journal of Neuroinflammation as the most influential journals in this field. Alan I. Faden and David J. Loane are recognized as leading contributors. Keyword analysis indicates that neuroinflammation, microglial polarization, and neurodegenerative diseases are pivotal areas for future research.

Conclusion: In recent years, research on TBI-related microglia has proliferated, with current studies primarily focusing on microglial involvement in neuroinflammation, neurodegenerative changes, and microglial polarization following TBI. Since neuroinflammation and neurodegeneration are two hallmark features of TBI, targeting microglia in TBI treatment may become a central focus for future research.

背景:创伤性脑损伤(TBI)是一个严重的全球健康问题,其特点是发病率和死亡率都很高。创伤性脑损伤后的病理和生理变化与小胶质细胞密切相关。小胶质细胞是大脑中的主要免疫细胞,与 TBI 的机制和治疗密切相关。随着该领域研究的不断深入,本研究采用文献计量分析法确定当前研究热点并预测未来趋势:我们决定进行文献计量分析,全面概述与创伤性脑损伤相关的小胶质细胞研究进展。我们旨在为研究人员提供有关当前趋势和未来研究方向的见解:我们从科学网核心数据库中收集了 2000 年至 2023 年间发表的所有与小胶质细胞和创伤性脑损伤相关的文章和综述。我们使用 VOSviewer、CiteSpace 和 R 软件包 "bibliometrix "对这些记录进行了分析:我们检索到来自 25 个国家的 665 篇论文,其中大部分来自美国和中国。有关创伤性脑损伤和小胶质细胞的论文数量每年都在稳步增长。我们的分析显示,《神经创伤杂志》(Journal of Neurotrauma)和《神经炎症杂志》(Journal of Neuroinflammation)是该领域最有影响力的杂志。Alan I. Faden 和 David J. Loane 是公认的主要撰稿人。关键词分析表明,神经炎症、小胶质细胞极化和神经退行性疾病是未来研究的关键领域:近年来,有关创伤性脑损伤相关小胶质细胞的研究激增,目前的研究主要集中在创伤性脑损伤后小胶质细胞参与神经炎症、神经退行性变化和小胶质细胞极化。由于神经炎症和神经退行性变是创伤性脑损伤的两个标志性特征,因此在创伤性脑损伤治疗中以小胶质细胞为靶点可能成为未来研究的核心重点。
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引用次数: 0
Upregulated miR-10b-5p as a potential miRNA signature in amyotrophic lateral sclerosis patients. 肌萎缩性脊髓侧索硬化症患者体内上调的 miR-10b-5p 是一种潜在的 miRNA 标志。
IF 4.2 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-07 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1457704
Banaja P Dash, Axel Freischmidt, Anika M Helferich, Albert C Ludolph, Peter M Andersen, Jochen H Weishaupt, Andreas Hermann

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset disease marked by a progressive degeneration of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. Death in most patients usually occurs within 2-4 years after symptoms onset. Despite promising progress in delineating underlying mechanisms, such as disturbed proteostasis, DNA/RNA metabolism, splicing or proper nucleocytoplasmic shuttling, there are no effective therapies for the vast majority of cases. A reason for this might be the disease heterogeneity and lack of substantial clinical and molecular biomarkers. The identification and validation of such pathophysiology driven biomarkers could be useful for early diagnosis and treatment stratification. Recent advances in next generation RNA-sequencing approaches have provided important insights to identify key changes of non-coding RNAs (ncRNAs) implicated with ALS disease. Especially, microRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression to target several genes/pathways by degrading messenger RNAs (mRNAs) or repressing levels of gene expression. In this study, we expand our previous work to identify top-regulated differentially expressed (DE)-miRNAs by combining different normalizations to search for important and generalisable pathomechanistic dysregulations in ALS as putative novel biomarkers of the disease. For this we performed a consensus pipeline of existing datasets to investigate the transcriptomic profile (mRNAs and miRNAs) of MN cell lines from iPSC-derived SOD1- and TARDBP (TDP-43 protein)-mutant-ALS patients and healthy controls to identify potential signatures and their related pathways associated with neurodegeneration. Transcriptional profiling of miRNA-mRNA interactions from MN cell lines in ALS patients revealed differential expression of genes showed greater vulnerability to KEAP1-NRF2 stress response pathway, sharing a common molecular denominator linked to both disease conditions. We also reported that mutations in above genes led to significant upregulation of the top candidate miR-10b-5p, which we could validate in immortalized lymphoblast cell lines (LCLs) derived from sporadic and familial ALS patients and postmortem tissues of familial ALS patients. Collectively, our findings suggest that miRNA analysis simultaneously performed in various human biological samples may reveal shared miRNA profiles potentially useful as a biomarker of the disease.

肌萎缩性脊髓侧索硬化症(ALS)是一种致命的成人发病性疾病,其特征是脊髓、脑干和运动皮层中的运动神经元(MNs)发生进行性变性。大多数患者通常在发病后 2-4 年内死亡。尽管在研究蛋白质稳态紊乱、DNA/RNA 代谢、剪接或适当的核细胞质穿梭等潜在机制方面取得了令人鼓舞的进展,但绝大多数病例仍没有有效的治疗方法。其中一个原因可能是疾病的异质性以及缺乏实质性的临床和分子生物标志物。鉴定和验证这类病理生理学驱动的生物标志物有助于早期诊断和治疗分层。下一代 RNA 测序方法的最新进展为确定与 ALS 疾病相关的非编码 RNA(ncRNA)的关键变化提供了重要见解。特别是微小 RNA(miRNA)已成为基因表达的关键转录后调控因子,通过降解信使 RNA(mRNA)或抑制基因表达水平来靶向多个基因/通路。在这项研究中,我们扩展了之前的工作,通过结合不同的归一化方法来识别最高调控的差异表达(DE)-miRNA,以寻找 ALS 中重要的、可推广的病理机制失调,作为该疾病的潜在新型生物标志物。为此,我们对现有数据集进行了共识流水线分析,研究了从 iPSC 衍生的 SOD1 和 TARDBP(TDP-43 蛋白)-mutant-ALS 患者和健康对照者的 MN 细胞系的转录组图谱(mRNA 和 miRNA),以确定与神经变性相关的潜在特征及其相关通路。ALS 患者的 MN 细胞系中 miRNA 与 MRNA 相互作用的转录谱分析显示,不同基因的表达更容易受到 KEAP1-NRF2 应激反应通路的影响,这与这两种疾病有共同的分子特征。我们还报告说,上述基因的突变导致了候选的 miR-10b-5p 的显著上调,我们可以在来自散发性和家族性 ALS 患者的永生化淋巴母细胞系(LCLs)以及家族性 ALS 患者的死后组织中验证这一点。总之,我们的研究结果表明,同时对各种人体生物样本进行 miRNA 分析,可能会发现共同的 miRNA 图谱,这些图谱有可能成为该病的生物标志物。
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引用次数: 0
Synaptopodin: a key regulator of Hebbian plasticity. 突触素:希伯来可塑性的关键调节因子
IF 4.2 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-06 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1482844
Pei You Wu, Yanis Inglebert, R Anne McKinney

Synaptopodin, an actin-associated protein found in a subset of dendritic spines in telencephalic neurons, has been described to influence both functional and morphological plasticity under various plasticity paradigms. Synaptopodin is necessary and sufficient for the formation of the spine apparatus, stacks of smooth endoplasmic reticulum cisternae. The spine apparatus is a calcium store that locally regulates calcium dynamics in response to different patterns of activity and is also thought to be a site for local protein synthesis. Synaptopodin is present in ~30% of telencephalic large dendritic spines in vivo and in vitro highlighting the heterogeneous microanatomy and molecular architecture of dendritic spines, an important but not well understood aspect of neuroplasticity. In recent years, it has become increasingly clear that synaptopodin is a formidable regulator of multiple mechanisms essential for learning and memory. In fact, synaptopodin appears to be the decisive factor that determines whether plasticity can occur, acting as a key regulator for synaptic changes. In this review, we summarize the current understanding of synaptopodin's role in various forms of Hebbian synaptic plasticity.

突触素是一种在端脑神经元树突棘亚群中发现的肌动蛋白相关蛋白,据描述,在各种可塑性范式下,突触素对功能和形态可塑性都有影响。突触素是形成脊柱装置--平滑的内质网小室堆叠--的必要和充分条件。脊柱装置是一个钙储存器,可根据不同的活动模式对钙动态进行局部调节,也被认为是局部蛋白质合成的场所。在体内和体外,大约 30% 的端脑大树突棘都存在突触蛋白,这凸显了树突棘的微观解剖学和分子结构的异质性,这是神经可塑性的一个重要方面,但人们对它的了解并不多。近年来,人们越来越清楚地认识到,突触表皮蛋白是学习和记忆所必需的多种机制的强大调节器。事实上,突触素似乎是决定可塑性能否发生的决定性因素,是突触变化的关键调节因子。在这篇综述中,我们总结了目前对突触素在各种形式的希伯来突触可塑性中的作用的理解。
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引用次数: 0
A sexually dimorphic signature of activity-dependent BDNF signaling on the intrinsic excitability of pyramidal neurons in the prefrontal cortex. 前额叶皮层锥体神经元固有兴奋性上依赖于活动的 BDNF 信号的性双态特征。
IF 4.2 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-06 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1496930
Kaijie Ma, Daoqi Zhang, Kylee McDaniel, Maria Webb, Samuel S Newton, Francis S Lee, Luye Qin

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with strong genetic heterogeneity and more prevalent in males than females. We and others hypothesize that diminished activity-dependent neural signaling is a common molecular pathway dysregulated in ASD caused by diverse genetic mutations. Brain-derived neurotrophic factor (BDNF) is a key growth factor mediating activity-dependent neural signaling in the brain. A common single nucleotide polymorphism (SNP) in the pro-domain of the human BDNF gene that leads to a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met) significantly decreases activity-dependent BDNF release without affecting basal BDNF secretion. By using mice with genetic knock-in of this human BDNF methionine (Met) allele, our previous studies have shown differential severity of autism-like social deficits in male and female BDNF+/Met mice. Pyramidal neurons are the principal neurons in the prefrontal cortex (PFC), a key brain region for social behaviors. Here, we investigated the impact of diminished activity-dependent BDNF signaling on the intrinsic excitability of pyramidal neurons in the PFC. Surprisingly, diminished activity-dependent BDNF signaling significantly increased the intrinsic excitability of pyramidal neurons in male mice, but not in female mice. Notably, significantly decreased thresholds of action potentials were observed in male BDNF+/Met mice, but not in female BDNF+/Met mice. Voltage-clamp recordings revealed that the sodium current densities were significantly increased in the pyramidal neurons of male BDNF+/Met mice, which were mediated by increased transcriptional level of Scn2a encoding sodium channel NaV 1.2. Medium after hyperpolarization (mAHP), another important parameter to determine intrinsic neuronal excitability, is strongly associated with neuronal firing frequency. Further, the amplitudes of mAHP were significantly decreased in male BDNF+/Met mice only, which were mediated by the downregulation of Kcnn2 encoding small conductance calcium-activated potassium channel 2 (SK2). This study reveals a sexually dimorphic signature of diminished activity-dependent BDNF signaling on the intrinsic neuronal excitability of pyramidal neurons in the PFC, which provides possible cellular and molecular mechanisms underpinning the sex differences in idiopathic ASD patients and human autism victims who carry BDNF Val66Met SNP.

自闭症谱系障碍(ASD)是一组神经发育障碍,具有很强的遗传异质性,男性发病率高于女性。我们和其他人推测,依赖活动的神经信号传导减弱是自闭症谱系障碍中常见的分子通路,它是由不同的基因突变引起的。脑源性神经营养因子(BDNF)是介导大脑活动依赖性神经信号传导的关键生长因子。人类 BDNF 基因前域的常见单核苷酸多态性(SNP)会导致第 66 个密码子(Val66Met)上的蛋氨酸(Met)取代缬氨酸(Val),从而显著降低活动依赖性 BDNF 的释放,而不影响基础 BDNF 的分泌。通过使用基因敲入人类 BDNF 蛋氨酸(Met)等位基因的小鼠,我们之前的研究表明,雌雄 BDNF+/Met 小鼠的自闭症样社交障碍严重程度不同。锥体神经元是前额叶皮层(PFC)的主要神经元,而前额叶皮层是大脑中社交行为的关键区域。在这里,我们研究了活动依赖性 BDNF 信号减弱对前额叶皮质锥体神经元内在兴奋性的影响。令人惊讶的是,依赖于活动的 BDNF 信号减弱会显著提高雄性小鼠锥体神经元的固有兴奋性,而雌性小鼠则不会。值得注意的是,雄性 BDNF+/Met 小鼠的动作电位阈值明显下降,而雌性 BDNF+/Met 小鼠则没有。电压钳记录显示,雄性 BDNF+/Met 小鼠锥体神经元中的钠离子电流密度明显增加,这是由编码钠离子通道 NaV 1.2 的 Scn2a 的转录水平增加所介导的。超极化后介质(mAHP)是确定神经元内在兴奋性的另一个重要参数,它与神经元的发射频率密切相关。此外,只有雄性BDNF+/Met小鼠的mAHP振幅显著降低,而这是由编码小电导钙激活钾通道2(SK2)的Kcnn2下调介导的。这项研究揭示了活动依赖性BDNF信号对PFC锥体神经元固有神经元兴奋性降低的性别双态特征,为特发性ASD患者和携带BDNF Val66Met SNP的人类自闭症患者的性别差异提供了可能的细胞和分子机制。
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引用次数: 0
Outward depolarization of the microglia mitochondrial membrane potential following lipopolysaccharide exposure: a novel screening tool for microglia metabolomics. 暴露于脂多糖后小胶质细胞线粒体膜电位向外去极化:小胶质细胞代谢组学的新型筛选工具。
IF 4.2 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-06 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1430448
Kendra I McGlothen, Rochelle M Hines, Dustin J Hines

Microglia are non-electrogenic immune cells that respond rapidly to protect the central nervous system (CNS) from infections, injuries, or other forms of damage. Microglia mitochondria are essential for providing the requisite energy resources for immune regulation. While fluctuations in energy metabolism are regulated by mitochondria and are reflected in the mitochondrial membrane potential (ΔΨm), there remains a lack of innovation in microglia-centric tools that capitalize on this. In this study, live imaging of microglia in acute slices from EGFP reporter mice expressing EGFP under the control of the fractalkine receptor (CX3CR1) promoter is combined with loading a fluorescent reporter of ΔΨm. Depolarizations in the ΔΨm were recorded after administering the well-characterized immune stimulant lipopolysaccharide (LPS). Microglia ΔΨm increased in distinctive phases with a relatively steep slope following LPS exposure. Conversely, the ΔΨm of neurons showed minimal regulation, highlighting a distinct microglia ΔΨm response to immune stimuli. Analysis of the depolarization of the microglia ΔΨm in the soma, branches, and endfeet revealed progressive changes in each subcellular domain originating in the soma and progressing outward. The inverse agonist emapunil attenuated the depolarization of the ΔΨm across states in a domain-specific manner. These findings emphasize the contribution of mitochondrial membrane dynamics in regulating microglial responses to immune stimuli. Further, this work advances a novel drug screening strategy for the therapeutic regulation of metabolic activity in inflammatory conditions of the brain.

小胶质细胞是一种非电性免疫细胞,能迅速做出反应,保护中枢神经系统(CNS)免受感染、损伤或其他形式的损害。小胶质细胞线粒体对提供免疫调节所需的能量资源至关重要。虽然能量代谢的波动由线粒体调节,并反映在线粒体膜电位(ΔΨm)中,但以小胶质细胞为中心的工具仍缺乏创新来利用这一点。在这项研究中,结合加载ΔΨm的荧光报告,对在分叉碱受体(CX3CR1)启动子控制下表达EGFP的EGFP报告小鼠急性切片中的小胶质细胞进行了实时成像。在注射特征明显的免疫刺激剂脂多糖(LPS)后记录ΔΨm的去极化。暴露于 LPS 后,小胶质细胞的ΔΨm 以相对陡峭的斜率分阶段增加。与此相反,神经元的ΔΨm却显示出极小的调节作用,突显了小胶质细胞ΔΨm对免疫刺激的独特反应。对小胶质细胞ΔΨm在体节、分支和末梢的去极化分析表明,每个亚细胞域都发生了从体节开始向外的渐进变化。反向激动剂依马普尼以特定领域的方式减弱了不同状态下ΔΨm的去极化。这些发现强调了线粒体膜动力学在调节微神经胶质细胞对免疫刺激的反应中的作用。此外,这项工作还推进了一种新的药物筛选策略,用于治疗调节脑部炎症条件下的代谢活动。
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引用次数: 0
Editorial: Human brain organoids to model neurodegenerative diseases at the BOSS23 Brain Organoid Summer School. 社论:在 BOSS23 脑器官暑期班上,用人脑器官模拟神经退行性疾病。
IF 4.2 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-05 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1501036
Fabio Cavaliere, Dirk M Hermann, Chiara Magliaro
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引用次数: 0
The emerging role of disease-associated microglia in Parkinson's disease. 疾病相关小胶质细胞在帕金森病中的新作用。
IF 4.2 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-05 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1476461
Ritika R Samant, David G Standaert, Ashley S Harms

Disease-associated microglia (DAM) are a subset of microglia that appear at various stages of central nervous system neurodegenerative diseases. DAM were identified using single-cell RNA sequencing within Alzheimer's Disease (AD) where they were characterized by their unique localization near amyloid-β plaques and their phagocytic and lipid-metabolizing features. Unfortunately, activation and etiology of DAM are only understood within the context of AD where Triggering Receptor Expressed On Myeloid Cells 2 (TREM2), a receptor for amyloid-β, appears to be the key regulator in microglial transition to a DAM state. Despite this reliance on TREM2 in AD, DAM appear across other neurodegenerative diseases in which TREM2 may not be a critical player. This begs the question of if DAM are truly the same across all neurodegenerative diseases or if there exists a heterogeneity to DAM across neurodegenerative pathologies. Investigation into this critical gap in the field regarding DAM etiology and activation, as well as DAM function, could be delineated utilizing models of Parkinson's disease (PD) to complement studies in models of AD. Though highly underexplored regarding DAM, PD with its pattern of protein aggregation-associated pathology like AD could serve as the spatiotemporal comparison against AD findings to ascertain the nature of DAM. The experimental vehicle that could guide the future of such investigation is the multi-omics model. With a compound approach focusing on exploring triggers for DAM at the chromatin or mRNA level and related protein output, it becomes possible to strongly characterize and firmly answer the question of what is a DAM.

疾病相关小胶质细胞(DAM)是小胶质细胞的一个亚群,出现在中枢神经系统神经退行性疾病的不同阶段。在阿尔茨海默病(AD)中,通过单细胞 RNA 测序发现了 DAM,其特征是独特地定位在淀粉样β斑块附近,并具有吞噬和脂质代谢功能。遗憾的是,DAM 的激活和病因只有在 AD 的背景下才能被理解,在 AD 的背景下,淀粉样蛋白-β 受体髓系细胞上表达的触发受体 2(TREM2)似乎是小胶质细胞过渡到 DAM 状态的关键调节因子。尽管 AD 依赖于 TREM2,但在其他神经退行性疾病中也出现了 DAM,而 TREM2 在这些疾病中可能不是关键的参与者。这就引出了一个问题:在所有神经退行性疾病中,DAM 是否真的相同,或者在不同的神经退行性疾病中,DAM 是否存在异质性。可以利用帕金森病(PD)模型对这一领域中有关 DAM 病因学和激活以及 DAM 功能的关键空白进行研究,以补充对 AD 模型的研究。尽管对 DAM 的研究非常不足,但帕金森病的蛋白聚集相关病理模式与注意力缺失症类似,可作为与注意力缺失症研究结果的时空对比,以确定 DAM 的性质。多组学模型是指导未来此类研究的实验工具。通过一种复合方法,重点探索染色质或 mRNA 水平上的 DAM 触发因素以及相关的蛋白质输出,就有可能有力地描述和坚定地回答什么是 DAM 的问题。
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引用次数: 0
Magnetic field in the extreme low frequency band protects neuronal and microglia cells from oxygen-glucose deprivation. 极低频段的磁场可保护神经元和小胶质细胞免受氧气-葡萄糖匮乏的影响。
IF 4.2 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1455158
Paloma Mata, Stefano Calovi, Kami Pars Benli, Leyre Iglesias, María Isabel Hernández, Abraham Martín, Alberto Pérez-Samartín, Ander Ramos-Murguialday, María Domercq, Iñaki Ortego-Isasa

Ischemic stroke consists of rapid neural death as a consequence of brain vessel obstruction, followed by damage to the neighboring tissue known as ischemic penumbra. The cerebral tissue in the core of the lesions becomes irreversibly damaged, however, the ischemic penumbra is potentially recoverable during the initial phases after the stroke. Therefore, there is real need for emerging therapeutic strategies to reduce ischemic damage and its spread to the penumbral region. For this reason, we tested the effect of Extreme Low Frequency Electromagnetic Stimulation (ELF-EMS) on in vitro primary neuronal and microglial cultures under oxygen-glucose deprivation (OGD) conditions. ELF-EMS under basal non-OGD conditions did not induce any effect in cell survival. However, ELF-EMS significantly reduced neuronal cell death in OGD conditions and reduced ischemic induced Ca2+ overload. Likewise, ELF-EMS modulated microglia activation and OGD-induced microglia cell death. Hence, this study suggests potential benefits in the application of ELF-EMS to limit ischemic irreversible damages under in vitro stroke conditions, encouraging in vivo preclinical validations of ELF-EMS as a potential therapeutic strategy for ischemic stroke.

缺血性脑卒中是由于脑血管阻塞导致神经迅速死亡,随后邻近组织受损,称为缺血半影。病变核心的脑组织会受到不可逆的损伤,但缺血半影在中风后的最初阶段是可以恢复的。因此,确实需要新的治疗策略来减少缺血性损伤及其向半影区的扩散。为此,我们测试了极低频电磁刺激(ELF-EMS)在氧-葡萄糖剥夺(OGD)条件下对体外原代神经元和小胶质细胞培养物的影响。在基本非缺氧条件下,ELF-EMS 对细胞存活率没有任何影响。然而,ELF-EMS 能显著减少 OGD 条件下神经元细胞的死亡,并降低缺血诱导的 Ca2+ 超载。同样,ELF-EMS 还能调节小胶质细胞的活化和 OGD 诱导的小胶质细胞死亡。因此,这项研究表明,在体外中风条件下,应用ELF-EMS限制缺血性不可逆损伤具有潜在的益处,鼓励将ELF-EMS作为缺血性中风的一种潜在治疗策略进行体内临床前验证。
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引用次数: 0
期刊
Frontiers in Cellular Neuroscience
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