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https://www.readbyqxmd.com/read/28642575/reactive-astrocytes-function-as-phagocytes-after-brain-ischemia-via-abca1-mediated-pathway
#1
Yosuke M Morizawa, Yuri Hirayama, Noubuhiko Ohno, Shinsuke Shibata, Eiji Shigetomi, Yang Sui, Junichi Nabekura, Koichi Sato, Fumikazu Okajima, Hirohide Takebayashi, Hideyuki Okano, Schuichi Koizumi
Astrocytes become reactive following various brain insults; however, the functions of reactive astrocytes are poorly understood. Here, we show that reactive astrocytes function as phagocytes after transient ischemic injury and appear in a limited spatiotemporal pattern. Following transient brain ischemia, phagocytic astrocytes are observed within the ischemic penumbra region during the later stage of ischemia. However, phagocytic microglia are mainly observed within the ischemic core region during the earlier stage of ischemia...
June 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28642362/regulation-of-rhoa-by-stat3-coordinates-glial-scar-formation
#2
Francois Renault-Mihara, Masahiko Mukaino, Munehisa Shinozaki, Hiromi Kumamaru, Satoshi Kawase, Matthieu Baudoux, Toshiki Ishibashi, Soya Kawabata, Yuichiro Nishiyama, Keiko Sugai, Kaori Yasutake, Seiji Okada, Masaya Nakamura, Hideyuki Okano
Understanding how the transcription factor signal transducer and activator of transcription-3 (STAT3) controls glial scar formation may have important clinical implications. We show that astrocytic STAT3 is associated with greater amounts of secreted MMP2, a crucial protease in scar formation. Moreover, we report that STAT3 inhibits the small GTPase RhoA and thereby controls actomyosin tonus, adhesion turnover, and migration of reactive astrocytes, as well as corralling of leukocytes in vitro. The inhibition of RhoA by STAT3 involves ezrin, the phosphorylation of which is reduced in STAT3-CKO astrocytes...
June 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28641533/role-and-therapeutic-potential-of-astrocytes-in-amyotrophic-lateral-sclerosis
#3
Mariana Pehar, Benjamin A Harlan, Kelby M Killoy, Marcelo R Vargas
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. The molecular mechanism underlying the progressive degeneration of motor neuron remains uncertain but involves a non-cell autonomous process. In acute injury or degenerative diseases astrocytes adopt a reactive phenotype known as astrogliosis. Astrogliosis is a complex remodeling of astrocyte biology and most likely represents a continuum of potential phenotypes that affect neuronal function and survival in an injury-specific manner...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28637240/tfeb-activation-restores-migration-ability-to-tsc1-deficient-adult-neural-stem-progenitor-cells
#4
Alessandro Magini, Alice Polchi, Danila Di Meo, Giuseppina Mariucci, Krizia Sagini, Federico De Marco, Tommaso Cassano, Stefano Giovagnoli, Diego Dolcetta, Carla Emiliani
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). mTOR inhibitors are now considered the treatment of choice for TSC disease. A major pathological feature of TSC is the development of subependymal giant cell astrocytomas (SEGAs) in the brain. Nowadays, it is thought that SEGAs could be a consequence of aberrant aggregation and migration of neural stem/progenitor cells (NSPCs)...
June 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28636962/reactive-astrocytes-production-function-and-therapeutic-potential
#5
REVIEW
Shane A Liddelow, Ben A Barres
Astrocytes constitute approximately 30% of the cells in the mammalian central nervous system (CNS). They are integral to brain and spinal-cord physiology and perform many functions important for normal neuronal development, synapse formation, and proper propagation of action potentials. We still know very little, however, about how these functions change in response to immune attack, chronic neurodegenerative disease, or acute trauma. In this review, we summarize recent studies that demonstrate that different initiating CNS injuries can elicit at least two types of "reactive" astrocytes with strikingly different properties, one type being helpful and the other harmful...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636132/trpc1-and-trpc3-dependent-ca-2-signaling-in-mouse-cortical-astrocytes-affects-injury-evoked-astrogliosis-in-vivo
#6
Thabet Belkacemi, Alexander Niermann, Laura Hofmann, Ulrich Wissenbach, Lutz Birnbaumer, Petra Leidinger, Christina Backes, Eckart Meese, Andreas Keller, Xianshu Bai, Anja Scheller, Frank Kirchhoff, Stephan E Philipp, Petra Weissgerber, Veit Flockerzi, Andreas Beck
Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca(2+) . Transient receptor potential canonical (TRPC) channels may contribute to Ca(2+) influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells...
June 21, 2017: Glia
https://www.readbyqxmd.com/read/28631360/reduced-cell-attachment-to-poly-2-hydroxyethyl-methacrylate-coated-ventricular-catheters-in-vitro
#7
Brian W Hanak, Chia-Yun Hsieh, William Donaldson, Samuel R Browd, Kenneth K S Lau, William Shain
The majority of patients with hydrocephalus are dependent on ventriculoperitoneal shunts for diversion of excess cerebrospinal fluid. Unfortunately, these shunts are failure-prone and over half of all life-threatening pediatric failures are caused by obstruction of the ventricular catheter by the brain's resident immune cells, reactive microglia and astrocytes. Poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels are widely used for biomedical implants. The extreme hydrophilicity of PHEMA confers resistance to protein fouling, making it a strong candidate coating for ventricular catheters...
June 20, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28628111/interaction-of-reactive-astrocytes-with-type-i-collagen-induces-astrocytic-scar-formation-through-the-integrin-n-cadherin-pathway-after-spinal-cord-injury
#8
Masamitsu Hara, Kazu Kobayakawa, Yasuyuki Ohkawa, Hiromi Kumamaru, Kazuya Yokota, Takeyuki Saito, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada
Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28627367/nrf2-pathway-activation-upon-rotenone-treatment-in-human-ipsc-derived-neural-stem-cells-undergoing-differentiation-towards-neurons-and-astrocytes
#9
Francesca Pistollato, David Canovas-Jorda, Dimitra Zagoura, Anna Bal-Price
Activation of Nrf2/ARE signaling pathway occurs ubiquitously in most cell types upon induction of oxidative stress. Rotenone, an inhibitor of mitochondrial complex I, can be used to trigger oxidative stress, stimulate the activation of Nrf2 pathway in neuronal and astrocytic cells and assess neurotoxicity. We have previously demonstrated that an acute treatment with rotenone can induce Nrf2 activation, which leads to astrocyte activation and dopaminergic (DA) neuronal cell death in a mixed neuronal/astrocytic cell model derived from human induced pluripotent stem cells (hiPSCs)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28624504/proinsulin-protects-against-age-related-cognitive-loss-through-anti-inflammatory-convergent-pathways
#10
Rubén Corpas, Alberto M Hernández-Pinto, David Porquet, Catalina Hernández-Sánchez, Fatima Bosch, Arantxa Ortega-Aznar, Francesc Comellas, Enrique J de la Rosa, Coral Sanfeliu
Brain inflammaging is increasingly considered as contributing to age-related cognitive loss and neurodegeneration. Despite intensive research in multiple models, no clinically effective pharmacological treatment has been found yet. Here, in the mouse model of brain senescence SAMP8, we tested the effects of proinsulin, a promising neuroprotective agent that was previously proven to be effective in mouse models of retinal neurodegeneration. Proinsulin is the precursor of the hormone insulin but also upholds developmental physiological effects, particularly as a survival factor for neural cells...
June 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28624361/low-intensity-rtms-has-sex-dependent-effects-on-the-local-response-of-glia-following-a-penetrating-cortical-stab-injury
#11
Darren Clarke, Marissa A Penrose, Alan R Harvey, Jennifer Rodger, Kristyn A Bates
Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma...
June 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28621735/anti-inflammatory-and-anti-oxidant-potential-of-the-root-extract-and-constituents-of-doronicum-austriacum
#12
Stefania Marzocco, Simona Adesso, Mostafa Alilou, Hermann Stuppner, Stefan Schwaiger
Doronicum austriacum Jacq., Asteraceae, is a plant which is used in traditional alpine medicine. Historical sources describe the medical use of the root, but up until now only a few studies evaluated its pharmacological properties. The evaluation of the dichloromethane extract, and its major compounds for their anti-inflammatory and anti-oxidant potential was performed in macrophages J774A.1 and C6 astrocytes. Nitric oxide (NO) and reactive oxygen species (ROS) release, as well as nitrotyrosine formation, were evaluated...
June 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28620279/interleukin-6-deficiency-attenuates-retinal-ganglion-cell-axonopathy-and-glaucoma-related-vision-loss
#13
Franklin D Echevarria, Cathryn R Formichella, Rebecca M Sappington
The pleotropic cytokine interleukin-6 (IL-6) is implicated in retinal ganglion cell (RGC) survival and degeneration, including that associated with glaucoma. IL-6 protects RGCs from pressure-induced apoptosis in vitro. However, it is unknown how IL-6 impacts glaucomatous degeneration in vivo. To study how IL-6 influences glaucomatous RGC axonopathy, accompanying glial reactivity, and resultant deficits in visual function, we performed neural tracing, histological, and neurobehavioral assessments in wildtype (B6;129SF2/J; WT) and IL-6 knock-out mice (B6;129S2-IL6(t)(m1kopf)/J; IL-6-/-) after 8 weeks of unilateral or bilateral microbead-induced glaucoma (microbead occlusion model)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28617444/heme-oxygenase-1-derived-carbon-monoxide-suppresses-a%C3%AE-1-42-toxicity-in-astrocytes
#14
Nishani T Hettiarachchi, John P Boyle, Mark L Dallas, Moza M Al-Owais, Jason L Scragg, Chris Peers
Neurodegeneration in Alzheimer's disease (AD) is extensively studied, and the involvement of astrocytes and other cell types in this process has been described. However, the responses of astrocytes themselves to amyloid β peptides ((Aβ; the widely accepted major toxic factor in AD) is less well understood. Here, we show that Aβ(1-42) is toxic to primary cultures of astrocytes. Toxicity does not involve disruption of astrocyte Ca(2+) homeostasis, but instead occurs via formation of the toxic reactive species, peroxynitrite...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28612258/downregulated-glia-interplay-and-increased-mirna-155-as-promising-markers-to-track-als-at-an%C3%A2-early-stage
#15
Carolina Cunha, Catarina Santos, Cátia Gomes, Adelaide Fernandes, Alexandra Marçal Correia, Ana Maria Sebastião, Ana Rita Vaz, Dora Brites
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence of specific targets and biomarkers compromise the development of new therapeutic strategies and of innovative tools to stratify patients and assess their responses to treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions in the spinal cord of SOD1 (G93A) mice, at presymptomatic and symptomatic stages to identify stage-specific biomarkers and potential targets. Results showed that in the presymptomatic stage, there are alterations in both astrocytes and microglia, which comprise decreased expression of GFAP and S100B and upregulation of GLT-1, as well as reduced expression of CD11b, M2-phenotype markers, and a set of inflammatory mediators...
June 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28607171/astrocyte-transforming-growth-factor-beta-1-protects-synapses-against-a%C3%AE-oligomers-in-alzheimer-s-disease-model
#16
Luan Pereira Diniz, Vanessa Tortelli, Isadora Matias, Juliana Morgado, Ana Paula Bérgamo Araujo, Helen M Melo, Gisele S Seixas da Silva, Soniza V Alves-Leon, Jorge M de Souza, Sergio T Ferreira, Fernanda G De Felice, Flávia Carvalho Alcantara Gomes
Alzheimer's disease (AD) is characterized by progressive cognitive decline, increasingly attributed to neuronal dysfunction induced by amyloid-β oligomers (AβOs). Although the impact of AβOs on neurons has been extensively studied, only recently have the possible effects of AβOs on astrocytes begun to be investigated. Given the key roles of astrocytes in synapse formation, plasticity and function, we sought to investigate the impact of AβOs on astrocytes, and to determine if this impact is related to the deleterious actions of AβOs on synapses...
June 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28598994/asarone-from-acori-tatarinowii-rhizome-prevents-oxidative-stress-induced-cell-injury-in-cultured-astrocytes-a-signaling-triggered-by-akt-activation
#17
Kelly Y C Lam, Ping Yao, Huaiyou Wang, Ran Duan, Tina T X Dong, Karl W K Tsim
Acori Tatarinowii Rhizome (ATR; the dried rhizome of Acori tatarinowii Schott) is a well-known herb being used for mental disorder in China and Asia. Volatile oil is considered as the active ingredient of ATR, and asarones account for more than 90% of total volatile oil. Here, the protective effects of ATR oil and asarones, both α-asarone and β-asarone, were probed in cultured rat astrocytes. The cyto-protective effect of ATR oil and asarones against tBHP-induced astrocyte injury was revealed, and additionally ATR oil and asarones reduced the tBHP-induced intracellular reactive oxygen species (ROS) accumulation...
2017: PloS One
https://www.readbyqxmd.com/read/28598192/evaluation-of-a-human-neural-stem-cell-culture-method-for-prediction-of-the-neurotoxicity-of-anti-epileptics
#18
Abdal-Jabbar Al-Rubai, Peter Wigmore, Margaret K Pratten
Human neural stem cells have been proposed as an in vitro model to predict neurotoxicity. In this study, the potential of in vitro cultures of human-derived neurospheres to predict the effects of various anti-epileptic drugs (sodium valproate, phenytoin, carbamazepine and phenobarbitone) was evaluated. In general, these drugs had no significant effects on cell viability, total cellular protein, and neuronal process length at low doses, but at high doses these parameters were reduced significantly. Therapeutic doses of sodium valproate and phenytoin had a clear effect on neurosphere size and cell migration, with a significant reduction in both parameters when compared with the control group...
May 2017: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/28597918/inflammation-in-the-developing-rat-modulates-astroglial-reactivity-to-seizures-in-the-mature-brain
#19
Zuzanna Setkowicz, Emilia Kosonowska, Krzysztof Janeczko
Astrocytes participate in neuronal development and excitability, and produce factors enhancing or suppressing inflammatory processes occurring due to neurodegenerative diseases, such as epilepsy. Seizures, in turn, trigger the release of inflammatory mediators, causing structural and functional changes in the brain. Therefore, it appears reasonable to determine whether generalized inflammation at developmental periods can affect astrocyte reactivity to epileptic seizures occurring in the adult brain. Lipopolysaccharide (LPS) was injected in 6- or 30-day-old rats (P6 or P30, respectively)...
June 9, 2017: Journal of Anatomy
https://www.readbyqxmd.com/read/28597061/progressive-accumulation-of-autofluorescent-granules-in-macrophages-in-rat-striatum-after-systemic-3-nitropropionic-acid-a-correlative-light-and-electron-microscopic-study
#20
Tae-Ryong Riew, Hong Lim Kim, Jeong-Heon Choi, Xuyan Jin, Yoo-Jin Shin, Mun-Yong Lee
A variety of tissue biomolecules and intracellular structures are known to be autofluorescent. However, autofluorescent signals in brain tissues often confound analysis of the fluorescent markers used for immunohistochemistry. While investigating tissue and cellular pathologies induced by 3-nitropropionic acid, a mitochondrial toxin selective for striatal neurons, we encountered many autofluorescent signals confined to the lesion core. These structures were excited by blue (wavelength = 488 nm) and yellow-orange (555 nm), but not by red (639 nm) or violet (405 nm) lasers, indicating that this autofluorescence overlaps with the emission spectra of commonly used fluorophores...
June 9, 2017: Histochemistry and Cell Biology
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