首页 > 最新文献

Glia最新文献

英文 中文
Neuronal and glial cell alterations involved in the retinal degeneration of the familial dysautonomia optic neuropathy 家族性自主神经功能障碍视神经病变视网膜变性所涉及的神经元和神经胶质细胞的改变。
IF 5.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-03 DOI: 10.1002/glia.24612
Anastasia Schultz, Henar Albertos-Arranz, Xavier Sánchez Sáez, Jamie Morgan, Diane C. Darland, Alejandra Gonzalez-Duarte, Horacio Kaufmann, Carlos E. Mendoza-Santiesteban, Nicolás Cuenca, Frances Lefcort

Familial dysautonomia (FD) is a rare genetic neurodevelopmental and neurodegenerative disorder. In addition to the autonomic and peripheral sensory neuropathies that challenge patient survival, one of the most debilitating symptoms affecting patients' quality of life is progressive blindness resulting from the steady loss of retinal ganglion cells (RGCs). Within the FD community, there is a concerted effort to develop treatments to prevent the loss of RGCs. However, the mechanisms underlying the death of RGCs are not well understood. To study the mechanisms underlying RGC death, Pax6-cre;Elp1loxp/loxp male and female mice and postmortem retinal tissue from an FD patient were used to explore the neuronal and non-neuronal cellular pathology associated with the FD optic neuropathy. Neurons, astrocytes, microglia, Müller glia, and endothelial cells were investigated using a combination of histological analyses. We identified a novel disruption of cellular homeostasis and gliosis in the FD retina. Beginning shortly after birth and progressing with age, the FD retina is marked by astrogliosis and perturbations in microglia, which coincide with vascular remodeling. These changes begin before the onset of RGC death, suggesting alterations in the retinal neurovascular unit may contribute to and exacerbate RGC death. We reveal for the first time that the FD retina pathology includes reactive gliosis, increased microglial recruitment to the ganglion cell layer (GCL), disruptions in the deep and superficial vascular plexuses, and alterations in signaling pathways. These studies implicate the neurovascular unit as a disease-modifying target for therapeutic interventions in FD.

家族性自律神经失调症(FD)是一种罕见的遗传性神经发育和神经退行性疾病。除了自主神经和外周感觉神经病变给患者的生存带来挑战外,影响患者生活质量的最令人衰弱的症状之一是视网膜神经节细胞(RGC)的不断丧失导致的渐进性失明。视网膜脱失症患者正在共同努力开发治疗方法,以防止视网膜神经节细胞的丧失。然而,人们对RGC死亡的机制还不甚了解。为了研究RGC死亡的机制,研究人员利用Pax6-cre;Elp1loxp/loxp雄性和雌性小鼠以及一名FD患者的死后视网膜组织来探讨与FD视神经病变相关的神经元和非神经元细胞病理学。我们采用多种组织学分析方法对神经元、星形胶质细胞、小胶质细胞、Müller胶质细胞和内皮细胞进行了研究。我们在 FD 视网膜中发现了一种新的细胞平衡紊乱和胶质增生现象。从出生后不久开始,随着年龄的增长,FD 视网膜出现星形胶质细胞增多和小胶质细胞紊乱,这与血管重塑同时发生。这些变化开始于 RGC 开始死亡之前,表明视网膜神经血管单元的改变可能导致并加剧 RGC 的死亡。我们首次揭示了FD视网膜病理学包括反应性胶质细胞增多、神经节细胞层(GCL)的小胶质细胞招募增加、深层和浅层血管丛的破坏以及信号通路的改变。这些研究表明,神经血管单元是 FD 治疗干预的疾病调节靶点。
{"title":"Neuronal and glial cell alterations involved in the retinal degeneration of the familial dysautonomia optic neuropathy","authors":"Anastasia Schultz,&nbsp;Henar Albertos-Arranz,&nbsp;Xavier Sánchez Sáez,&nbsp;Jamie Morgan,&nbsp;Diane C. Darland,&nbsp;Alejandra Gonzalez-Duarte,&nbsp;Horacio Kaufmann,&nbsp;Carlos E. Mendoza-Santiesteban,&nbsp;Nicolás Cuenca,&nbsp;Frances Lefcort","doi":"10.1002/glia.24612","DOIUrl":"10.1002/glia.24612","url":null,"abstract":"<p>Familial dysautonomia (FD) is a rare genetic neurodevelopmental and neurodegenerative disorder. In addition to the autonomic and peripheral sensory neuropathies that challenge patient survival, one of the most debilitating symptoms affecting patients' quality of life is progressive blindness resulting from the steady loss of retinal ganglion cells (RGCs). Within the FD community, there is a concerted effort to develop treatments to prevent the loss of RGCs. However, the mechanisms underlying the death of RGCs are not well understood. To study the mechanisms underlying RGC death, <i>Pax6-cre;Elp1</i><sup><i>loxp/loxp</i></sup> male and female mice and postmortem retinal tissue from an FD patient were used to explore the neuronal and non-neuronal cellular pathology associated with the FD optic neuropathy. Neurons, astrocytes, microglia, Müller glia, and endothelial cells were investigated using a combination of histological analyses. We identified a novel disruption of cellular homeostasis and gliosis in the FD retina. Beginning shortly after birth and progressing with age, the FD retina is marked by astrogliosis and perturbations in microglia, which coincide with vascular remodeling. These changes begin before the onset of RGC death, suggesting alterations in the retinal neurovascular unit may contribute to and exacerbate RGC death. We reveal for the first time that the FD retina pathology includes reactive gliosis, increased microglial recruitment to the ganglion cell layer (GCL), disruptions in the deep and superficial vascular plexuses, and alterations in signaling pathways. These studies implicate the neurovascular unit as a disease-modifying target for therapeutic interventions in FD.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2268-2294"},"PeriodicalIF":5.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNAJB6 is expressed in neurons and oligodendrocytes of the human brain DNAJB6 在人脑的神经元和少突胶质细胞中表达。
IF 5.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-03 DOI: 10.1002/glia.24615
Jónvá Hentze, Jonas Folke, Susana Aznar, Pia Nyeng, Tomasz Brudek, Christian Hansen

DNAJB6 is a suppressor of α-synuclein aggregation in vivo and in vitro. DNAJB6 is strongly expressed in the brain, and its overall protein expression is altered in neurodegenerative conditions such as Parkinson's Disease (PD) and Multiple System Atrophy (MSA). These two diseases are characterized by accumulation of aggregated α-synuclein in neurons and oligodendrocytes, respectively. To further explore this, we employed post-mortem normal human brain material to investigate the regional and cell type specific protein expression of DNAJB6. We found that the DNAJB6 protein is ubiquitously expressed across various regions of the brain. Notably, we demonstrate for the first time that DNAJB6 is present in nearly half (41%–53%) of the oligodendrocyte population and in the majority (68%–80%) of neurons. However, DNAJB6 was only sparsely present in other cell types such as astrocytes and microglia. Given that α-synuclein aggregation in oligodendrocytes is a hallmark of MSA, we investigated DNAJB6 presence in MSA brains compared to control brains. We found no significant difference in the percentage of oligodendrocytes where DNAJB6 was present in MSA brains relative to control brains. In conclusion, our results reveal an expression of the DNAJB6 protein across various regions of the human brain, and that DNAJB6 is almost exclusively present in neurons and oligodendrocytes. Since prior studies have shown that PD and MSA brains have altered levels of DNAJB6 relative to control brains, DNAJB6 may be an interesting target for drug development.

DNAJB6 是体内和体外α-突触核蛋白聚集的抑制因子。DNAJB6在大脑中的表达量很高,在帕金森病(PD)和多系统萎缩症(MSA)等神经退行性疾病中,DNAJB6的整体蛋白表达量会发生改变。这两种疾病的特征是α-突触核蛋白分别在神经元和少突胶质细胞中聚集。为了进一步探讨这一问题,我们利用死后正常人脑材料研究了 DNAJB6 的区域和细胞类型特异性蛋白表达。我们发现,DNAJB6 蛋白在大脑的各个区域都有普遍表达。值得注意的是,我们首次证明 DNAJB6 存在于近一半(41%-53%)的少突胶质细胞和大多数(68%-80%)的神经元中。然而,DNAJB6 只稀少地存在于其他细胞类型,如星形胶质细胞和小胶质细胞。鉴于少突胶质细胞中的α-突触核蛋白聚集是MSA的特征之一,我们对MSA大脑中DNAJB6的存在情况进行了调查,并与对照组大脑进行了比较。我们发现,与对照组大脑相比,MSA 大脑中 DNAJB6 存在的少突胶质细胞比例没有明显差异。总之,我们的研究结果揭示了 DNAJB6 蛋白在人脑各区域的表达情况,而且 DNAJB6 几乎只存在于神经元和少突胶质细胞中。由于先前的研究表明,相对于对照组大脑,帕金森病和多发性硬化症患者大脑中的 DNAJB6 水平发生了改变,因此 DNAJB6 可能是一个有趣的药物开发靶点。
{"title":"DNAJB6 is expressed in neurons and oligodendrocytes of the human brain","authors":"Jónvá Hentze,&nbsp;Jonas Folke,&nbsp;Susana Aznar,&nbsp;Pia Nyeng,&nbsp;Tomasz Brudek,&nbsp;Christian Hansen","doi":"10.1002/glia.24615","DOIUrl":"10.1002/glia.24615","url":null,"abstract":"<p>DNAJB6 is a suppressor of α-synuclein aggregation <i>in vivo</i> and <i>in vitro</i>. DNAJB6 is strongly expressed in the brain, and its overall protein expression is altered in neurodegenerative conditions such as Parkinson's Disease (PD) and Multiple System Atrophy (MSA). These two diseases are characterized by accumulation of aggregated α-synuclein in neurons and oligodendrocytes, respectively. To further explore this, we employed <i>post-mortem</i> normal human brain material to investigate the regional and cell type specific protein expression of DNAJB6. We found that the DNAJB6 protein is ubiquitously expressed across various regions of the brain. Notably, we demonstrate for the first time that DNAJB6 is present in nearly half (41%–53%) of the oligodendrocyte population and in the majority (68%–80%) of neurons. However, DNAJB6 was only sparsely present in other cell types such as astrocytes and microglia. Given that α-synuclein aggregation in oligodendrocytes is a hallmark of MSA, we investigated DNAJB6 presence in MSA brains compared to control brains. We found no significant difference in the percentage of oligodendrocytes where DNAJB6 was present in MSA brains relative to control brains. In conclusion, our results reveal an expression of the DNAJB6 protein across various regions of the human brain, and that DNAJB6 is almost exclusively present in neurons and oligodendrocytes. Since prior studies have shown that PD and MSA brains have altered levels of DNAJB6 relative to control brains, DNAJB6 may be an interesting target for drug development.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2313-2326"},"PeriodicalIF":5.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Loss of prohibitin 2 in Schwann cells dysregulates key transcription factors controlling developmental myelination 许旺细胞中 prohibitin 2 的缺失会导致控制髓鞘发育的关键转录因子失调。
IF 5.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-31 DOI: 10.1002/glia.24610
Emma R. Wilson, Gustavo Della-Flora Nunes, Shichen Shen, Seth Moore, Joseph Gawron, Jessica Maxwell, Umair Syed, Edward Hurley, Meghana Lanka, Jun Qu, Laurent Désaubry, Lawrence Wrabetz, Yannick Poitelon, M. Laura Feltri

Schwann cells are critical for the proper development and function of the peripheral nervous system (PNS), where they form a collaborative relationship with axons. Past studies highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this, showing that drug-mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (Phb2) in vivo results in severe defects in radial sorting and myelination. We show in vivo that Phb2-null Schwann cells cannot effectively proliferate and the transcription factors EGR2 (KROX20), POU3F1 (OCT6), and POU3F2 (BRN2), necessary for proper Schwann cell maturation, are dysregulated. Schwann cell-specific deletion of Jun, a transcription factor associated with negative regulation of myelination, confers partial rescue of the developmental defect seen in mice lacking Schwann cell Phb2. Finally, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on neuronal signals, and thus are potential mediators of PHB2-associated developmental defects. This work develops our understanding of Schwann cell biology, revealing that Phb2 may modulate the timely expression of transcription factors necessary for proper PNS development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell.

许旺细胞对周围神经系统(PNS)的正常发育和功能至关重要,它们与轴突形成了协作关系。过去的研究突出表明,一对名为抑制蛋白的蛋白质在许旺细胞生物学中发挥着重要作用。抑制蛋白是一种普遍表达的多功能蛋白质。我们以前的研究表明,抑制蛋白在许旺细胞线粒体中对髓鞘的长期维持和轴突的健康起着至关重要的作用,但它们也可能在发育过程中存在于许旺细胞-轴突界面。在这里,我们进一步说明了这一点,表明药物介导的体外禁止素调节会破坏髓鞘化,并证实体内许旺细胞特异性消减禁止素 2 (Phb2) 会导致径向分选和髓鞘化的严重缺陷。我们在体内发现,Phab2缺失的许旺细胞不能有效增殖,而且适当的许旺细胞成熟所必需的转录因子EGR2 (KROX20)、POU3F1 (OCT6)和POU3F2 (BRN2)失调。Jun是一种与髓鞘化负调控相关的转录因子,它的舍旺细胞特异性缺失可部分挽救缺乏舍旺细胞Phb2的小鼠的发育缺陷。最后,我们确定了一组候选 PHB2 相互作用因子,它们会根据神经元信号改变与 PHB2 的相互作用,因此是 PHB2 相关发育缺陷的潜在介导因子。这项工作加深了我们对许旺细胞生物学的理解,揭示了PHB2可能会调节正常PNS发育所必需的转录因子的及时表达,并提出了可能在PHB2介导的轴突信号在许旺细胞中的整合中发挥作用的候选因子。
{"title":"Loss of prohibitin 2 in Schwann cells dysregulates key transcription factors controlling developmental myelination","authors":"Emma R. Wilson,&nbsp;Gustavo Della-Flora Nunes,&nbsp;Shichen Shen,&nbsp;Seth Moore,&nbsp;Joseph Gawron,&nbsp;Jessica Maxwell,&nbsp;Umair Syed,&nbsp;Edward Hurley,&nbsp;Meghana Lanka,&nbsp;Jun Qu,&nbsp;Laurent Désaubry,&nbsp;Lawrence Wrabetz,&nbsp;Yannick Poitelon,&nbsp;M. Laura Feltri","doi":"10.1002/glia.24610","DOIUrl":"10.1002/glia.24610","url":null,"abstract":"<p>Schwann cells are critical for the proper development and function of the peripheral nervous system (PNS), where they form a collaborative relationship with axons. Past studies highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this, showing that drug-mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (<i>Phb2</i>) in vivo results in severe defects in radial sorting and myelination. We show in vivo that <i>Phb2</i>-null Schwann cells cannot effectively proliferate and the transcription factors EGR2 (KROX20), POU3F1 (OCT6), and POU3F2 (BRN2), necessary for proper Schwann cell maturation, are dysregulated. Schwann cell-specific deletion of <i>Jun</i>, a transcription factor associated with negative regulation of myelination, confers partial rescue of the developmental defect seen in mice lacking Schwann cell <i>Phb2</i>. Finally, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on neuronal signals, and thus are potential mediators of PHB2-associated developmental defects. This work develops our understanding of Schwann cell biology, revealing that <i>Phb2</i> may modulate the timely expression of transcription factors necessary for proper PNS development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2247-2267"},"PeriodicalIF":5.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Astrocytic Ca2+ activation by chemogenetics mitigates the effect of kainic acid-induced excitotoxicity on the hippocampus 通过化学遗传学激活星形胶质细胞 Ca2+ 可减轻凯尼酸诱导的兴奋性毒性对海马的影响。
IF 5.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-26 DOI: 10.1002/glia.24607
Nira Hernández-Martín, María Gómez Martínez, Pablo Bascuñana, Rubén Fernández de la Rosa, Luis García-García, Francisca Gómez, Maite Solas, Eduardo D. Martín, Miguel A. Pozo

Astrocytes play a multifaceted role regulating brain glucose metabolism, ion homeostasis, neurotransmitters clearance, and water dynamics being essential in supporting synaptic function. Under different pathological conditions such as brain stroke, epilepsy, and neurodegenerative disorders, excitotoxicity plays a crucial role, however, the contribution of astrocytic activity in protecting neurons from excitotoxicity-induced damage is yet to be fully understood. In this work, we evaluated the effect of astrocytic activation by Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on brain glucose metabolism in wild-type (WT) mice, and we investigated the effects of sustained astrocyte activation following an insult induced by intrahippocampal (iHPC) kainic acid (KA) injection using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging, along with behavioral test, nuclear magnetic resonance (NMR) spectroscopy and histochemistry. Astrocytic Ca2+ activation increased the 18F-FDG uptake, but this effect was not found when the study was performed in knock out mice for type-2 inositol 1,4,5-trisphosphate receptor (Ip3r2−/−) nor in floxed mice to abolish glucose transporter 1 (GLUT1) expression in hippocampal astrocytes (GLUT1ΔGFAP). Sustained astrocyte activation after KA injection reversed the brain glucose hypometabolism, restored hippocampal function, prevented neuronal death, and increased hippocampal GABA levels. The findings of our study indicate that astrocytic GLUT1 function is crucial for regulating brain glucose metabolism. Astrocytic Ca2+ activation has been shown to promote adaptive changes that significantly contribute to mitigating the effects of KA-induced damage. This evidence suggests a protective role of activated astrocytes against KA-induced excitotoxicity.

星形胶质细胞在调节大脑葡萄糖代谢、离子平衡、神经递质清除和水动力学等方面发挥着多方面的作用,对支持突触功能至关重要。在脑卒中、癫痫和神经退行性疾病等不同病理情况下,兴奋性毒性起着至关重要的作用,然而,星形胶质细胞的活性在保护神经元免受兴奋性毒性诱导的损伤方面所起的作用尚未完全清楚。在这项工作中,我们评估了通过设计药物独家激活的设计受体(DREADDs)激活星形胶质细胞对野生型(WT)小鼠脑葡萄糖代谢的影响、我们使用 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) 正电子发射断层扫描 (PET) 成像、行为测试、核磁共振 (NMR) 光谱和组织化学方法研究了海马内注射凯尼酸 (KA) 引起的损伤后星形胶质细胞持续激活的影响。星形胶质细胞的 Ca2+ 激活增加了 18F-FDG 摄取量,但在敲除 2 型肌醇 1,4,5- 三磷酸受体(Ip3r2-/-)的小鼠和在海马星形胶质细胞葡萄糖转运体 1(GLUT1)表达缺失(GLUT1ΔGFAP)的小鼠中进行的研究却没有发现这种效应。注射 KA 后,星形胶质细胞的持续激活逆转了脑葡萄糖低代谢,恢复了海马功能,防止了神经元死亡,并增加了海马 GABA 水平。我们的研究结果表明,星形胶质细胞的 GLUT1 功能对调节大脑葡萄糖代谢至关重要。已证明星形胶质细胞 Ca2+ 激活可促进适应性变化,从而大大有助于减轻 KA 诱导的损伤。这些证据表明,活化的星形胶质细胞对 KA 诱导的兴奋毒性具有保护作用。
{"title":"Astrocytic Ca2+ activation by chemogenetics mitigates the effect of kainic acid-induced excitotoxicity on the hippocampus","authors":"Nira Hernández-Martín,&nbsp;María Gómez Martínez,&nbsp;Pablo Bascuñana,&nbsp;Rubén Fernández de la Rosa,&nbsp;Luis García-García,&nbsp;Francisca Gómez,&nbsp;Maite Solas,&nbsp;Eduardo D. Martín,&nbsp;Miguel A. Pozo","doi":"10.1002/glia.24607","DOIUrl":"10.1002/glia.24607","url":null,"abstract":"<p>Astrocytes play a multifaceted role regulating brain glucose metabolism, ion homeostasis, neurotransmitters clearance, and water dynamics being essential in supporting synaptic function. Under different pathological conditions such as brain stroke, epilepsy, and neurodegenerative disorders, excitotoxicity plays a crucial role, however, the contribution of astrocytic activity in protecting neurons from excitotoxicity-induced damage is yet to be fully understood. In this work, we evaluated the effect of astrocytic activation by Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on brain glucose metabolism in wild-type (WT) mice, and we investigated the effects of sustained astrocyte activation following an insult induced by intrahippocampal (iHPC) kainic acid (KA) injection using 2-deoxy-2-[<sup>18</sup>F]-fluoro-D-glucose (<sup>18</sup>F-FDG) positron emission tomography (PET) imaging, along with behavioral test, nuclear magnetic resonance (NMR) spectroscopy and histochemistry. Astrocytic Ca<sup>2+</sup> activation increased the <sup>18</sup>F-FDG uptake, but this effect was not found when the study was performed in <i>knock out</i> mice for type-2 inositol 1,4,5-trisphosphate receptor (Ip3r2<sup>−/−</sup>) nor in <i>floxed</i> mice to abolish glucose transporter 1 (GLUT1) expression in hippocampal astrocytes (GLUT1<sup>ΔGFAP</sup>). Sustained astrocyte activation after KA injection reversed the brain glucose hypometabolism, restored hippocampal function, prevented neuronal death, and increased hippocampal GABA levels. The findings of our study indicate that astrocytic GLUT1 function is crucial for regulating brain glucose metabolism. Astrocytic Ca<sup>2+</sup> activation has been shown to promote adaptive changes that significantly contribute to mitigating the effects of KA-induced damage. This evidence suggests a protective role of activated astrocytes against KA-induced excitotoxicity.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2217-2230"},"PeriodicalIF":5.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endothelin-1 increases Na+-K+-2Cl− cotransporter-1 expression in cultured astrocytes and in traumatic brain injury model: An involvement of HIF1α activation 内皮素-1 可增加培养的星形胶质细胞和创伤性脑损伤模型中 Na+-K+-2Cl- 共转运体-1 的表达:HIF1α 激活的参与。
IF 5.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-21 DOI: 10.1002/glia.24609
Yutaka Koyama, Yasuhiro Hamada, Yura Fukui, Nami Hosogi, Rina Fujimoto, Shigeru Hishinuma, Yasuhiro Ogawa, Kenta Takahashi, Yasuhiko Izumi, Shotaro Michinaga

Na+-K+-2Cl cotransporter-1 (NKCC1) is present in brain cells, including astrocytes. The expression of astrocytic NKCC1 increases in the acute phase of traumatic brain injury (TBI), which induces brain edema. Endothelin-1 (ET-1) is a factor that induces brain edema and regulates the expression of several pathology-related genes in astrocytes. In the present study, we investigated the effect of ET-1 on NKCC1 expression in astrocytes. ET-1 (100 nM)-treated cultured astrocytes showed increased NKCC1 mRNA and protein levels. The effect of ET-1 on NKCC1 expression in cultured astrocytes was reduced by BQ788 (1 μM), an ETB antagonist, but not by FR139317 (1 μM), an ETA antagonist. The involvement of ET-1 in NKCC1 expression in TBI was examined using a fluid percussion injury (FPI) mouse model that replicates the pathology of TBI with high reproducibility. Administration of BQ788 (15 nmol/day) decreased FPI-induced expressions of NKCC1 mRNA and protein, accompanied with a reduction of astrocytic activation. FPI-induced brain edema was attenuated by BQ788 and NKCC1 inhibitors (azosemide and bumetanide). ET-1-treated cultured astrocytes showed increased mRNA and protein expression of hypoxia-inducible factor-1α (HIF1α). Immunohistochemical observations of mouse cerebrum after FPI showed co-localization of HIF1α with GFAP-positive astrocytes. Increased HIF1α expression in the TBI model was reversed by BQ788. FM19G11 (an HIF inhibitor, 1 μM) and HIF1α siRNA suppressed ET-induced increase in NKCC1 expression in cultured astrocytes. These results indicate that ET-1 increases NKCC1 expression in astrocytes through the activation of HIF1α.

Na+-K+-2Cl- 共转运体-1(NKCC1)存在于包括星形胶质细胞在内的脑细胞中。在诱发脑水肿的创伤性脑损伤(TBI)急性期,星形胶质细胞 NKCC1 的表达会增加。内皮素-1(ET-1)是一种诱导脑水肿的因子,可调节星形胶质细胞中多个病理相关基因的表达。在本研究中,我们研究了 ET-1 对星形胶质细胞中 NKCC1 表达的影响。ET-1(100 nM)处理培养的星形胶质细胞显示 NKCC1 mRNA 和蛋白水平升高。ET-1 对培养的星形胶质细胞中 NKCC1 表达的影响会被 ETB 拮抗剂 BQ788(1 μM)降低,但不会被 ETA 拮抗剂 FR139317(1 μM)降低。我们使用一种液体叩击伤(FPI)小鼠模型研究了 ET-1 在创伤性脑损伤中参与 NKCC1 表达的情况。服用 BQ788(15 毫摩尔/天)可降低 FPI 诱导的 NKCC1 mRNA 和蛋白表达,同时减少星形胶质细胞的活化。BQ788 和 NKCC1 抑制剂(阿佐塞米和布美他尼)可减轻 FPI 引起的脑水肿。经 ET-1 处理的培养星形胶质细胞显示缺氧诱导因子-1α(HIF1α)的 mRNA 和蛋白表达增加。对 FPI 后小鼠大脑的免疫组化观察显示,HIF1α 与 GFAP 阳性星形胶质细胞共定位。BQ788 逆转了创伤性脑损伤模型中 HIF1α 表达的增加。FM19G11(一种 HIF 抑制剂,1 μM)和 HIF1α siRNA 抑制了 ET 诱导的培养星形胶质细胞中 NKCC1 表达的增加。这些结果表明,ET-1 可通过激活 HIF1α 增加星形胶质细胞中 NKCC1 的表达。
{"title":"Endothelin-1 increases Na+-K+-2Cl− cotransporter-1 expression in cultured astrocytes and in traumatic brain injury model: An involvement of HIF1α activation","authors":"Yutaka Koyama,&nbsp;Yasuhiro Hamada,&nbsp;Yura Fukui,&nbsp;Nami Hosogi,&nbsp;Rina Fujimoto,&nbsp;Shigeru Hishinuma,&nbsp;Yasuhiro Ogawa,&nbsp;Kenta Takahashi,&nbsp;Yasuhiko Izumi,&nbsp;Shotaro Michinaga","doi":"10.1002/glia.24609","DOIUrl":"10.1002/glia.24609","url":null,"abstract":"<p>Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>−</sup> cotransporter-1 (NKCC1) is present in brain cells, including astrocytes. The expression of astrocytic NKCC1 increases in the acute phase of traumatic brain injury (TBI), which induces brain edema. Endothelin-1 (ET-1) is a factor that induces brain edema and regulates the expression of several pathology-related genes in astrocytes. In the present study, we investigated the effect of ET-1 on NKCC1 expression in astrocytes. ET-1 (100 nM)-treated cultured astrocytes showed increased NKCC1 mRNA and protein levels. The effect of ET-1 on NKCC1 expression in cultured astrocytes was reduced by BQ788 (1 μM), an ET<sub>B</sub> antagonist, but not by FR139317 (1 μM), an ET<sub>A</sub> antagonist. The involvement of ET-1 in NKCC1 expression in TBI was examined using a fluid percussion injury (FPI) mouse model that replicates the pathology of TBI with high reproducibility. Administration of BQ788 (15 nmol/day) decreased FPI-induced expressions of NKCC1 mRNA and protein, accompanied with a reduction of astrocytic activation. FPI-induced brain edema was attenuated by BQ788 and NKCC1 inhibitors (azosemide and bumetanide). ET-1-treated cultured astrocytes showed increased mRNA and protein expression of hypoxia-inducible factor-1α (HIF1α). Immunohistochemical observations of mouse cerebrum after FPI showed co-localization of HIF1α with GFAP-positive astrocytes. Increased HIF1α expression in the TBI model was reversed by BQ788. FM19G11 (an HIF inhibitor, 1 μM) and HIF1α siRNA suppressed ET-induced increase in NKCC1 expression in cultured astrocytes. These results indicate that ET-1 increases NKCC1 expression in astrocytes through the activation of HIF1α.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2231-2246"},"PeriodicalIF":5.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Identification of astrocyte-like cells in an adult ascidian during regeneration of the central nervous system 在中枢神经系统再生过程中鉴定出一种成年蛔虫体内的星形胶质细胞。
IF 5.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-17 DOI: 10.1002/glia.24605
Bianca Nicole Santos Paes Medina, Taynan Motta Portal, Carlos Augusto Borges de Andrade Gomes, Rodrigo Nunes-da-Fonseca, Silvana Allodi, Cintia Monteiro-de-Barros

The mechanisms underlying regeneration of the central nervous system (CNS) following lesions have been studied extensively in both vertebrate and invertebrate models. To shed light on regeneration, ascidians, a sister group of vertebrates and with remarkable ability to regenerate their brains, constitute an appropriate model system. Glial cells have been implicated in regeneration in vertebrates; however, their role in the adult ascidian CNS regeneration is unknown. A model of degeneration and regeneration using the neurotoxin 3-acetylpyridine (3AP) in the brain of the ascidian Styela plicata was used to identify astrocyte-like cells and investigate their role. We studied the CNS of control ascidians (injected with artificial sea water) and of ascidians whose CNS was regenerating (1 and 10 days after the injection with 3AP). Our results show that the mRNA of the ortholog of glutamine synthetase (GS), a glial-cell marker in vertebrates, is increased during the early stages of regeneration. Confirming the identity of GS, the protein was identified via immunostaining in a cell population during the same regeneration stage. Last, a single ortholog of GS (GSII) is present in ascidian and amphioxus genomes, while two types exist in fungi, some invertebrates, and vertebrates, suggesting that ascidians have lost the GSI type. Taken together, our findings revealed that a cell population expressing glial-cell markers may play a role in regeneration in adult ascidians. This is the first report of astrocyte-like cells in the adult ascidian CNS, and contributes to understanding of the evolution of glial cells among metazoans.

人们在脊椎动物和无脊椎动物模型中广泛研究了中枢神经系统(CNS)受损后的再生机制。腹足类是脊椎动物的姊妹类,具有显著的大脑再生能力,是研究再生的合适模型系统。神经胶质细胞与脊椎动物的再生有关,但它们在成年腹足类中枢神经系统再生中的作用尚不清楚。我们使用神经毒素 3-乙酰基吡啶(3AP)在腹甲鱼类 Styela plicata 的大脑中建立了一个退化和再生模型,以确定类星形胶质细胞并研究它们的作用。我们研究了对照组(注射人工海水)和中枢神经系统正在再生(注射 3AP 1 天和 10 天后)的腹水生物的中枢神经系统。我们的研究结果表明,谷氨酰胺合成酶(GS)的同源物(脊椎动物神经胶质细胞的标志物)的 mRNA 在再生的早期阶段有所增加。为了证实谷氨酰胺合成酶的身份,我们通过免疫染色在同一再生阶段的细胞群中鉴定出了谷氨酰胺合成酶蛋白。最后,在腹足类和文昌鱼的基因组中存在单一的GS直向同源物(GSII),而在真菌、一些无脊椎动物和脊椎动物中存在两种类型,这表明腹足类已经失去了GSI类型。总之,我们的研究结果表明,表达神经胶质细胞标记的细胞群可能在成年腹足类的再生过程中发挥作用。这是首次报道在成年腹足类的中枢神经系统中发现类似星形胶质细胞的细胞,有助于了解胶质细胞在后生动物中的进化。
{"title":"Identification of astrocyte-like cells in an adult ascidian during regeneration of the central nervous system","authors":"Bianca Nicole Santos Paes Medina,&nbsp;Taynan Motta Portal,&nbsp;Carlos Augusto Borges de Andrade Gomes,&nbsp;Rodrigo Nunes-da-Fonseca,&nbsp;Silvana Allodi,&nbsp;Cintia Monteiro-de-Barros","doi":"10.1002/glia.24605","DOIUrl":"10.1002/glia.24605","url":null,"abstract":"<p>The mechanisms underlying regeneration of the central nervous system (CNS) following lesions have been studied extensively in both vertebrate and invertebrate models. To shed light on regeneration, ascidians, a sister group of vertebrates and with remarkable ability to regenerate their brains, constitute an appropriate model system. Glial cells have been implicated in regeneration in vertebrates; however, their role in the adult ascidian CNS regeneration is unknown. A model of degeneration and regeneration using the neurotoxin 3-acetylpyridine (3AP) in the brain of the ascidian <i>Styela plicata</i> was used to identify astrocyte-like cells and investigate their role. We studied the CNS of control ascidians (injected with artificial sea water) and of ascidians whose CNS was regenerating (1 and 10 days after the injection with 3AP). Our results show that the mRNA of the ortholog of glutamine synthetase (GS), a glial-cell marker in vertebrates, is increased during the early stages of regeneration. Confirming the identity of GS, the protein was identified via immunostaining in a cell population during the same regeneration stage. Last, a single ortholog of GS (GSII) is present in ascidian and amphioxus genomes, while two types exist in fungi, some invertebrates, and vertebrates, suggesting that ascidians have lost the GSI type. Taken together, our findings revealed that a cell population expressing glial-cell markers may play a role in regeneration in adult ascidians. This is the first report of astrocyte-like cells in the adult ascidian CNS, and contributes to understanding of the evolution of glial cells among metazoans.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2190-2200"},"PeriodicalIF":5.4,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Schwann cell JUN expression worsens motor performance in an amyotrophic lateral sclerosis mouse model 在肌萎缩性脊髓侧索硬化症小鼠模型中,许旺细胞 JUN 的表达会使运动能力下降。
IF 5.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-16 DOI: 10.1002/glia.24604
Sonia Cabeza-Fernández, Rubí Hernández-Rojas, Angeles Casillas-Bajo, Nikiben Patel, Alerie G. de la Fuente, Hugo Cabedo, Jose A. Gomez-Sanchez

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by motor neuron death and distal axonopathy. Despite its clinical severity and profound impact in the patients and their families, many questions about its pathogenesis remain still unclear, including the role of Schwann cells and axon-glial signaling in disease progression. Upon axonal injury, upregulation of JUN transcription factor promotes Schwann cell reprogramming into a repair phenotype that favors axon regrowth and neuronal survival. To study the potential role of repair Schwann cells on motoneuron survival in amyotrophic lateral sclerosis, we generated a mouse line that over-expresses JUN in the Schwann cells of the SOD1G93A mutant, a mouse model of this disease. Then, we explored disease progression by evaluating survival, motor performance and histology of peripheral nerves and spinal cord of these mice. We found that Schwann cell JUN overexpression does not prevent axon degeneration neither motor neuron death in the SOD1G93A mice. Instead, it induces a partial demyelination of medium and large size axons, worsening motor performance and resulting in more aggressive disease phenotype.

肌萎缩侧索硬化症是一种以运动神经元死亡和远端轴突病变为特征的破坏性神经退行性疾病。尽管该病临床症状严重,对患者及其家庭影响深远,但有关其发病机制的许多问题仍不清楚,包括许旺细胞和轴突胶质细胞信号传导在疾病进展中的作用。轴突损伤后,JUN转录因子的上调会促进许旺细胞重编程为修复表型,从而有利于轴突再生和神经元存活。为了研究肌萎缩性脊髓侧索硬化症中修复许旺细胞对运动神经元存活的潜在作用,我们生成了一个小鼠品系,在该病的小鼠模型 SOD1G93A 突变体的许旺细胞中过度表达 JUN。然后,我们通过评估这些小鼠的存活率、运动表现以及外周神经和脊髓组织学来探索疾病的进展。我们发现,SOD1G93A 小鼠过表达许旺细胞 JUN 既不能防止轴突变性,也不能防止运动神经元死亡。相反,它会诱导中型和大型轴突的部分脱髓鞘,使运动表现恶化,并导致更具侵袭性的疾病表型。
{"title":"Schwann cell JUN expression worsens motor performance in an amyotrophic lateral sclerosis mouse model","authors":"Sonia Cabeza-Fernández,&nbsp;Rubí Hernández-Rojas,&nbsp;Angeles Casillas-Bajo,&nbsp;Nikiben Patel,&nbsp;Alerie G. de la Fuente,&nbsp;Hugo Cabedo,&nbsp;Jose A. Gomez-Sanchez","doi":"10.1002/glia.24604","DOIUrl":"10.1002/glia.24604","url":null,"abstract":"<p>Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by motor neuron death and distal axonopathy. Despite its clinical severity and profound impact in the patients and their families, many questions about its pathogenesis remain still unclear, including the role of Schwann cells and axon-glial signaling in disease progression. Upon axonal injury, upregulation of JUN transcription factor promotes Schwann cell reprogramming into a repair phenotype that favors axon regrowth and neuronal survival. To study the potential role of repair Schwann cells on motoneuron survival in amyotrophic lateral sclerosis, we generated a mouse line that over-expresses JUN in the Schwann cells of the SOD1<sup>G93A</sup> mutant, a mouse model of this disease. Then, we explored disease progression by evaluating survival, motor performance and histology of peripheral nerves and spinal cord of these mice. We found that Schwann cell JUN overexpression does not prevent axon degeneration neither motor neuron death in the SOD1<sup>G93A</sup> mice. Instead, it induces a partial demyelination of medium and large size axons, worsening motor performance and resulting in more aggressive disease phenotype.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2178-2189"},"PeriodicalIF":5.4,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24604","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Memoriam: Arne Schousboe 1944–2024 悼念Arne Schousboe 1944-2024.
IF 5.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-15 DOI: 10.1002/glia.24608
Jens V. Andersen, Helle S. Waagepetersen, Lasse K. Bak
{"title":"In Memoriam: Arne Schousboe 1944–2024","authors":"Jens V. Andersen,&nbsp;Helle S. Waagepetersen,&nbsp;Lasse K. Bak","doi":"10.1002/glia.24608","DOIUrl":"10.1002/glia.24608","url":null,"abstract":"","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2357-2359"},"PeriodicalIF":5.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Astrocytic centrin-2 expression in entorhinal cortex correlates with Alzheimer's disease severity 内叶皮层中星形胶质细胞中心蛋白-2的表达与阿尔茨海默病的严重程度有关。
IF 5.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-15 DOI: 10.1002/glia.24603
Elisa Degl'Innocenti, Tino Emanuele Poloni, Valentina Medici, Francesco Olimpico, Francesco Finamore, Xhulja Profka, Karouna Bascarane, Castrese Morrone, Aldo Pastore, Carole Escartin, Liam A. McDonnell, Maria Teresa Dell'Anno

Astrogliosis is a condition shared by acute and chronic neurological diseases and includes morphological, proteomic, and functional rearrangements of astroglia. In Alzheimer's disease (AD), reactive astrocytes frame amyloid deposits and exhibit structural changes associated with the overexpression of specific proteins, mostly belonging to intermediate filaments. At a functional level, amyloid beta triggers dysfunctional calcium signaling in astrocytes, which contributes to the maintenance of chronic neuroinflammation. Therefore, the identification of intracellular players that participate in astrocyte calcium signaling can help unveil the mechanisms underlying astrocyte reactivity and loss of function in AD. We have recently identified the calcium-binding protein centrin-2 (CETN2) as a novel astrocyte marker in the human brain and, in order to determine whether astrocytic CETN2 expression and distribution could be affected by neurodegenerative conditions, we examined its pattern in control and sporadic AD patients. By immunoblot, immunohistochemistry, and targeted-mass spectrometry, we report a positive correlation between entorhinal CETN2 immunoreactivity and neurocognitive impairment, along with the abundance of amyloid depositions and neurofibrillary tangles, thus highlighting a linear relationship between CETN2 expression and AD progression. CETN2-positive astrocytes were dispersed in the entorhinal cortex with a clustered pattern and colocalized with reactive glia markers STAT3, NFATc3, and YKL-40, indicating a human-specific role in AD-induced astrogliosis. Collectively, our data provide the first evidence that CETN2 is part of the astrocytic calcium toolkit undergoing rearrangements in AD and adds CETN2 to the list of proteins that could play a role in disease evolution.

星形胶质细胞增多症是急性和慢性神经系统疾病的共同症状,包括星形胶质细胞的形态学、蛋白质组和功能重排。在阿尔茨海默病(AD)中,反应性星形胶质细胞会形成淀粉样沉积物,并表现出与特定蛋白质(大多属于中间丝)过度表达相关的结构变化。在功能层面上,淀粉样蛋白 beta 会引发星形胶质细胞中的钙信号功能失调,从而导致慢性神经炎症的维持。因此,鉴定参与星形胶质细胞钙信号转导的细胞内参与者有助于揭示AD中星形胶质细胞反应性和功能丧失的内在机制。为了确定星形胶质细胞 CETN2 的表达和分布是否会受到神经退行性疾病的影响,我们研究了其在对照组和散发性 AD 患者中的表达模式。通过免疫印迹、免疫组织化学和靶向质谱分析,我们发现内侧星形胶质细胞 CETN2 免疫活性与神经认知功能障碍以及淀粉样沉积和神经纤维缠结的丰度呈正相关,从而凸显了 CETN2 表达与 AD 进展之间的线性关系。CETN2阳性星形胶质细胞以聚集模式分散在内侧皮层,并与反应性胶质细胞标记物STAT3、NFATc3和YKL-40共聚焦,表明其在AD诱导的星形胶质细胞增生中具有人类特异性作用。总之,我们的数据首次证明了 CETN2 是 AD 中发生重排的星形胶质细胞钙工具箱的一部分,并将 CETN2 加入了可能在疾病演变中发挥作用的蛋白质列表。
{"title":"Astrocytic centrin-2 expression in entorhinal cortex correlates with Alzheimer's disease severity","authors":"Elisa Degl'Innocenti,&nbsp;Tino Emanuele Poloni,&nbsp;Valentina Medici,&nbsp;Francesco Olimpico,&nbsp;Francesco Finamore,&nbsp;Xhulja Profka,&nbsp;Karouna Bascarane,&nbsp;Castrese Morrone,&nbsp;Aldo Pastore,&nbsp;Carole Escartin,&nbsp;Liam A. McDonnell,&nbsp;Maria Teresa Dell'Anno","doi":"10.1002/glia.24603","DOIUrl":"10.1002/glia.24603","url":null,"abstract":"<p>Astrogliosis is a condition shared by acute and chronic neurological diseases and includes morphological, proteomic, and functional rearrangements of astroglia. In Alzheimer's disease (AD), reactive astrocytes frame amyloid deposits and exhibit structural changes associated with the overexpression of specific proteins, mostly belonging to intermediate filaments. At a functional level, amyloid beta triggers dysfunctional calcium signaling in astrocytes, which contributes to the maintenance of chronic neuroinflammation. Therefore, the identification of intracellular players that participate in astrocyte calcium signaling can help unveil the mechanisms underlying astrocyte reactivity and loss of function in AD. We have recently identified the calcium-binding protein centrin-2 (CETN2) as a novel astrocyte marker in the human brain and, in order to determine whether astrocytic CETN2 expression and distribution could be affected by neurodegenerative conditions, we examined its pattern in control and sporadic AD patients. By immunoblot, immunohistochemistry, and targeted-mass spectrometry, we report a positive correlation between entorhinal CETN2 immunoreactivity and neurocognitive impairment, along with the abundance of amyloid depositions and neurofibrillary tangles, thus highlighting a linear relationship between CETN2 expression and AD progression. CETN2-positive astrocytes were dispersed in the entorhinal cortex with a clustered pattern and colocalized with reactive glia markers STAT3, NFATc3, and YKL-40, indicating a human-specific role in AD-induced astrogliosis. Collectively, our data provide the first evidence that CETN2 is part of the astrocytic calcium toolkit undergoing rearrangements in AD and adds CETN2 to the list of proteins that could play a role in disease evolution.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2158-2177"},"PeriodicalIF":5.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cover Image, Volume 72, Issue 10 封面图片,第 72 卷第 10 期
IF 5.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-14 DOI: 10.1002/glia.24411
Martha M. Rangel-Sosa, Fanny Mann, Sophie Chauvet

Cover Illustration: 3D remodeling of reprogrammed non-myelinated Schwann cells and their associated sympathetic axons in metaplastic pancreatic lesions compared to adjacent tissue. 3D visualization of a cleared pancreatic section from a mouse with chronic pancreatitis. The transparent purple volume encompassed a metaplastic lesion with increased density of Schwann cells (in red) and sympathetic axons (in green), while the blue volume represents adjacent tissue with minimal metaplastic and neural changes. Schwann cells were labeled with anti-GFRA3, sympathetic axons with anti-TH and metaplastic cells with anti-CK19, in cyan. (See Chauvet, S., et al, https://doi.org/10.1002/glia.24586)

封面插图:与邻近组织相比,变性胰腺病变中重新编程的非髓鞘化许旺细胞及其相关交感神经轴突的三维重塑。慢性胰腺炎小鼠胰腺切片的三维可视化。透明的紫色区域包括变性病灶,其中许旺细胞(红色)和交感神经轴突(绿色)密度增加,而蓝色区域代表变性和神经变化最小的邻近组织。用抗-GFRA3标记许旺细胞,用抗-TH标记交感神经轴突,用抗-CK19标记变性细胞(青色)。(见 Chauvet, S. 等人,https://doi.org/10.1002/glia.24586)
{"title":"Cover Image, Volume 72, Issue 10","authors":"Martha M. Rangel-Sosa,&nbsp;Fanny Mann,&nbsp;Sophie Chauvet","doi":"10.1002/glia.24411","DOIUrl":"https://doi.org/10.1002/glia.24411","url":null,"abstract":"<p>Cover Illustration: 3D remodeling of reprogrammed non-myelinated Schwann cells and their associated sympathetic axons in metaplastic pancreatic lesions compared to adjacent tissue. 3D visualization of a cleared pancreatic section from a mouse with chronic pancreatitis. The transparent purple volume encompassed a metaplastic lesion with increased density of Schwann cells (in red) and sympathetic axons (in green), while the blue volume represents adjacent tissue with minimal metaplastic and neural changes. Schwann cells were labeled with anti-GFRA3, sympathetic axons with anti-TH and metaplastic cells with anti-CK19, in cyan. (See Chauvet, S., et al, https://doi.org/10.1002/glia.24586)\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 10","pages":"C1"},"PeriodicalIF":5.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Glia
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1