Neuroglia (Basel, Switzerland)最新文献

Comparison of the Transduction Capacity of AAV5 and AAV PHP.eB Serotypes in Hippocampus Astroglia AAV5与aavphp转导能力的比较。海马星形胶质细胞eB血清型

Neuroglia (Basel, Switzerland)

Pub Date : 2023-11-01 DOI: 10.3390/neuroglia4040019

Anastasia Borodinova, Victor Ierusalimsky, Pavel Balaban

In the present study, we compared the astrocyte-transducing potential of the relatively novel engineered AAV PHP.eB serotype and the well-examined conventional AAV5 serotype. We generated the AAV-based genetic constructs with membrane-bound fluorescent markers under the control of the astroglial promoter GfaABC1D to target astrocytes in vivo, either via local injection into the hippocampus (AAV5, AAV PHP.eB) or via systemic injection in the retro-orbital venous sinus (AAV PHP.eB). We collected new data on the transduction properties of locally injected PHP.eB and AAV5 viruses. A morphological examination and immunostainings of mouse brain slices revealed a dose-dependent shift of cellular tropism for locally injected PHP.eB from astroglial to astroglial-neuronal as the concentration increased. When the high doses of PHP.eB viruses were administered systemically, we observed strong astrocyte transduction throughout the brain, as confirmed by the morphological examination and GFAP immunostaining. AAV5 exhibited consistent astrocytic expression in all tested concentrations. The obtained results suggest that AAV5 is more suitable for astrocyte targeting in routine stereotaxic viral injection experiments. The widely used engineered PHP.eB capsid was originally designed for the transduction of both neurons and glia. Dual cellular tropism of PHP.eB viruses, observed using different doses and different delivery protocols (local vs. systemic), suggests that the usage of AAV5 is more reliable for astrocyte labeling and that intrahippocampal injection is more suitable than systemic injection for the preferential labeling of hippocampal astroglia.

在本研究中，我们比较了相对新颖的工程化AAV PHP的星形细胞转导潜能。eB血清型和常规AAV5血清型。我们在星形胶质启动子GfaABC1D的控制下，用膜结合荧光标记生成了基于AAV的遗传构建体，通过局部注射到海马(AAV5, AAV PHP.eB)或通过全身注射到眶后静脉窦(AAV PHP.eB)，在体内靶向星形胶质细胞。我们收集了关于局部注射PHP的转导特性的新数据。eB和AAV5病毒。小鼠脑切片的形态学检查和免疫染色显示局部注射PHP的细胞趋向性发生剂量依赖性转移。随着浓度的增加，eB从星形胶质细胞向星形胶质神经元转移。当高剂量的PHP。我们通过形态学检查和GFAP免疫染色证实，系统地给药eB病毒后，我们观察到整个大脑有强烈的星形胶质细胞转导。AAV5在所有浓度下均表现出一致的星形细胞表达。结果表明，在常规立体定向病毒注射实验中，AAV5更适合用于星形胶质细胞靶向。广泛使用的工程化PHP。eB衣壳最初设计用于神经元和胶质细胞的转导。PHP的双细胞趋向性。观察不同剂量和不同递送方案(局部或全身)的eB病毒，表明AAV5用于星形胶质细胞标记更可靠，海马内注射比全身注射更适合用于海马星形胶质细胞的优先标记。

{"title":"Comparison of the Transduction Capacity of AAV5 and AAV PHP.eB Serotypes in Hippocampus Astroglia","authors":"Anastasia Borodinova, Victor Ierusalimsky, Pavel Balaban","doi":"10.3390/neuroglia4040019","DOIUrl":"https://doi.org/10.3390/neuroglia4040019","url":null,"abstract":"In the present study, we compared the astrocyte-transducing potential of the relatively novel engineered AAV PHP.eB serotype and the well-examined conventional AAV5 serotype. We generated the AAV-based genetic constructs with membrane-bound fluorescent markers under the control of the astroglial promoter GfaABC1D to target astrocytes in vivo, either via local injection into the hippocampus (AAV5, AAV PHP.eB) or via systemic injection in the retro-orbital venous sinus (AAV PHP.eB). We collected new data on the transduction properties of locally injected PHP.eB and AAV5 viruses. A morphological examination and immunostainings of mouse brain slices revealed a dose-dependent shift of cellular tropism for locally injected PHP.eB from astroglial to astroglial-neuronal as the concentration increased. When the high doses of PHP.eB viruses were administered systemically, we observed strong astrocyte transduction throughout the brain, as confirmed by the morphological examination and GFAP immunostaining. AAV5 exhibited consistent astrocytic expression in all tested concentrations. The obtained results suggest that AAV5 is more suitable for astrocyte targeting in routine stereotaxic viral injection experiments. The widely used engineered PHP.eB capsid was originally designed for the transduction of both neurons and glia. Dual cellular tropism of PHP.eB viruses, observed using different doses and different delivery protocols (local vs. systemic), suggests that the usage of AAV5 is more reliable for astrocyte labeling and that intrahippocampal injection is more suitable than systemic injection for the preferential labeling of hippocampal astroglia.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":"7 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135271639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Signaling of Neuregulin-Epidermal Growth Factor Receptors and Its Impact on the Nervous System 神经调节-表皮生长因子受体的信号传导及其对神经系统的影响

Neuroglia (Basel, Switzerland)

Pub Date : 2023-10-13 DOI: 10.3390/neuroglia4040018

Marzia Tagliaferro, Donatella Ponti

The activation of members of the Epidermal Growth Factor Receptor (EGFR) family (including ErbB) triggers pathways that have significant effects on cellular processes and have profound consequences both in physiological and pathological conditions. Within the nervous system, the neuregulin (NRG)/ErbB3 signaling plays a crucial role in promoting the formation and maturation of excitatory synapses. Noteworthy is ErbB3, which is actively involved in the process of cerebellar lamination and myelination. All members of the ErbB-family, in particular ErbB3, have been observed within the nuclei of various cell types, including both full-length receptors and alternative variants. One of these variants was detected in Schwann cells and in glioblastoma primary cells where it showed a neuregulin-dependent expression. It binds to promoters’ chromatin associated with genes, like ezrin, involved in the formation of Ranvier’s node. Its nucleolar localization suggests that it may play a role in ribosome biogenesis and in cell proliferation. The regulation of ErbB3 expression is a complex and dynamic process that can be influenced by different factors, including miRNAs. This mechanism appears to play a significant role in glioblastoma and is often associated with a poor prognosis. Altogether, the targeting of ErbB3 has emerged as an active area of research in glioblastoma treatment. These findings highlight the underappreciated role of ErbB3 as a significant receptor that can potentially play a pivotal role in diverse pathologies, implying the existence of a shared and intricate mechanism that warrants further investigation.

表皮生长因子受体(EGFR)家族成员(包括ErbB)的激活触发通路，对细胞过程产生重大影响，并在生理和病理条件下产生深远的影响。在神经系统中，神经调节蛋白(NRG)/ErbB3信号在促进兴奋性突触的形成和成熟中起着至关重要的作用。值得注意的是ErbB3，它积极参与小脑层压和髓鞘形成的过程。erbb家族的所有成员，特别是ErbB3，已经在各种细胞类型的细胞核中被观察到，包括全长受体和替代变体。其中一种变异在雪旺细胞和胶质母细胞瘤原代细胞中被检测到，在那里它表现出神经调节蛋白依赖的表达。它与启动子的染色质结合，这些染色质与基因相关，如ezrin，参与了兰维耶结的形成。它的核仁定位表明它可能在核糖体生物发生和细胞增殖中起作用。ErbB3的表达调控是一个复杂的动态过程，可以受到包括mirna在内的多种因素的影响。这种机制似乎在胶质母细胞瘤中起着重要作用，并且通常与预后不良有关。总之，靶向ErbB3已成为胶质母细胞瘤治疗研究的一个活跃领域。这些发现强调了ErbB3作为一种重要受体的作用，它可能在多种病理中发挥关键作用，这意味着存在一种值得进一步研究的共享和复杂的机制。

{"title":"The Signaling of Neuregulin-Epidermal Growth Factor Receptors and Its Impact on the Nervous System","authors":"Marzia Tagliaferro, Donatella Ponti","doi":"10.3390/neuroglia4040018","DOIUrl":"https://doi.org/10.3390/neuroglia4040018","url":null,"abstract":"The activation of members of the Epidermal Growth Factor Receptor (EGFR) family (including ErbB) triggers pathways that have significant effects on cellular processes and have profound consequences both in physiological and pathological conditions. Within the nervous system, the neuregulin (NRG)/ErbB3 signaling plays a crucial role in promoting the formation and maturation of excitatory synapses. Noteworthy is ErbB3, which is actively involved in the process of cerebellar lamination and myelination. All members of the ErbB-family, in particular ErbB3, have been observed within the nuclei of various cell types, including both full-length receptors and alternative variants. One of these variants was detected in Schwann cells and in glioblastoma primary cells where it showed a neuregulin-dependent expression. It binds to promoters’ chromatin associated with genes, like ezrin, involved in the formation of Ranvier’s node. Its nucleolar localization suggests that it may play a role in ribosome biogenesis and in cell proliferation. The regulation of ErbB3 expression is a complex and dynamic process that can be influenced by different factors, including miRNAs. This mechanism appears to play a significant role in glioblastoma and is often associated with a poor prognosis. Altogether, the targeting of ErbB3 has emerged as an active area of research in glioblastoma treatment. These findings highlight the underappreciated role of ErbB3 as a significant receptor that can potentially play a pivotal role in diverse pathologies, implying the existence of a shared and intricate mechanism that warrants further investigation.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":"257 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135918831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GABAA-ρ Receptors in the CNS: Their Functional, Pharmacological, and Structural Properties in Neurons and Astroglia 中枢神经系统中的GABAA-ρ受体:它们在神经元和星形胶质细胞中的功能、药理和结构特性

Neuroglia (Basel, Switzerland)

Pub Date : 2023-10-08 DOI: 10.3390/neuroglia4040017

Abraham Rosas-Arellano, Argel Estrada-Mondragón, Ataúlfo Martínez-Torres, Daniel Reyes-Haro

Gamma-aminobutyric acid (GABA) is known as the main inhibitory transmitter in the central nervous system (CNS), where it hyperpolarizes mature neurons through activation of GABAA receptors, pentameric complexes assembled by combination of subunits (α1–6, β1–3, γ1–3, δ, ε, θ, π and ρ1–3). GABAA-ρ subunits were originally described in the retina where they generate non-desensitizing Cl- currents that are insensitive to bicuculline and baclofen. However, now is known that they are widely expressed throughout the brain including glial cells. For example, whole-cell patch-clamp recordings demonstrated the functional expression of GABAA-ρ receptors in primary cultures of cerebellar astrocytes, as well as in cerebellar ependymal cells and striatal astrocytes. In these cells GABA-currents were partially blocked by TPMPA and insensitive to barbiturates. These receptors are proposed to be involved in extrasynaptic communication and dysfunction of the signaling is accompanied by reduced expression of GABAA-ρ receptors in Huntington’s disease and autism spectrum disorders (ASD). Thus, the aim of this review is to present an overview about GABAA-ρ receptors including their structure and function, as well as their importance in the excitatory/inhibitory (E/I) balance in neurodevelopment and in disease.

γ -氨基丁酸(GABA)是中枢神经系统(CNS)中主要的抑制性递质，它通过激活GABAA受体，以及由亚基(α1-6、β1-3、γ1-3、δ、ε、θ、π和ρ1-3)组合而成的五聚体复合物，使成熟神经元超极化。GABAA-ρ亚基最初在视网膜中被描述，在那里它们产生非脱敏的Cl-电流，对双库兰和巴氯芬不敏感。然而，现在已知它们在整个大脑中广泛表达，包括神经胶质细胞。例如，全细胞膜片钳记录显示，GABAA-ρ受体在小脑星形胶质细胞、小脑室管膜细胞和纹状体星形胶质细胞的原代培养中具有功能性表达。在这些细胞中，gaba电流被TPMPA部分阻断，对巴比妥酸盐不敏感。这些受体被认为参与突触外通讯，亨廷顿病和自闭症谱系障碍(ASD)的信号功能障碍伴随着GABAA-ρ受体的表达减少。因此，本文综述了GABAA-ρ受体的结构和功能，以及它们在神经发育和疾病中兴奋/抑制(E/I)平衡中的重要性。

{"title":"GABAA-ρ Receptors in the CNS: Their Functional, Pharmacological, and Structural Properties in Neurons and Astroglia","authors":"Abraham Rosas-Arellano, Argel Estrada-Mondragón, Ataúlfo Martínez-Torres, Daniel Reyes-Haro","doi":"10.3390/neuroglia4040017","DOIUrl":"https://doi.org/10.3390/neuroglia4040017","url":null,"abstract":"Gamma-aminobutyric acid (GABA) is known as the main inhibitory transmitter in the central nervous system (CNS), where it hyperpolarizes mature neurons through activation of GABAA receptors, pentameric complexes assembled by combination of subunits (α1–6, β1–3, γ1–3, δ, ε, θ, π and ρ1–3). GABAA-ρ subunits were originally described in the retina where they generate non-desensitizing Cl- currents that are insensitive to bicuculline and baclofen. However, now is known that they are widely expressed throughout the brain including glial cells. For example, whole-cell patch-clamp recordings demonstrated the functional expression of GABAA-ρ receptors in primary cultures of cerebellar astrocytes, as well as in cerebellar ependymal cells and striatal astrocytes. In these cells GABA-currents were partially blocked by TPMPA and insensitive to barbiturates. These receptors are proposed to be involved in extrasynaptic communication and dysfunction of the signaling is accompanied by reduced expression of GABAA-ρ receptors in Huntington’s disease and autism spectrum disorders (ASD). Thus, the aim of this review is to present an overview about GABAA-ρ receptors including their structure and function, as well as their importance in the excitatory/inhibitory (E/I) balance in neurodevelopment and in disease.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":"52 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135251454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combination of Engineered Expression of Polysialic Acid on Transplanted Schwann Cells and in Injured Rat Spinal Cord Promotes Significant Axonal Growth and Functional Recovery 在移植雪旺细胞和损伤大鼠脊髓中工程表达聚唾液酸可显著促进轴突生长和功能恢复

Neuroglia (Basel, Switzerland)

Pub Date : 2023-09-23 DOI: 10.3390/neuroglia4040016

Fangyou Gao, Yi Zhang, Dongsheng Wu, Juan Luo, Svetlana Gushchina, Xuenong Bo

Providing cellular support and modifying the glial scar around the lesion are two key strategies for promoting axonal regeneration after spinal cord injury. We showed previously that over-expressing polysialic acid (PSA) on Schwann cells (SCs) by lentiviral vector (LV)-mediated expression of polysialyltransferase (PST) facilitated their integration and migration in the injured spinal cord. We also showed that PSA over-expression in the injured spinal cord modified the glial scar and promoted the growth of ascending sensory axons. In this study, we combined the PST/SC transplantation with LV/PST injection in spinal cords after dorsal column transection and found the combined treatments led to faster and more profound locomotor functional recovery compared with animals receiving combined GFP/SC transplantation with LV/GFP injection. Histological examination showed significantly more injured corticospinal axons growing close to the lesion/transplant borders and into the caudal spinal cord in the PST group than in the GFP group. We also found over -expressing PSA around the lesion site did not cause allodynia and hyperalgesia in our injury model. These results demonstrate the promising therapeutic benefit of over-expressing PSA in transplanted SCs and spinal cord in promoting axonal growth and restoring motor function.

提供细胞支持和修复损伤周围的胶质瘢痕是促进脊髓损伤后轴突再生的两个关键策略。我们之前的研究表明，通过慢病毒载体(LV)介导的多唾液酸转移酶(PST)的表达，在雪旺细胞(SCs)上过表达多唾液酸(PSA)，促进了它们在受损脊髓中的整合和迁移。我们还发现，受损脊髓中PSA的过表达改变了胶质瘢痕，促进了上行感觉轴突的生长。在本研究中，我们将脊髓背柱横切后的PST/SC移植与LV/GFP注射联合治疗，发现与GFP/SC联合移植与LV/GFP注射相比，联合治疗能更快、更深入地恢复动物的运动功能。组织学检查显示，与GFP组相比，PST组损伤的皮质脊髓轴突生长在靠近病变/移植边界的地方，并进入脊髓尾端。我们还发现，在我们的损伤模型中，病变部位周围过表达的PSA不会引起异常性疼痛和痛觉过敏。这些结果表明，在移植的SCs和脊髓中过表达PSA在促进轴突生长和恢复运动功能方面具有良好的治疗效果。

{"title":"Combination of Engineered Expression of Polysialic Acid on Transplanted Schwann Cells and in Injured Rat Spinal Cord Promotes Significant Axonal Growth and Functional Recovery","authors":"Fangyou Gao, Yi Zhang, Dongsheng Wu, Juan Luo, Svetlana Gushchina, Xuenong Bo","doi":"10.3390/neuroglia4040016","DOIUrl":"https://doi.org/10.3390/neuroglia4040016","url":null,"abstract":"Providing cellular support and modifying the glial scar around the lesion are two key strategies for promoting axonal regeneration after spinal cord injury. We showed previously that over-expressing polysialic acid (PSA) on Schwann cells (SCs) by lentiviral vector (LV)-mediated expression of polysialyltransferase (PST) facilitated their integration and migration in the injured spinal cord. We also showed that PSA over-expression in the injured spinal cord modified the glial scar and promoted the growth of ascending sensory axons. In this study, we combined the PST/SC transplantation with LV/PST injection in spinal cords after dorsal column transection and found the combined treatments led to faster and more profound locomotor functional recovery compared with animals receiving combined GFP/SC transplantation with LV/GFP injection. Histological examination showed significantly more injured corticospinal axons growing close to the lesion/transplant borders and into the caudal spinal cord in the PST group than in the GFP group. We also found over -expressing PSA around the lesion site did not cause allodynia and hyperalgesia in our injury model. These results demonstrate the promising therapeutic benefit of over-expressing PSA in transplanted SCs and spinal cord in promoting axonal growth and restoring motor function.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135966928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glucose Transporter-2 Regulation of Male versus Female Hypothalamic Astrocyte MAPK Expression and Activation: Impact of Glucose. 葡萄糖转运蛋白-2对男性和女性下丘脑星形胶质细胞MAPK表达和激活的调节:葡萄糖的影响

Neuroglia (Basel, Switzerland)

Pub Date : 2023-09-01 DOI: 10.3390/neuroglia4030011

MadhuBabu Pasula, Sagor C Roy, Khaggeswar Bheemanapally, Paul W Sylvester, Karen P Briski

The plasma membrane glucose transporter (GLUT)-2 is unique among GLUT family proteins in that it also functions as a glucose sensor. GLUT2 imposes sex-dimorphic control of hypothalamic astrocyte glucose storage and catabolism by unknown mechanisms. Mitogen-activated protein kinase (MAPK) signaling cascades operate within stress-sensitive signal transduction pathways. Current research employed an established primary astrocyte culture model and gene knockdown tools to investigate whether one or more of the three primary MAP kinase families are regulated by GLUT2. GLUT2 gene knockdown caused opposing adjustments in total ERK1/2 proteins in glucose-supplied male versus female astrocytes, augmenting or reducing the mean phosphorylated/total protein ratio for 44 and 42 kDa variants in these sexes. Glucose deprivation amplified this ratio for both ERK1/2 variants, albeit by a larger magnitude in male; GLUT2 siRNA exacerbated this stimulatory response in males only. Phosphorylated/total p38 MAPK protein ratios were up-regulated by GLUT2 knockdown in male, but not female astrocytes. Glucose-deprived astrocytes exhibited no change (male) or reduction (female) in this ratio after GLUT2 gene silencing. GLUT2 siRNA increased the phosphorylated/total protein ratio for 54 and 46 kDa SAPK/JNK proteins in each sex when glucose was present. However, glucose withdrawal suppressed (male) or amplified (female) these ratios, while GLUT2 knockdown attenuated these inverse responses. Results show that GLUT2 inhibits ERK1/2, p38, and SAPK/JNK MAPK activity in male, but differentially stimulates and inhibits activity of these signaling pathways in female hypothalamic astrocytes. Glucoprivation induces divergent adjustments in astrocyte p38 MAPK and SAPK/JNK activities. The findings demonstrate a stimulatory role for GLUT2 in p38 MAPK activation in glucose-starved female astrocytes, but can act as either an inhibitor or inducer of SAPK/JNK activation in glucose-deprived male versus female glial cells, respectively.

质膜葡萄糖转运蛋白(GLUT)-2在GLUT家族蛋白中是独特的，因为它也具有葡萄糖传感器的功能。GLUT2通过未知机制对下丘脑星形胶质细胞葡萄糖储存和分解代谢施加性别二态控制。丝裂原活化蛋白激酶(MAPK)信号级联在应激敏感信号转导途径中运作。目前的研究采用建立的原代星形胶质细胞培养模型和基因敲低工具来研究三个主要MAP激酶家族中的一个或多个是否受GLUT2调控。GLUT2基因敲除导致葡萄糖供应的男性和女性星形胶质细胞中ERK1/2总蛋白的相反调节，增加或降低这些性别中44和42 kDa变异的平均磷酸化/总蛋白比率。葡萄糖剥夺放大了这两种ERK1/2变异的比例，尽管在男性中幅度更大;GLUT2 siRNA仅在雄性中加剧了这种刺激反应。GLUT2敲低可上调雄性星形胶质细胞中磷酸化/总p38 MAPK蛋白的比例，而雌性星形胶质细胞中没有。在GLUT2基因沉默后，葡萄糖剥夺的星形胶质细胞在这一比例上没有变化(雄性)或减少(雌性)。当葡萄糖存在时，GLUT2 siRNA增加了两性中54和46 kDa SAPK/JNK蛋白的磷酸化/总蛋白比率。然而，葡萄糖戒断抑制(男性)或放大(女性)这些比率，而GLUT2敲低则减弱这些反向反应。结果表明，GLUT2在雄性中抑制ERK1/2、p38和SAPK/JNK MAPK的活性，但在雌性下丘脑星形胶质细胞中刺激和抑制这些信号通路的活性存在差异。葡萄糖活化诱导星形胶质细胞p38 MAPK和SAPK/JNK活性的不同调节。研究结果表明，在葡萄糖缺乏的雌性星形胶质细胞中，GLUT2在p38 MAPK激活中具有刺激作用，但在葡萄糖缺乏的雄性和雌性胶质细胞中，GLUT2分别可以作为SAPK/JNK激活的抑制剂或诱导剂。

{"title":"Glucose Transporter-2 Regulation of Male versus Female Hypothalamic Astrocyte MAPK Expression and Activation: Impact of Glucose.","authors":"MadhuBabu Pasula, Sagor C Roy, Khaggeswar Bheemanapally, Paul W Sylvester, Karen P Briski","doi":"10.3390/neuroglia4030011","DOIUrl":"https://doi.org/10.3390/neuroglia4030011","url":null,"abstract":"<p><p>The plasma membrane glucose transporter (GLUT)-2 is unique among GLUT family proteins in that it also functions as a glucose sensor. GLUT2 imposes sex-dimorphic control of hypothalamic astrocyte glucose storage and catabolism by unknown mechanisms. Mitogen-activated protein kinase (MAPK) signaling cascades operate within stress-sensitive signal transduction pathways. Current research employed an established primary astrocyte culture model and gene knockdown tools to investigate whether one or more of the three primary MAP kinase families are regulated by GLUT2. GLUT2 gene knockdown caused opposing adjustments in total ERK1/2 proteins in glucose-supplied male versus female astrocytes, augmenting or reducing the mean phosphorylated/total protein ratio for 44 and 42 kDa variants in these sexes. Glucose deprivation amplified this ratio for both ERK1/2 variants, albeit by a larger magnitude in male; GLUT2 siRNA exacerbated this stimulatory response in males only. Phosphorylated/total p38 MAPK protein ratios were up-regulated by GLUT2 knockdown in male, but not female astrocytes. Glucose-deprived astrocytes exhibited no change (male) or reduction (female) in this ratio after GLUT2 gene silencing. GLUT2 siRNA increased the phosphorylated/total protein ratio for 54 and 46 kDa SAPK/JNK proteins in each sex when glucose was present. However, glucose withdrawal suppressed (male) or amplified (female) these ratios, while GLUT2 knockdown attenuated these inverse responses. Results show that GLUT2 inhibits ERK1/2, p38, and SAPK/JNK MAPK activity in male, but differentially stimulates and inhibits activity of these signaling pathways in female hypothalamic astrocytes. Glucoprivation induces divergent adjustments in astrocyte p38 MAPK and SAPK/JNK activities. The findings demonstrate a stimulatory role for GLUT2 in p38 MAPK activation in glucose-starved female astrocytes, but can act as either an inhibitor or inducer of SAPK/JNK activation in glucose-deprived male versus female glial cells, respectively.</p>","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":"4 3","pages":"158-171"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361449/pdf/nihms-1914681.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of Astrocytes and Blood–Brain Barrier Disruption in Alzheimer’s Disease 星形胶质细胞和血脑屏障破坏在阿尔茨海默病中的作用

Neuroglia (Basel, Switzerland)

Pub Date : 2023-08-20 DOI: 10.3390/neuroglia4030015

J. V. R. Cruz, C. Batista, L. P. Diniz, F. Mendes

The blood–brain barrier (BBB) is a highly intricate neurovascular structure that plays a crucial role in maintaining neural homeostasis by selectively allowing certain molecules to enter the central nervous system (CNS). However, in the context of Alzheimer’s Disease (AD), a progressive neurodegenerative disorder characterized by a gradual decline in cognitive function, the BBB’s functionality becomes impaired. This impairment leads to the breakdown of the barrier and disrupts its ability to regulate molecular transport effectively. Consequently, cellular infiltration into the CNS occurs, along with aberrant signaling and clearance of molecules, ultimately contributing to neurological deficits. One of the key factors implicated in the failure of amyloid-beta (Aβ) transport, a hallmark of AD, is the decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1). LRP1 plays a crucial role in facilitating the transport of Aβ across the BBB. Additionally, the increased levels of the receptor for advanced glycation end products (RAGE) further contribute to the deregulation of the BBB in AD. These molecular imbalances significantly impact Aβ clearance and contribute to the development and progression of AD. In this review, we aimed to summarize the critical aspects of Aβ transporters in the BBB that become dysfunctional during the pathogenesis of AD.

血脑屏障（BBB）是一种高度复杂的神经血管结构，通过选择性地允许某些分子进入中枢神经系统（CNS），在维持神经稳态方面发挥着至关重要的作用。然而，在阿尔茨海默病（AD）的背景下，血脑屏障的功能受损。阿尔茨海默病是一种以认知功能逐渐下降为特征的进行性神经退行性疾病。这种损伤导致屏障的破坏，并破坏其有效调节分子转运的能力。因此，细胞浸润到中枢神经系统，伴随着异常的信号传导和分子清除，最终导致神经系统缺陷。AD标志性淀粉样蛋白β（Aβ）转运失败的关键因素之一是低密度脂蛋白受体相关蛋白1（LRP1）的表达减少。LRP1在促进aβ通过血脑屏障的转运中起着至关重要的作用。此外，晚期糖基化终产物受体（RAGE）水平的升高进一步有助于AD血脑屏障的放松。这些分子失衡显著影响Aβ的清除，并有助于AD.在这篇综述中，我们旨在总结血脑屏障中Aβ转运蛋白在AD发病过程中功能失调的关键方面。

{"title":"The Role of Astrocytes and Blood–Brain Barrier Disruption in Alzheimer’s Disease","authors":"J. V. R. Cruz, C. Batista, L. P. Diniz, F. Mendes","doi":"10.3390/neuroglia4030015","DOIUrl":"https://doi.org/10.3390/neuroglia4030015","url":null,"abstract":"The blood–brain barrier (BBB) is a highly intricate neurovascular structure that plays a crucial role in maintaining neural homeostasis by selectively allowing certain molecules to enter the central nervous system (CNS). However, in the context of Alzheimer’s Disease (AD), a progressive neurodegenerative disorder characterized by a gradual decline in cognitive function, the BBB’s functionality becomes impaired. This impairment leads to the breakdown of the barrier and disrupts its ability to regulate molecular transport effectively. Consequently, cellular infiltration into the CNS occurs, along with aberrant signaling and clearance of molecules, ultimately contributing to neurological deficits. One of the key factors implicated in the failure of amyloid-beta (Aβ) transport, a hallmark of AD, is the decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1). LRP1 plays a crucial role in facilitating the transport of Aβ across the BBB. Additionally, the increased levels of the receptor for advanced glycation end products (RAGE) further contribute to the deregulation of the BBB in AD. These molecular imbalances significantly impact Aβ clearance and contribute to the development and progression of AD. In this review, we aimed to summarize the critical aspects of Aβ transporters in the BBB that become dysfunctional during the pathogenesis of AD.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49121643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overview of the Molecular Modalities and Signaling Pathways Intersecting with β-Amyloid and Tau Protein in Alzheimer’s Disease 阿尔茨海默病中β-淀粉样蛋白和Tau蛋白交叉的分子模式和信号通路综述

Neuroglia (Basel, Switzerland)

Pub Date : 2023-07-30 DOI: 10.3390/neuroglia4030014

Ahmed M. Elshazly, Melanie M. Sinanian, Diaaeldin M. Elimam, Sherin Zakaria

Alzheimer’s disease (AD) is one of the major causes of dementia and its incidence represents approximately 60–70% of all dementia cases worldwide. Many theories have been proposed to describe the pathological events in AD, including deterioration in cognitive function, accumulation of β-amyloid, and tau protein hyperphosphorylation. Infection as well as various cellular molecules, such as apolipoprotein, micro-RNA, calcium, ghrelin receptor, and probiotics, are associated with the disruption of β-amyloid and tau protein hemostasis. This review gives an overview on the integrative cellular and signaling molecules that could play a complementary role in the dysregulation of β-amyloid and tau proteins.

阿尔茨海默病(AD)是痴呆症的主要原因之一，其发病率约占全世界所有痴呆症病例的60-70%。人们提出了许多理论来描述AD的病理事件，包括认知功能的恶化、β-淀粉样蛋白的积累和tau蛋白的过度磷酸化。感染以及各种细胞分子，如载脂蛋白、微rna、钙、胃饥饿素受体和益生菌，都与β-淀粉样蛋白和tau蛋白止血的破坏有关。本文综述了在β-淀粉样蛋白和tau蛋白失调中可能发挥互补作用的整合细胞和信号分子。

引用次数: 0

Unraveling the Critical Mechanisms and Functions of Neuroglia in Spinal Cord Injuries 神经胶质细胞在脊髓损伤中的关键机制和功能

Neuroglia (Basel, Switzerland)

Pub Date : 2023-07-24 DOI: 10.3390/neuroglia4030013

Chih-Wei Zeng

In the dynamic landscape of neuroscience and regenerative medicine, the pivotal role of neuroglia, or glial cells, is increasingly being recognized [...]

在神经科学和再生医学的动态图景中，神经胶质细胞或胶质细胞的关键作用越来越被认识到[…]

引用次数: 1

A Human Microglial Cell Line Expresses γ-Aminobutyric Acid (GABA) Receptors and Responds to GABA and Muscimol by Increasing Production of IL-8 人小胶质细胞表达γ-氨基丁酸(GABA)受体，并通过增加IL-8的产生对GABA和Muscimol产生应答

Neuroglia (Basel, Switzerland)

Pub Date : 2023-06-28 DOI: 10.3390/neuroglia4030012

Ashley Wagner, Zhimin Yan, M. Kulka

Gamma-aminobutyric acid (GABA) is an essential neurotransmitter and an important regulator of neuroinflammation and disease. Microglia are important immune cells in the brain that express GABA receptors (GABAR) and respond to both GABA and GABAR agonists, yet the effect of GABA on microglial inflammatory responses is unclear. We hypothesized that GABA and GABAR agonists might modify the activation of a human microglial cell line (HMC3). We further hypothesized that Amanita muscaria extract (AME-1), which contained GABAR agonists (GABA and muscimol), would similarly stimulate HMC3. Ligand-gated GABAR (GABAAR) and G protein-coupled GABAR (GABABR) subunit expression was analyzed by qRT-PCR, metabolic activity was determined by nicotinamide adenine dinucleotide (NADH)-dependent oxidoreductase assay (XTT), reactive oxygen species (ROS) generation was analyzed by 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA), and interleukin-8 (IL-8) production was analyzed by an enzyme-linked immunosorbent assay (ELISA). HMC3 expressed several neuroreceptors such as subunits of the GABAA receptor (GABAAR). HMC3 constitutively produce IL-8 and ROS. Both muscimol and GABA stimulated HMC3 to produce more IL-8 but had no effect on constitutive ROS production. GABA and muscimol altered the morphology and Iba1 localization of HMC3. GABA, but not muscimol, increased HMC3 metabolic activity. Similarly, AME-1 induced HMC3 to produce more IL-8 but not ROS and altered cell morphology and Iba1 localization. GABA induction of IL-8 was blocked by bicuculline, an antagonist of GABAAR. AME-1-induced production of IL-8 was not blocked by bicuculline, suggesting that AME-1’s effect on HMC3 was independent of GABAAR. In conclusion, these data show that GABA and GABA agonists stimulate HMC3 to increase their production of IL-8. Mixtures that contain GABA and muscimol, such as AME-1, have similar effects on HMC3 that are independent of GABAAR.

γ -氨基丁酸(GABA)是一种必需的神经递质，是神经炎症和疾病的重要调节剂。小胶质细胞是大脑中表达GABA受体(GABAR)并对GABA和GABAR激动剂均有反应的重要免疫细胞，但GABA对小胶质细胞炎症反应的影响尚不清楚。我们假设GABA和GABAR激动剂可能会改变人小胶质细胞系(HMC3)的激活。我们进一步假设Amanita muscaria提取物(AME-1)含有GABAR激动剂(GABA和muscimol)，同样会刺激HMC3。采用qRT-PCR分析配体门控GABAR (GABAAR)和G蛋白偶联GABAR (GABABR)亚基表达，采用烟酰胺腺嘌呤二核苷酸(NADH)依赖氧化还原酶法(XTT)检测代谢活性，采用2′，7′-二氯双氢荧光素(DCFDA)检测活性氧(ROS)生成，采用酶联免疫吸附法(ELISA)检测白细胞介素-8 (IL-8)生成。HMC3表达GABAA受体亚基(GABAAR)等多种神经受体。HMC3组成性地产生IL-8和ROS。muscimol和GABA均刺激HMC3产生更多的IL-8，但对组成型ROS的产生没有影响。GABA和muscimol改变了HMC3的形态和Iba1的定位。GABA增加了HMC3的代谢活性，而muscimol没有。同样，AME-1诱导HMC3产生更多的IL-8而不是ROS，并改变细胞形态和Iba1的定位。GABA对IL-8的诱导可被GABAAR拮抗剂bicuculline阻断。双管碱未阻断AME-1诱导的IL-8的产生，提示AME-1对HMC3的作用独立于GABAAR。综上所述，这些数据表明GABA和GABA激动剂刺激HMC3增加IL-8的产生。含有GABA和muscimol的混合物，如AME-1，对独立于GABAAR的HMC3有类似的作用。

{"title":"A Human Microglial Cell Line Expresses γ-Aminobutyric Acid (GABA) Receptors and Responds to GABA and Muscimol by Increasing Production of IL-8","authors":"Ashley Wagner, Zhimin Yan, M. Kulka","doi":"10.3390/neuroglia4030012","DOIUrl":"https://doi.org/10.3390/neuroglia4030012","url":null,"abstract":"Gamma-aminobutyric acid (GABA) is an essential neurotransmitter and an important regulator of neuroinflammation and disease. Microglia are important immune cells in the brain that express GABA receptors (GABAR) and respond to both GABA and GABAR agonists, yet the effect of GABA on microglial inflammatory responses is unclear. We hypothesized that GABA and GABAR agonists might modify the activation of a human microglial cell line (HMC3). We further hypothesized that Amanita muscaria extract (AME-1), which contained GABAR agonists (GABA and muscimol), would similarly stimulate HMC3. Ligand-gated GABAR (GABAAR) and G protein-coupled GABAR (GABABR) subunit expression was analyzed by qRT-PCR, metabolic activity was determined by nicotinamide adenine dinucleotide (NADH)-dependent oxidoreductase assay (XTT), reactive oxygen species (ROS) generation was analyzed by 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA), and interleukin-8 (IL-8) production was analyzed by an enzyme-linked immunosorbent assay (ELISA). HMC3 expressed several neuroreceptors such as subunits of the GABAA receptor (GABAAR). HMC3 constitutively produce IL-8 and ROS. Both muscimol and GABA stimulated HMC3 to produce more IL-8 but had no effect on constitutive ROS production. GABA and muscimol altered the morphology and Iba1 localization of HMC3. GABA, but not muscimol, increased HMC3 metabolic activity. Similarly, AME-1 induced HMC3 to produce more IL-8 but not ROS and altered cell morphology and Iba1 localization. GABA induction of IL-8 was blocked by bicuculline, an antagonist of GABAAR. AME-1-induced production of IL-8 was not blocked by bicuculline, suggesting that AME-1’s effect on HMC3 was independent of GABAAR. In conclusion, these data show that GABA and GABA agonists stimulate HMC3 to increase their production of IL-8. Mixtures that contain GABA and muscimol, such as AME-1, have similar effects on HMC3 that are independent of GABAAR.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44279847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Focused Ultrasound-Mediated Blood–Brain Barrier Opening Best Promotes Neuroimmunomodulation through Brain Macrophage Redistribution 聚焦超声介导的血脑屏障打开通过脑巨噬细胞再分布促进神经免疫调节

Neuroglia (Basel, Switzerland)

Pub Date : 2023-05-31 DOI: 10.3390/neuroglia4020010

A. Kline-Schoder, R. Noel, H. Phatnani, V. Menon, E. Konofagou

Neuroimmunomodulation is a promising form of drug-free treatment for neurological diseases ranging from Alzheimer’s disease to depression. The evidence supporting the efficacy of focused ultrasound (FUS) neuroimmunomodulation is encouraging; however, the method has yet to be standardized, and its mechanism remains poorly understood. Methods of FUS neuroimmunomodulation can be categorized into three paradigms based on the parameters used. In the first paradigm, focused ultrasound blood–brain barrier opening (FUS-BBBO) combines FUS with microbubbles (MB) to transiently and safely induce BBB opening. In the second paradigm, focused ultrasound neuromodulation (FUS-N) harnesses the acoustic effects of FUS alone (without MB). In the third paradigm, focused ultrasound with microbubbles without BBBO (FUS + MB) combines MB with FUS below the BBBO pressure threshold—harnessing the mechanical effects of FUS without opening the barrier. Due to the recent evidence of brain macrophage modulation in response to FUS-BBBO, we provide the first direct comparison of brain macrophage modulation between all three paradigms both in the presence and absence of Alzheimer’s disease (AD) pathology. Flow cytometry and single-cell sequencing are employed to identify FUS-BBBO as the FUS paradigm, which maximizes brain macrophage modulation, including an increase in the population of neuroprotective, disease-associated microglia and direct correlation between treatment cavitation dose and brain macrophage phagocytosis. Next, we combine spatial and single-cell transcriptomics with immunohistochemical validation to provide the first characterization of brain macrophage distribution in response to FUS-BBBO. Given their relevance within neurodegeneration and perturbation response, we emphasize the analysis of three brain macrophage populations—disease- and interferon-associated microglia and central-nervous-system-associated macrophages. We find and validate the redistribution of each population with an overall trend toward increased interaction with the brain–cerebrospinal fluid barrier (BCSFB) after FUS-BBBO, an effect that is found to be more pronounced in the presence of disease pathology. This study addresses the prior lack of FUS neuroimmunomodulation paradigm optimization and mechanism characterization, identifying that FUS-BBBO best modulates brain macrophage response via complex redistribution.

神经免疫调节是一种很有前途的无药物治疗神经系统疾病的形式，从阿尔茨海默病到抑郁症。支持聚焦超声(FUS)神经免疫调节效果的证据是令人鼓舞的;然而，该方法尚未标准化，其机制仍然知之甚少。基于使用的参数，FUS神经免疫调节方法可分为三种范式。在第一种模式中，聚焦超声血脑屏障打开(FUS- bbbo)结合FUS和微泡(MB)来短暂和安全地诱导血脑屏障打开。在第二种模式中，聚焦超声神经调节(FUS- n)仅利用FUS的声学效应(不含MB)。在第三种模式中，无BBBO的微泡聚焦超声(FUS + MB)将MB与BBBO压力阈值以下的FUS结合在一起，利用FUS的机械效应而不打开屏障。由于最近有证据表明脑巨噬细胞调节对FUS-BBBO的反应，我们提供了在存在和不存在阿尔茨海默病(AD)病理的情况下，所有三种范式之间的脑巨噬细胞调节的首次直接比较。流式细胞术和单细胞测序鉴定FUS- bbbo为FUS模式，其最大限度地调节脑巨噬细胞，包括增加神经保护、疾病相关小胶质细胞的数量，以及治疗空化剂量与脑巨噬细胞吞噬的直接相关性。接下来，我们将空间和单细胞转录组学与免疫组织化学验证相结合，首次提供了FUS-BBBO对脑巨噬细胞分布的反应。鉴于它们在神经变性和扰动反应中的相关性，我们强调分析三种脑巨噬细胞群-疾病和干扰素相关的小胶质细胞和中枢神经系统相关的巨噬细胞。我们发现并验证了每个人群在FUS-BBBO后与脑-脑脊液屏障(BCSFB)相互作用增加的总体趋势，这种影响在存在疾病病理的情况下更为明显。本研究解决了先前缺乏FUS神经免疫调节模式优化和机制表征的问题，确定FUS- bbbo通过复杂的再分配来调节脑巨噬细胞反应。

{"title":"Focused Ultrasound-Mediated Blood–Brain Barrier Opening Best Promotes Neuroimmunomodulation through Brain Macrophage Redistribution","authors":"A. Kline-Schoder, R. Noel, H. Phatnani, V. Menon, E. Konofagou","doi":"10.3390/neuroglia4020010","DOIUrl":"https://doi.org/10.3390/neuroglia4020010","url":null,"abstract":"Neuroimmunomodulation is a promising form of drug-free treatment for neurological diseases ranging from Alzheimer’s disease to depression. The evidence supporting the efficacy of focused ultrasound (FUS) neuroimmunomodulation is encouraging; however, the method has yet to be standardized, and its mechanism remains poorly understood. Methods of FUS neuroimmunomodulation can be categorized into three paradigms based on the parameters used. In the first paradigm, focused ultrasound blood–brain barrier opening (FUS-BBBO) combines FUS with microbubbles (MB) to transiently and safely induce BBB opening. In the second paradigm, focused ultrasound neuromodulation (FUS-N) harnesses the acoustic effects of FUS alone (without MB). In the third paradigm, focused ultrasound with microbubbles without BBBO (FUS + MB) combines MB with FUS below the BBBO pressure threshold—harnessing the mechanical effects of FUS without opening the barrier. Due to the recent evidence of brain macrophage modulation in response to FUS-BBBO, we provide the first direct comparison of brain macrophage modulation between all three paradigms both in the presence and absence of Alzheimer’s disease (AD) pathology. Flow cytometry and single-cell sequencing are employed to identify FUS-BBBO as the FUS paradigm, which maximizes brain macrophage modulation, including an increase in the population of neuroprotective, disease-associated microglia and direct correlation between treatment cavitation dose and brain macrophage phagocytosis. Next, we combine spatial and single-cell transcriptomics with immunohistochemical validation to provide the first characterization of brain macrophage distribution in response to FUS-BBBO. Given their relevance within neurodegeneration and perturbation response, we emphasize the analysis of three brain macrophage populations—disease- and interferon-associated microglia and central-nervous-system-associated macrophages. We find and validate the redistribution of each population with an overall trend toward increased interaction with the brain–cerebrospinal fluid barrier (BCSFB) after FUS-BBBO, an effect that is found to be more pronounced in the presence of disease pathology. This study addresses the prior lack of FUS neuroimmunomodulation paradigm optimization and mechanism characterization, identifying that FUS-BBBO best modulates brain macrophage response via complex redistribution.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47562893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2