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Unique Astrocyte Cytoskeletal and Nuclear Morphology in a Three-Dimensional Tissue-Engineered Rostral Migratory Stream. 三维组织工程吻侧迁移流中独特的星形胶质细胞骨架和核形态。
Pub Date : 2022-03-01 DOI: 10.3390/neuroglia3010003
Erin M Purvis, John C O'Donnell, D Kacy Cullen

Neural precursor cells (NPCs) are generated in the subventricular zone (SVZ) and travel through the rostral migratory stream (RMS) to replace olfactory bulb interneurons in the brains of most adult mammals. Following brain injury, SVZ-derived NPCs can divert from the RMS and migrate toward injured brain regions but arrive in numbers too low to promote functional recovery without experimental intervention. Our lab has biofabricated a "living scaffold" that replicates the structural and functional features of the endogenous RMS. This tissue-engineered rostral migratory stream (TE-RMS) is a new regenerative medicine strategy designed to facilitate stable and sustained NPC delivery into neuron-deficient brain regions following brain injury or neurodegenerative disease and an in vitro tool to investigate the mechanisms of neuronal migration and cell-cell communication. We have previously shown that the TE-RMS replicates the basic structure and protein expression of the endogenous RMS and can direct immature neuronal migration in vitro and in vivo. Here, we further describe profound morphological changes that occur following precise physical manipulation and subsequent self-assembly of astrocytes into the TE-RMS, including significant cytoskeletal rearrangement and nuclear elongation. The unique cytoskeletal and nuclear architecture of TE-RMS astrocytes mimics astrocytes in the endogenous rat RMS. Advanced imaging techniques reveal the unique morphology of TE-RMS cells that has yet to be described of astrocytes in vitro. The TE-RMS offers a novel platform to elucidate astrocyte cytoskeletal and nuclear dynamics and their relationship to cell behavior and function.

在大多数成年哺乳动物的大脑中,神经前体细胞(Neural precursor cells, npc)产生于脑室下区(SVZ),并通过吻侧迁移流(rostral migratory stream, RMS)取代嗅球中间神经元。脑损伤后,svz衍生的npc可以从RMS转移到受伤的脑区域,但数量过少,如果没有实验干预,无法促进功能恢复。我们的实验室已经生物制造了一个“活支架”,它复制了内源性RMS的结构和功能特征。这种组织工程吻侧迁移流(TE-RMS)是一种新的再生医学策略,旨在促进在脑损伤或神经退行性疾病后稳定和持续地将鼻咽癌输送到神经元缺陷的脑区域,也是研究神经元迁移和细胞间通讯机制的体外工具。我们之前已经证明TE-RMS复制了内源性RMS的基本结构和蛋白质表达,并可以在体外和体内指导未成熟神经元的迁移。在这里,我们进一步描述了在精确的物理操作和随后星形胶质细胞自组装到TE-RMS后发生的深刻形态学变化,包括显著的细胞骨架重排和核伸长。TE-RMS星形胶质细胞独特的细胞骨架和核结构模仿内源性大鼠RMS中的星形胶质细胞。先进的成像技术揭示了TE-RMS细胞的独特形态,但尚未在体外描述星形胶质细胞。TE-RMS为阐明星形胶质细胞骨架和核动力学及其与细胞行为和功能的关系提供了一个新的平台。
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引用次数: 0
Glia Excitation in the CNS Modulates Intact Behaviors and Sensory-CNS-Motor Circuitry 中枢神经系统中的神经胶质兴奋调节完整的行为和感觉-中枢-运动回路
Pub Date : 2022-02-28 DOI: 10.3390/neuroglia3010002
Shelby McCubbin, D. Harrison, R. Cooper
Glial cells play a role in many important processes, though the mechanisms through which they affect neighboring cells are not fully known. Insights may be gained by selectively activating glial cell populations in intact organisms utilizing the activatable channel proteins channel rhodopsin (ChR2XXL) and TRPA1. Here, the impacts of the glial-specific expression of these channels were examined in both larval and adult Drosophila. The Glia > ChR2XXL adults and larvae became immobile when exposed to blue light and TRPA1-expressed Drosophila upon heat exposure. The chloride pump expression in glia > eNpHR animals showed no observable differences in adults or larvae. In the in situ neural circuit activity of larvae in the Glia > ChR2XXL, the evoked activity first became more intense with concurrent light exposure, and then the activity was silenced and slowly picked back up after light was turned off. This decrease in motor nerve activity was also noted in the intact behaviors for Glia > ChR2XXL and Glia > TRPA1 larvae. As a proof of concept, this study demonstrated that activation of the glia can produce excessive neural activity and it appears with increased excitation of the glia and depressed motor neuron activity.
神经胶质细胞在许多重要的过程中发挥作用,尽管它们影响邻近细胞的机制尚不完全清楚。利用可激活的通道蛋白通道视紫红质(ChR2XXL)和TRPA1选择性激活完整生物体中的胶质细胞群,可能会获得新的见解。在这里,这些通道的神经胶质特异性表达的影响被检查在幼虫和成年果蝇。在蓝光照射下,胶质细胞> ChR2XXL成虫和幼虫变得不动,而trpa1表达的果蝇在热照射下变得不动。胶质> eNpHR动物中氯离子泵的表达在成虫和幼虫中无明显差异。在Glia > ChR2XXL幼虫的原位神经回路活动中,在同时光照下,激活活动首先变得更加强烈,然后在光照关闭后,激活活动沉默并缓慢回升。在Glia > ChR2XXL和Glia > TRPA1幼虫的完整行为中也发现了运动神经活动的减少。作为概念证明,本研究表明,神经胶质细胞的激活可以产生过度的神经活动,并表现为神经胶质细胞兴奋增加和运动神经元活动抑制。
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引用次数: 0
Transplantation of Olfactory Ensheathing Cells: Properties and Therapeutic Effects after Transplantation into the Lesioned Nervous System 嗅鞘细胞移植:神经系统损伤后的特性和治疗效果
Pub Date : 2022-01-28 DOI: 10.3390/neuroglia3010001
Q. Delarue, N. Guérout
The primary olfactory system (POS) is in permanent renewal, especially the primary olfactory neurons (PON) are renewed with a turnover of around four weeks, even in adulthood. The re-growth of these axons is helped by a specific population of glial cells: the olfactory ensheathing cells (OECs). In the POS, OECs constitute an “open-channel” in which the axons of PON cause regrowth from peripheral nervous system (PNS) to central nervous system (CNS). The remarkable role played by OECs into the POS has led scientists to investigate their properties and potential beneficial effects after transplantation in different lesion models of the CNS and PNS. In this review, we will resume and discuss more than thirty years of research regarding OEC studies. Indeed, after discussing the embryonic origins of OECs, we will describe the in vitro and in vivo properties exert at physiological state by these cells. Thereafter, we will present and talk over the effects of the transplantation of OECs after spinal cord injury, peripheral injury and other CNS injury models such as demyelinating diseases or traumatic brain injury. Finally, the mechanisms exerted by OECs in these different CNS and PNS lesion paradigms will be stated and we will conclude by presenting the innovations and future directions which can be considered to improve OECs properties and allow us to envisage their use in the near future in clinical applications.
初级嗅觉系统(POS)处于永久更新中,特别是初级嗅觉神经元(PON)的更新周期约为四周,即使在成年期也是如此。这些轴突的再生是由一种特殊的神经胶质细胞群帮助的:嗅鞘细胞(OECs)。在POS中,oec构成了一个“开放通道”,在这个通道中,PON的轴突使外周神经系统(PNS)向中枢神经系统(CNS)再生。oec在POS中所起的显著作用促使科学家们研究了它们在不同中枢神经系统和PNS病变模型中移植后的特性和潜在的有益作用。在这篇综述中,我们将回顾和讨论三十多年来关于OEC研究的研究。事实上,在讨论了oec的胚胎起源之后,我们将描述这些细胞在生理状态下发挥的体外和体内特性。随后,我们将介绍和讨论oec移植在脊髓损伤、外周损伤以及脱髓鞘疾病或创伤性脑损伤等其他CNS损伤模型后的作用。最后,我们将阐述oec在这些不同的CNS和PNS病变范例中的作用机制,并提出可以考虑改善oec性能的创新和未来方向,并让我们设想它们在不久的将来在临床应用中的应用。
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引用次数: 2
Neuroprotective and Anti-Microglial Activation Effects of Tocotrienols in Brains of Lipopolysaccharide-Induced Inflammatory Model Mice Tocotrienols对脂多糖诱导的炎症模型小鼠大脑的神经保护和抗小胶质细胞活化作用
Pub Date : 2021-12-16 DOI: 10.3390/neuroglia2010009
S. Okuyama, M. Matsuda, Yuna Okusako, Sanae Miyauchi, Toshiki Omasa, Akiho Ozawa, M. Abe, T. Yaeno, T. Araki, A. Sawamoto, M. Nakajima, Y. Furukawa
Inflammation is the cause and/or result of many diseases in peripheral tissues and the central nervous system. Recent findings suggested that inflammation in peripheral tissue induces an inflammatory response in the brain that activates glial cells, which, in turn, induce neuronal cell dysfunction. Therefore, anti-inflammatory compounds are important for the suppression of chronic inflammation and prevention of disease. The present study revealed microglial activation in the hippocampus of the brain two days after the peripheral administration of lipopolysaccharide (LPS). Furthermore, the expression of the synaptic vesicle membrane protein, synaptophysin, in the CA3 stratum lucidum of the hippocampus was down-regulated 7 days after the LPS injection. The administration of tocotrienols, a type of vitamin E, significantly attenuated these changes in the hippocampus. Collectively, the present results demonstrated the spread of peripheral inflammatory responses to the brain, in which glial activation and neuronal dysfunction were induced, while tocotrienols exerted anti-inflammatory effects and protected neurons from damage.
炎症是外周组织和中枢神经系统许多疾病的起因和/或结果。最近的研究结果表明,外周组织的炎症会在大脑中引起炎症反应,从而激活神经胶质细胞,进而诱导神经元细胞功能障碍。因此,抗炎化合物对抑制慢性炎症和预防疾病很重要。本研究揭示了在外周给药脂多糖(LPS)两天后,大脑海马的小胶质细胞激活。注射LPS后7 d,海马CA3透明层突触泡膜蛋白synaptophysin表达下调。生育三烯醇(一种维生素E)的服用显著减弱了海马体中的这些变化。总的来说,目前的结果表明外周炎症反应向大脑的扩散,其中神经胶质激活和神经元功能障碍被诱导,而生育三烯醇发挥抗炎作用并保护神经元免受损伤。
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引用次数: 0
Molecular and Functional Characterization of Caveolae in Mixed Cultures of Human NT-2 Neurons and Astrocytes 人NT-2神经元和星形胶质细胞混合培养小窝的分子和功能特征
Pub Date : 2021-12-08 DOI: 10.3390/neuroglia2010008
J. Sandhu, M. Ribecco‐Lutkiewicz, A. Abulrob
Caveolae are plasma membrane invaginations that are enriched in cholesterol-binding proteins called caveolins. The presence of caveolae and caveolins in mixed cultures of human neurons and glia has not been investigated. Here, we sought to determine the presence of caveolae and caveolins in human NTera-2 (NT2/D1) cells, differentiated with retinoic acid into neuron-like (NT2/N) and astrocyte-like (NT2/A) cells. We found that while caveolin-3 mRNA levels remained relatively constant, caveolin-1 and -2 levels were upregulated in NT2/A and downregulated in NT2/N. No caveolin-1 immunoreactivity was detected in NT2/N. Electron microscopy revealed numerous flask-shaped invaginations (~86–102 nm in diameter) in the plasma membrane of NT2/A and NT2/N cells, while only few were detected in NT2/D1 cells. Immunoelectron microscopy localized caveolin-1 gold particles in the flask-shaped structures on plasmalemma and cytoplasmic vesicles of NT2/A cells. Furthermore, NT2/A endocytosed Alexa 488 conjugated-cholera toxin B subunit (CTX-B) through a caveolae- and clathrin-dependent pathway, whereas NT2/N endocytosed CTX-B through a caveolae-independent pathway. We have established that while NT2/A expressed functional caveolae, the molecular identity of the plasma membrane invaginations in NT2/N is unknown. The expression of caveolin proteins was differentially regulated in these cells. Taken together, our findings support the usefulness of the human NT2 model system to study the role of caveolins in neuron–glia communication, and their involvement in brain health and disease.
小窝蛋白是质膜内陷,富含胆固醇结合蛋白,称为小窝蛋白。在人类神经元和神经胶质细胞的混合培养中,小窝和小窝蛋白的存在尚未得到研究。在这里,我们试图确定人NTera-2(NT2/D1)细胞中小窝和小窝蛋白的存在,该细胞用维甲酸分化为神经元样(NT2/N)和星形胶质细胞样(NT2/1)细胞。我们发现,虽然小窝蛋白-3 mRNA水平保持相对恒定,但小窝蛋白-1和-2水平在NT2/A中上调,在NT2/N中下调。在NT2/N中未检测到caveolin-1免疫反应性。电子显微镜显示,NT2/A和NT2/N细胞的质膜上有许多烧瓶状的凹陷(直径约86–102 nm),而在NT2/D1细胞中仅检测到少量凹陷。免疫电子显微镜将小窝蛋白-1金颗粒定位在NT2/A细胞质膜和细胞质小泡上的烧瓶状结构中。此外,NT2/A通过小窝和网格蛋白依赖性途径内吞Alexa 488偶联霍乱毒素B亚基(CTX-B),而NT2/N通过小窝非依赖性途径外吞CTX-B。我们已经证实,虽然NT2/A表达功能性小窝,但NT2/N中质膜内陷的分子身份尚不清楚。小窝蛋白的表达在这些细胞中受到不同的调节。总之,我们的发现支持了人类NT2模型系统在研究小窝蛋白在神经元-神经胶质细胞通讯中的作用及其与大脑健康和疾病的关系方面的有用性。
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引用次数: 1
The Effect of Optogenetically Activating Glia on Neuronal Function 视激活胶质细胞对神经元功能的影响
Pub Date : 2021-10-22 DOI: 10.3390/neuroglia2010007
Cecilia Pankau, Shelby McCubbin, R. Cooper
Glia, or glial cells, are considered a vital component of the nervous system, serving as an electrical insulator and a protective barrier from the interstitial (extracellular) media. Certain glial cells (i.e., astrocytes, microglia, and oligodendrocytes) within the CNS have been shown to directly affect neural functions, but these properties are challenging to study due to the difficulty involved with selectively-activating specific glia. To overcome this hurdle, we selectively expressed light-sensitive ion channels (i.e., channel rhodopsin, ChR2-XXL) in glia of larvae and adult Drosophila melanogaster. Upon activation of ChR2, both adults and larvae showed a rapid contracture of body wall muscles with the animal remaining in contracture even after the light was turned off. During ChR2-XXL activation, electrophysiological recordings of evoked excitatory junction potentials within body wall muscles of the larvae confirmed a train of motor nerve activity. Additionally, when segmental nerves were transected from the CNS and exposed to light, there were no noted differences in quantal or evoked responses. This suggests that there is not enough expression of ChR2-XXL to influence the segmental axons to detect in our paradigm. Activation of the glia within the CNS is sufficient to excite the motor neurons.
神经胶质细胞被认为是神经系统的重要组成部分,作为电绝缘体和细胞间质(细胞外)介质的保护屏障。中枢神经系统内的某些胶质细胞(即星形胶质细胞、小胶质细胞和少突胶质细胞)已被证明直接影响神经功能,但由于选择性激活特定胶质细胞的困难,这些特性的研究具有挑战性。为了克服这一障碍,我们在果蝇幼虫和成虫的神经胶质中选择性地表达了光敏离子通道(即通道视紫红质,ChR2-XXL)。ChR2激活后,成虫和幼虫均表现出体壁肌肉的快速挛缩,即使在关灯后仍保持挛缩状态。在ChR2-XXL激活期间,幼虫体壁肌肉的诱发兴奋连接电位的电生理记录证实了运动神经活动的序列。此外,当从中枢神经系统中截取节段神经并暴露在光线下时,在量子或诱发反应方面没有明显的差异。这表明在我们的范例中,没有足够的ChR2-XXL表达来影响节段性轴突。中枢神经系统内神经胶质的激活足以刺激运动神经元。
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引用次数: 1
Direct Deviations in Astrocyte Free Ca2+ Concentration Control Multiple Arteriole Tone States 星形胶质细胞游离Ca2+浓度的直接偏差控制多小动脉张力状态
Pub Date : 2021-10-14 DOI: 10.3390/neuroglia2010006
J. Haidey, G. Gordon
Astrocytes elicit bidirectional control of microvascular diameter in acutely isolated brain slices through vasoconstriction and vasodilation pathways that can be differentially recruited via the free Ca2+ concentration in endfeet and/or the metabolic status of the tissue. However, the Ca2+-level hypothesis has not been tested using direct manipulation. To overcome this, we used Ca2+-clamp whole-cell patching of peri-arteriole astrocytes to change astrocyte-free Ca2+ to different concentrations and examined the vascular response. We discovered that clamping Ca2+ at the approximate resting value (100 nM) had no impact on arteriole diameter in a pre-constricted arteriole. However, a moderate elevation to 250 nM elicited sustained vasodilation that was blocked by the COX-1 antagonist SC-560 (500 nM). The vasodilation to 250 nM Ca2+ was sensitive to the metabolic state, as it converted to vasoconstriction when oxygen tension was dramatically elevated. In normal oxygen, clamping astrocyte Ca2+ well above the resting level (750 nM) produced sustained vasoconstriction, which converted to vasodilation in the 20-HETE blocker HET0016 (1 μM). This response was fully blocked by the addition of SC-560 (500 nM), showing that 20-HETE-induced vasoconstriction dominated the dilatory action of COX-1. These data demonstrate that direct changes in astrocyte free Ca2+ can control multiple arteriole tone states through different mediators.
星形胶质细胞通过血管收缩和血管舒张途径对急性分离的脑切片中的微血管直径进行双向控制,这些途径可以通过端足中的游离Ca2+浓度和/或组织的代谢状态来不同地募集。然而,Ca2+水平假说尚未通过直接操作进行验证。为了克服这一问题,我们使用Ca2+钳全细胞修补小动脉周围星形胶质细胞,将星形胶质细胞游离Ca2+改变为不同浓度,并检测血管反应。我们发现,在预收缩的小动脉中,将Ca2+夹持在近似静止值(100nM)对小动脉直径没有影响。然而,适度升高至250nM引起持续的血管舒张,其被COX-1拮抗剂SC-560(500nM)阻断。血管舒张至250 nM Ca2+对代谢状态敏感,因为当氧张力显著升高时,它转化为血管收缩。在正常氧气中,将星形胶质细胞Ca2+钳制在远高于静息水平(750 nM)的水平会产生持续的血管收缩,在20-HETE阻断剂HET0016(1μM)中转化为血管舒张。通过添加SC-560(500nM)完全阻断了这种反应,表明20 HETE诱导的血管收缩主导了COX-1的扩张作用。这些数据表明,星形胶质细胞游离Ca2+的直接变化可以通过不同的介质控制多种小动脉张力状态。
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引用次数: 1
Neurovascular Coupling in Seizures 癫痫发作中的神经血管耦合
Pub Date : 2021-10-11 DOI: 10.3390/neuroglia2010005
G. Teskey, C. Tran
Neurovascular coupling is a key control mechanism in cerebral blood flow (CBF) regulation. Importantly, this process was demonstrated to be affected in several neurological disorders, including epilepsy. Neurovascular coupling (NVC) is the basis for functional brain imaging, such as PET, SPECT, fMRI, and fNIRS, to assess and map neuronal activity, thus understanding NVC is critical to properly interpret functional imaging signals. However, hemodynamics, as assessed by these functional imaging techniques, continue to be used as a surrogate to map seizure activity; studies of NVC and cerebral blood flow control during and following seizures are rare. Recent studies have provided conflicting results, with some studies showing focal increases in CBF at the onset of a seizure while others show decreases. In this brief review article, we provide an overview of the current knowledge state of neurovascular coupling and discuss seizure-related alterations in neurovascular coupling and CBF control.
神经血管耦合是脑血流调节的关键控制机制。重要的是,这一过程被证明在包括癫痫在内的几种神经系统疾病中受到影响。神经血管耦合(NVC)是脑功能成像(如PET、SPECT、fMRI和fNIRS)评估和绘制神经元活动的基础,因此理解NVC对于正确解释功能成像信号至关重要。然而,通过这些功能成像技术评估的血流动力学仍然被用作绘制癫痫发作活动的替代指标;在癫痫发作期间和之后对NVC和脑血流控制的研究很少。最近的研究提供了相互矛盾的结果,一些研究显示癫痫发作时CBF局灶性增加,而另一些研究显示CBF减少。在这篇简短的综述文章中,我们概述了神经血管耦合的当前知识状态,并讨论了与癫痫相关的神经血管耦合和CBF控制的改变。
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引用次数: 1
Hypothesis: Neuroglia Activation Due to Increased Peripheral and CNS Proinflammatory Cytokines/Chemokines with Neuroinflammation May Result in Long COVID 假设:神经炎症引起的外周和中枢神经系统促炎细胞因子/趋化因子增加导致神经胶质细胞活化可能导致长COVID
Pub Date : 2021-08-30 DOI: 10.3390/neuroglia2010004
M. Hayden
The COVID-19 pandemic has paralleled the great Spanish flu pandemic of 1918–1919 in the United States. Previous historical accounts have strongly suggested a post-viral syndrome and, currently, a post-COVID-19 viral syndrome is unquestionable, which shares many of the characteristics of myalgic encephalomyelitis/chronic fatigue syndrome that is present globally. The original term for this post-acute sequela of SARS-CoV-2 (PASC) was termed long haulers by those who were affected with this syndrome and it is now termed long COVID (LC) or PASC. International researchers and clinicians are desperately trying to better understand the pathobiological mechanisms possibly involved in this syndrome. This review aims to summarize many of the cumulated findings associated with LC/PASC and provides supportive and representative illustrations and transmission electron micrographic remodeling changes within brain tissues associated with a stress type of injury as occurs in the classic db/db and novel BTBR ob/ob obesity and diabetes mellitus mice models. These models are utilized to merely provide a response to metabolic stress injury wound healing mechanisms that are also present in humans. This review posits that neuroglial activation and chronic neuroinflammation may be a common denominator for the development of the complex LC/PASC syndrome following acute COVID-19 due to SARS-CoV-2.
新冠肺炎大流行与1918年至1919年在美国发生的西班牙流感大流行平行。先前的历史记录强烈暗示了病毒后综合征,目前,新冠肺炎后病毒综合征是无可争议的,它与全球存在的肌痛性脑脊髓炎/慢性疲劳综合征有许多共同特征。严重急性呼吸系统综合征冠状病毒2型(PASC)急性后遗症的最初术语被该综合征患者称为长期后遗症,现在称为长期新冠肺炎(LC)或PASC。国际研究人员和临床医生正在拼命地试图更好地了解这种综合征可能涉及的病理生物学机制。这篇综述旨在总结与LC/PASC相关的许多累积发现,并提供支持性和代表性的说明和与经典db/db和新型BTBR ob/ob肥胖和糖尿病小鼠模型中发生的应激型损伤相关的脑组织内的透射电子显微图重塑变化。这些模型仅用于提供对人类中也存在的代谢应激损伤伤口愈合机制的反应。这篇综述认为,神经胶质细胞活化和慢性神经炎症可能是SARS-CoV-2引起的急性新冠肺炎后复杂LC/PASC综合征发展的共同点。
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引用次数: 11
Effects of Chemically-Functionalized Single-Walled Carbon Nanotubes on the Morphology and Vitality of D54MG Human Glioblastoma Cells. 化学功能化单壁碳纳米管对D54MG人胶质母细胞瘤细胞形态和活力的影响
Pub Date : 2018-12-01 Epub Date: 2018-10-16 DOI: 10.3390/neuroglia1020022
Seantel Hopkins, Manoj K Gottipati, Vedrana Montana, Elena Bekyarova, Robert C Haddon, Vladimir Parpura

The unique properties of single-walled carbon nanotubes (SWCNTs) have made them interesting candidates for applications in biomedicine. There are diverse chemical groups that can be attached to SWCNTs in order for these tiny tubes to gain various functionalities, for example, water solubility. Due to the availability of these "functionalization" approaches, SWCNTs are seen as agents for a potential anti-cancer therapy. In this context, we tested different chemically-functionalized forms of SWCNTs to determine which modifications make them better combatants against glioblastoma (astrocytoma grade IV), the deadliest brain cancer. We investigated the effects that two types of water soluble SWCNTs, functionalized with polyethylene glycol (SWCNT-PEG) or tetrahydrofurfuryl-terminated polyethylene glycol (SWCNT-PEG-THFF), have on the morphology and vitality, that is, cell adhesion, proliferation and death rate, of the D54MG human glioblastoma cells in culture. We found that SWCNT-PEG-THFF solute, when added to culture media, makes D54MG cells less round (measured as a significant decrease, by ~23%, in the form factor). This morphological change was induced by the PEG-THFF functional group, but not the SWCNT backbone itself. We also found that SWCNT-PEG-THFF solute reduces the proliferation rate of D54MG cells while increasing the rate of cell death. The functional groups PEG and PEG-THFF, on the other hand, reduce the cell death rate of D54MG human glioma cells. These data indicate that the process of functionalization of SWCNTs for potential use as glioma therapeutics may affect their biological effects.

单壁碳纳米管(SWCNTs)的独特性质使其成为生物医学领域的有趣候选材料。为了使这些微小的管获得各种功能,例如水溶性,可以将不同的化学基团附着在SWCNTs上。由于这些“功能化”方法的可用性,SWCNTs被视为一种潜在的抗癌治疗药物。在这种情况下,我们测试了不同的化学功能化形式的SWCNTs,以确定哪种修饰使它们更好地对抗胶质母细胞瘤(星形细胞瘤IV级),这是最致命的脑癌。我们研究了用聚乙二醇(SWCNTs - peg)或端有四氢呋喃基的聚乙二醇(SWCNTs - peg - thff)功能化的两种水溶性SWCNTs对培养的D54MG人胶质母细胞瘤细胞的形态和活力(即细胞粘附、增殖和死亡率)的影响。我们发现,当swcnts - peg - thff溶质添加到培养基中时,使D54MG细胞变得不那么圆(在形状因子上显着减少了约23%)。这种形态变化是由PEG-THFF官能团引起的,而不是由swcnts骨架本身引起的。我们还发现swcnts - peg - thff溶质降低了D54MG细胞的增殖率,同时增加了细胞死亡率。另一方面,PEG和PEG- thff官能团降低了D54MG人胶质瘤细胞的细胞死亡率。这些数据表明,SWCNTs功能化的过程可能会影响其作为胶质瘤治疗药物的生物学效应。
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引用次数: 1
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Neuroglia (Basel, Switzerland)
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