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  • Astrocyte‐T cell crosstalk regulates region‐specific neuroinflammation
    Glia (IF 5.829) Pub Date : 2020-01-21
    Jessica L. Williams; Sindhu Manivasagam; Brandon C. Smith; Julia Sim; Lauren L. Vollmer; Brian P. Daniels; John H. Russell; Robyn S. Klein
    更新日期:2020-01-22
  • Emerging technologies to study glial cells
    Glia (IF 5.829) Pub Date : 2020-01-20
    Hélène Hirbec; Nicole Déglon; Lynette C. Foo; Inbal Goshen; Jaime Grutzendler; Emilie Hangen; Tirzah Kreisel; Nathalie Linck; Julien Muffat; Sara Regio; Sybille Rion; Carole Escartin
    更新日期:2020-01-21
  • Developmental trajectory of oligodendrocyte progenitor cells in the human brain revealed by single cell RNA sequencing
    Glia (IF 5.829) Pub Date : 2020-01-20
    Kelly Perlman; Charles P. Couturier; Moein Yaqubi; Arnaud Tanti; Qiao‐Ling Cui; Florian Pernin; Jo Anne Stratton; Jiannis Ragoussis; Luke Healy; Kevin Petrecca; Roy Dudley; Myriam Srour; Jeffrey A. Hall; Timothy E. Kennedy; Naguib Mechawar; Jack P. Antel
    更新日期:2020-01-21
  • DNA methylation in Schwann cells and in oligodendrocytes
    Glia (IF 5.829) Pub Date : 2020-01-20
    Peter Arthur‐Farraj; Sarah Moyon
    更新日期:2020-01-21
  • RvE1 treatment prevents memory loss and neuroinflammation in the Ts65Dn mouse model of Down syndrome
    Glia (IF 5.829) Pub Date : 2020-01-16
    Eric D. Hamlett; Erik Hjorth; Aurélie Ledreux; Anah Gilmore; Marianne Schultzberg; Ann Charlotte Granholm
    更新日期:2020-01-16
  • An update on human astrocytes and their role in development and disease
    Glia (IF 5.829) Pub Date : 2020-01-11
    Martina de Majo; Mark Koontz; David Rowitch; Erik M. Ullian
    更新日期:2020-01-13
  • Human iPSC‐derived microglia: A growing toolset to study the brain's innate immune cells
    Glia (IF 5.829) Pub Date : 2020-01-11
    Jonathan Hasselmann; Mathew Blurton‐Jones
    更新日期:2020-01-13
  • Dystrophic microglia in late‐onset Alzheimer's disease
    Glia (IF 5.829) Pub Date : 2020-01-10
    Wolfgang J. Streit; Habibeh Khoshbouei; Ingo Bechmann
    更新日期:2020-01-11
  • The mechanistic target of rapamycin pathway downregulates bone morphogenetic protein signaling to promote oligodendrocyte differentiation
    Glia (IF 5.829) Pub Date : 2020-01-06
    Isis M. Ornelas; Luipa Khandker; Stacey E. Wahl; Hirokazu Hashimoto; Wendy B. Macklin; Teresa L. Wood
    更新日期:2020-01-06
  • SorCS2 facilitates release of endostatin from astrocytes and controls post‐stroke angiogenesis
    Glia (IF 5.829) Pub Date : 2020-01-03
    Anna R. Malik; Janet Lips; Malgorzata Gorniak‐Walas; Diede W. M. Broekaart; Antonino Asaro; Melanie T. C. Kuffner; Christian J. Hoffmann; Majed Kikhia; Monika Dopatka; Philipp Boehm‐Sturm; Susanne Mueller; Ulrich Dirnagl; Eleonora Aronica; Christoph Harms; Thomas E. Willnow
    更新日期:2020-01-04
  • 2‐arachidonoylglycerol reduces chondroitin sulphate proteoglycan production by astrocytes and enhances oligodendrocyte differentiation under inhibitory conditions
    Glia (IF 5.829) Pub Date : 2020-01-02
    Ana Feliu; Leyre Mestre; Francisco J. Carrillo‐Salinas; V. Wee Yong; Miriam Mecha; Carmen Guaza
    更新日期:2020-01-02
  • Regulation of food intake by astrocytes in the brainstem dorsal vagal complex
    Glia (IF 5.829) Pub Date : 2019-12-27
    Alastair J. MacDonald; Fiona E. Holmes; Craig Beall; Anthony E. Pickering; Kate L. J. Ellacott
    更新日期:2019-12-27
  • Neuronal lactate levels depend on glia‐derived lactate during high brain activity in Drosophila
    Glia (IF 5.829) Pub Date : 2019-12-26
    Andrés González‐Gutiérrez; Andrés Ibacache; Andrés Esparza; Luis Felipe Barros; Jimena Sierralta
    更新日期:2019-12-27
  • Gpr126/Adgrg6 contributes to the terminal Schwann cell response at the neuromuscular junction following peripheral nerve injury
    Glia (IF 5.829) Pub Date : 2019-12-24
    Albina Jablonka‐Shariff; Chuieng‐Yi Lu; Katherine Campbell; Kelly R. Monk; Alison K. Snyder‐Warwick
    更新日期:2019-12-25
  • Connexin 43 deletion in astrocytes promotes CNS remyelination by modulating local inflammation
    Glia (IF 5.829) Pub Date : 2019-12-23
    Tao Li; Jianqin Niu; Guangdan Yu; Pascal Ezan; Chenju Yi; Xiaorui Wang; Annette Koulakoff; Xing Gao; Xianjun Chen; Juan C. Sáez; Christian Giaume; Lan Xiao
    更新日期:2019-12-23
  • A molecularly distinct subset of glioblastoma requires serum‐containing media to establish sustainable bona fide glioblastoma stem cell cultures
    Glia (IF 5.829) Pub Date : 2019-12-23
    Naga Prathyusha Maturi; E‐Jean Tan; Yuan Xie; Anders Sundström; Tobias Bergström; Yiwen Jiang; Lene Uhrbom
    更新日期:2019-12-23
  • Schwann cells orchestrate peripheral nerve inflammation through the expression of CSF1, IL‐34, and SCF in amyotrophic lateral sclerosis
    Glia (IF 5.829) Pub Date : 2019-12-20
    Emiliano Trias; Mariángeles Kovacs; Peter H. King; Ying Si; Yuri Kwon; Valentina Varela; Sofía Ibarburu; Ivan C. Moura; Olivier Hermine; Joseph S. Beckman; Luis Barbeito
    更新日期:2019-12-20
  • Activation of alpha‐2 adrenergic receptors stimulates GABA release by astrocytes
    Glia (IF 5.829) Pub Date : 2019-12-19
    Sergei G. Gaidin; Valery P. Zinchenko; Alexander I. Sergeev; Ilia Y. Teplov; Valentina N. Mal'tseva; Artem M. Kosenkov
    更新日期:2019-12-19
  • Ablation of neuronal ADAM17 impairs oligodendrocyte differentiation and myelination
    Glia (IF 5.829) Pub Date : 2019-12-18
    Evelien Fredrickx; Elisa Colombo; Paolo Canevazzi; Rosa La Marca; Marta Pellegatta; Giorgia Dina; Paola Podini; Klaus A. Nave; Angelo Quattrini; Carla Taveggia
    更新日期:2019-12-19
  • Transcriptional profiling of microglia; current state of the art and future perspectives
    Glia (IF 5.829) Pub Date : 2019-12-17
    Emma Gerrits; Yang Heng; Erik W. G. M. Boddeke; Bart J. L. Eggen
    更新日期:2019-12-18
  • Mutant C9orf72 human iPSC‐derived astrocytes cause non‐cell autonomous motor neuron pathophysiology
    Glia (IF 5.829) Pub Date : 2019-12-16
    Chen Zhao; Anna‐Claire Devlin; Amit K. Chouhan; Bhuvaneish T. Selvaraj; Maria Stavrou; Karen Burr; Veronica Brivio; Xin He; Arpan R. Mehta; David Story; Christopher E. Shaw; Owen Dando; Giles E. Hardingham; Gareth B. Miles; Siddharthan Chandran
    更新日期:2019-12-17
  • The role of chromatin remodeling complexes in Schwann cell development
    Glia (IF 5.829) Pub Date : 2019-12-14
    Franziska Fröb; Michael Wegner
    更新日期:2019-12-17
  • Bestrophin1‐mediated tonic GABA release from reactive astrocytes prevents the development of seizure‐prone network in kainate‐injected hippocampi
    Glia (IF 5.829) Pub Date : 2019-12-13
    Sudip Pandit; Chiranjivi Neupane; Junsung Woo; Ramesh Sharma; Min‐Ho Nam; Gyu‐Seung Lee; Min‐Hee Yi; Nara Shin; Dong Woon Kim; Hyunsill Cho; Byeong Hwa Jeon; Hyun‐Woo Kim; C. Justin Lee; Jin Bong Park
    更新日期:2019-12-13
  • Deletion of astrocytic BMAL1 results in metabolic imbalance and shorter lifespan in mice
    Glia (IF 5.829) Pub Date : 2019-12-13
    Olga Barca‐Mayo; Arjen J. Boender; Andrea Armirotti; Davide De Pietri Tonelli
    更新日期:2019-12-13
  • Microglial cell‐derived interleukin‐6 influences behavior and inflammatory response in the brain following traumatic brain injury
    Glia (IF 5.829) Pub Date : 2019-12-04
    Paula Sanchis, Olaya Fernández‐Gayol, Joel Vizueta, Gemma Comes, Carla Canal, Anna Escrig, Amalia Molinero, Mercedes Giralt, Juan Hidalgo
    更新日期:2019-12-04
  • Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer's disease
    Glia (IF 5.829) Pub Date : 2019-12-04
    Loukia Katsouri, Amy M. Birch, Alexander W. J. Renziehausen, Carolin Zach, Yahyah Aman, Hannah Steeds, Angela Bonsu, Emily O. C. Palmer, Nazanin Mirzaei, Miriam Ries, Magdalena Sastre
    更新日期:2019-12-04
  • mTOR‐mediated metabolic reprogramming shapes distinct microglia functions in response to lipopolysaccharide and ATP
    Glia (IF 5.829) Pub Date : 2019-12-03
    Yaling Hu, Weihao Mai, Lunhao Chen, Kelei Cao, Bin Zhang, Zhenjie Zhang, Yijun Liu, Huifang Lou, Shumin Duan, Zhihua Gao
    更新日期:2019-12-03
  • Glia of the human retina
    Glia (IF 5.829) Pub Date : 2019-12-03
    Andreas Reichenbach, Andreas Bringmann
    更新日期:2019-12-03
  • Activated microglia desialylate their surface, stimulating complement receptor 3‐mediated phagocytosis of neurons
    Glia (IF 5.829) Pub Date : 2019-11-27
    David H. Allendorf, Mar Puigdellívol, Guy C. Brown
    更新日期:2019-11-28
  • Platelet‐derived growth factor receptor α/glial fibrillary acidic protein expressing peritumoral astrocytes associate with shorter median overall survival in glioblastoma patients
    Glia (IF 5.829) Pub Date : 2019-11-26
    Lina Leiss, Alessandro Mega, Thomas Olsson Bontell, Monica Nistér, Anja Smits, Sara Corvigno, Mohummad Aminur Rahman, Per Øyvind Enger, Hrvoje Miletic, Arne Östman
    更新日期:2019-11-27
  • Disrupting insulin signaling in Schwann cells impairs myelination and induces a sensory neuropathy
    Glia (IF 5.829) Pub Date : 2019-11-23
    Amber R. Hackett, Amy Strickland, Jeffrey Milbrandt

    Although diabetic mice have been studied for decades, little is known about the cell type specific contributions to diabetic neuropathy (DN). Schwann cells (SCs) myelinate and provide trophic support to peripheral nervous system axons. Altered SC metabolism leads to myelin defects, which can be seen both in inherited and DNs. How SC metabolism is altered in DN is not fully understood, but it is clear that insulin resistance underlies impaired lipid metabolism in many cell types throughout the body via the phosphoinositide 3‐kinase/protein kinase b (PKB)/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Here, we created an insulin resistant SC by deleting both insulin receptor (INSR) and insulin‐like growth factor receptor 1 (IGF1R), to determine the role of this signaling pathway in development and response to injury in order to understand SC defects in DN. We found that myelin is thinner throughout development and adulthood in INSR/IGF1R Schwann cell specific knock out mice. The nerves of these mutant mice had reduced expression of key genes that mediate fatty acid and cholesterol synthesis due to reduced mTOR–sterol regulatory element‐binding protein signaling. In adulthood, these mice show sensory neuropathy phenotypes reminiscent of diabetic mice. Altogether, these data suggest that SCs may play an important role in DN and targeting their metabolism could lead to new therapies for DN.

    更新日期:2019-11-26
  • Differential effects of glucose deprivation on the survival of fetal versus adult neural stem cells‐derived oligodendrocyte precursor cells
    Glia (IF 5.829) Pub Date : 2019-11-22
    Vito Antonio Baldassarro, Alessandra Marchesini, Luciana Giardino, Laura Calzà
    更新日期:2019-11-22
  • Limited contribution of astroglial gap junction coupling to buffering of extracellular K+ in CA1 stratum radiatum
    Glia (IF 5.829) Pub Date : 2019-11-19
    Björn Breithausen, Steffen Kautzmann, Anne Boehlen, Christian Steinhäuser, Christian Henneberger
    更新日期:2019-11-20
  • Microglia and sexual differentiation of the developing brain: A focus on ontogeny and intrinsic factors
    Glia (IF 5.829) Pub Date : 2019-11-19
    Evan A. Bordt, Alexis M. Ceasrine, Staci D. Bilbo
    更新日期:2019-11-20
  • Bmal1‐deficiency affects glial synaptic coverage of the hippocampal mossy fiber synapse and the actin cytoskeleton in astrocytes
    Glia (IF 5.829) Pub Date : 2019-11-19
    Amira A. H. Ali, Beryl Schwarz‐Herzke, Astrid Rollenhagen, Max Anstötz, Martin Holub, Joachim Lübke, Christine R. Rose, Hans‐Joachim Schnittler, Charlotte von Gall
    更新日期:2019-11-20
  • Sox9 overexpression exerts multiple stage‐dependent effects on mouse spinal cord development
    Glia (IF 5.829) Pub Date : 2019-11-14
    Julia K. Vogel, Matthias Weider, Lisa A. Engler, Simone Hillgärtner, Christian Schmitt, Irm Hermans‐Borgmeyer, Michael Wegner
    更新日期:2019-11-14
  • Species differences in immune‐mediated CNS tissue injury and repair: A (neuro)inflammatory topic
    Glia (IF 5.829) Pub Date : 2019-11-14
    Luke M. Healy, Moein Yaqubi, Samuel Ludwin, Jack P. Antel
    更新日期:2019-11-14
  • LncRNA BC088259 promotes Schwann cell migration through Vimentin following peripheral nerve injury
    Glia (IF 5.829) Pub Date : 2019-11-13
    Chun Yao, Yanping Chen, Jing Wang, Tianmei Qian, Wei Feng, Yuanyuan Chen, Susu Mao, Bin Yu
    更新日期:2019-11-13
  • Role of astrocyte purinergic signaling in epilepsy
    Glia (IF 5.829) Pub Date : 2019-11-09
    Ljiljana Nikolic, Paola Nobili, Weida Shen, Etienne Audinat
    更新日期:2019-11-11
  • CNS myelin protein 36K regulates oligodendrocyte differentiation through Notch
    Glia (IF 5.829) Pub Date : 2019-11-08
    Bhuvaneswari Nagarajan, Alexander Harder, Anna Japp, Felix Häberlein, Enrico Mingardo, Henning Kleinert, Öznur Yilmaz, Angelika Zoons, Birgit Rau, Andrea Christ, Ulrich Kubitscheck, Britta Eiberger, Roger Sandhoff, Matthias Eckhardt, Dieter Hartmann, Benjamin Odermatt
    更新日期:2019-11-08
  • Epigenetic regulation of microglial phosphatidylinositol 3‐kinase pathway involved in long‐term potentiation and synaptic plasticity in rats
    Glia (IF 5.829) Pub Date : 2019-11-08
    Genevieve Saw, Kumar Krishna, Neelima Gupta, Tuck Wah Soong, Karthik Mallilankaraman, Sreedharan Sajikumar, S. Thameem Dheen
    更新日期:2019-11-08
  • The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination
    Glia (IF 5.829) Pub Date : 2019-11-07
    Elizabeth J. Thomason, Miguel Escalante, Donna J. Osterhout, Babette Fuss
    更新日期:2019-11-07
  • Sublamina‐specific organization of the blood brain barrier in the mouse olfactory nerve layer
    Glia (IF 5.829) Pub Date : 2019-11-07
    Antonia Beiersdorfer, Hartwig Wolburg, Janine Grawe, Anja Scheller, Frank Kirchhoff, Christian Lohr
    更新日期:2019-11-07
  • Microglia and sexual differentiation of the developing brain: A focus on extrinsic factors
    Glia (IF 5.829) Pub Date : 2019-11-06
    Jonathan W. VanRyzin, Ashley E. Marquardt, Lindsay A. Pickett, Margaret M. McCarthy
    更新日期:2019-11-06
  • Microglial expression of GAT‐1 in the cerebral cortex
    Glia (IF 5.829) Pub Date : 2019-11-06
    Giorgia Fattorini, Myriam Catalano, Marcello Melone, Carmela Serpe, Silvia Bassi, Cristina Limatola, Fiorenzo Conti
    更新日期:2019-11-06
  • NF‐E2‐related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin‐1 mutated Alzheimer's disease astrocytes
    Glia (IF 5.829) Pub Date : 2019-10-31
    Minna Oksanen, Ida Hyötyläinen, Kalevi Trontti, Taisia Rolova, Sara Wojciechowski, Marja Koskuvi, Matti Viitanen, Anna‐Liisa Levonen, Iiris Hovatta, Laurent Roybon, Šárka Lehtonen, Katja M. Kanninen, Riikka H. Hämäläinen, Jari Koistinaho

    Alzheimer's disease (AD) is a common dementia affecting a vast number of individuals and significantly impairing quality of life. Despite extensive research in animal models and numerous promising treatment trials, there is still no curative treatment for AD. Astrocytes, the most common cell type of the central nervous system, have been shown to play a role in the major AD pathologies, including accumulation of amyloid plaques, neuroinflammation, and oxidative stress. Here, we show that inflammatory stimulation leads to metabolic activation of human astrocytes and reduces amyloid secretion. On the other hand, the activation of oxidative metabolism leads to increased reactive oxygen species production especially in AD astrocytes. While healthy astrocytes increase glutathione (GSH) release to protect the cells, Presenilin‐1‐mutated AD patient astrocytes do not. Thus, chronic inflammation is likely to induce oxidative damage in AD astrocytes. Activation of NRF2, the major regulator of cellular antioxidant defenses, encoded by the NFE2L2 gene, poses several beneficial effects on AD astrocytes. We report here that the activation of NRF2 pathway reduces amyloid secretion, normalizes cytokine release, and increases GSH secretion in AD astrocytes. NRF2 induction also activates the metabolism of astrocytes and increases the utilization of glycolysis. Taken together, targeting NRF2 in astrocytes could be a potent therapeutic strategy in AD.

    更新日期:2019-11-01
  • Developmental stage‐specific role of Frs adapters as mediators of FGF receptor signaling in the oligodendrocyte lineage cells
    Glia (IF 5.829) Pub Date : 2019-10-31
    Miki Furusho, Akihiro Ishii, Jean M. Hebert, Rashmi Bansal

    FGF signaling is important for numerous cellular processes and produces diverse cellular responses. Our recent studies using mice conditionally lacking FGF‐Receptor‐1 (Fgfr1) or Fgfr2 during different stages of myelinogenesis revealed that Fgfr signaling is first required embryonically for the specification of oligodendrocyte progenitors (OPCs) and then later postnatally for the growth of the myelin sheath during active myelination but not for OPC proliferation, differentiation, or ensheathment of axons. What intracellular signal transduction pathways are recruited immediately downstream of Fgfrs and mediate these distinct developmentally regulated stage‐specific responses remain unclear. The adapter protein Fibroblast‐Growth‐Factor‐Receptor‐Substrate‐2 (Frs2) is considered a key immediate downstream target of Fgfrs. Therefore, here, we investigated the in vivo role of Frs adapters in the oligodendrocyte lineage cells, using a novel genetic approach where mice were engineered to disrupt binding of Frs2 to Fgfr1 or Fgfr2, thus specifically uncoupling Frs2 and Fgfr signaling. In addition, we used conditional mutants with complete ablation of Frs2 and Frs3. We found that Frs2 is required for specification of OPCs in the embryonic telencephalon downstream of Fgfr1. In contrast, Frs2 is largely dispensable for transducing Fgfr2‐mediated signals for the growth of the myelin sheath during postnatal myelination, implying the potential involvement of other adapters downstream of Fgfr2 for this function. Together, our data demonstrate a developmental stage‐specific function of Frs2 in the oligodendrocyte lineage cells. This contextual requirement of adapter proteins, downstream of Fgfrs, could partly explain the distinct responses elicited by the activation of Fgfrs during different stages of myelinogenesis.

    更新日期:2019-11-01
  • Juvenile mild traumatic brain injury elicits distinct spatiotemporal astrocyte responses
    Glia (IF 5.829) Pub Date : 2019-10-31
    Tifenn Clément, Jeong B. Lee, Aleksandra Ichkova, Beatriz Rodriguez‐Grande, Marie‐Line Fournier, Justine Aussudre, Michael Ogier, Elizabeth Haddad, Frederic Canini, Muriel Koehl, Djoher Nora Abrous, Andre Obenaus, Jerome Badaut

    Mild‐traumatic brain injury (mTBI) represents ~80% of all emergency room visits and increases the probability of developing long‐term cognitive disorders in children. To date, molecular and cellular mechanisms underlying post‐mTBI cognitive dysfunction are unknown. Astrogliosis has been shown to significantly alter astrocytes' properties following brain injury, potentially leading to significant brain dysfunction. However, such alterations have never been investigated in the context of juvenile mTBI (jmTBI). A closed‐head injury model was used to study jmTBI on postnatal‐day 17 mice. Astrogliosis was evaluated using glial fibrillary acidic protein (GFAP), vimentin, and nestin immunolabeling in somatosensory cortex (SSC), dentate gyrus (DG), amygdala (AMY), and infralimbic area (ILA) of prefrontal cortex in both hemispheres from 1 to 30 days postinjury (dpi). In vivo T2‐weighted‐imaging (T2WI) and diffusion tensor imaging (DTI) were performed at 7 and 30 dpi to examine tissue level structural alterations. Increased GFAP‐labeling was observed up to 30 dpi in the ipsilateral SSC, the initial site of the impact. However, vimentin and nestin expression was not perturbed by jmTBI. The morphology of GFAP positive cells was significantly altered in the SSC, DG, AMY, and ILA up to 7 dpi that some correlated with magnetic resonance imaging changes. T2WI and DTI values were significantly altered at 30 dpi within these brain regions most prominently in regions distant from the impact site. Our data show that jmTBI triggers changes in astrocytic phenotype with a distinct spatiotemporal pattern. We speculate that the presence and time course of astrogliosis may contribute to pathophysiological processes and long‐term structural alterations following jmTBI.

    更新日期:2019-11-01
  • Astrocytes follow ganglion cell axons to establish an angiogenic template during retinal development.
    Glia (IF 5.829) Pub Date : 2017-07-20
    Matthew L O'Sullivan,Vanessa M Puñal,Patrick C Kerstein,Joseph A Brzezinski,Tom Glaser,Kevin M Wright,Jeremy N Kay

    Immature astrocytes and blood vessels enter the developing mammalian retina at the optic nerve head and migrate peripherally to colonize the entire retinal nerve fiber layer (RNFL). Retinal vascularization is arrested in retinopathy of prematurity (ROP), a major cause of bilateral blindness in children. Despite their importance in normal development and ROP, the factors that control vascularization of the retina remain poorly understood. Because astrocytes form a reticular network that appears to provide a substrate for migrating endothelial cells, they have long been proposed to guide angiogenesis. However, whether astrocytes do in fact impose a spatial pattern on developing vessels remains unclear, and how astrocytes themselves are guided is unknown. Here we explore the cellular mechanisms that ensure complete retinal coverage by astrocytes and blood vessels in mouse. We find that migrating astrocytes associate closely with the axons of retinal ganglion cells (RGCs), their neighbors in the RNFL. Analysis of Robo1; Robo2 mutants, in which RGC axon guidance is disrupted, and Math5 (Atoh7) mutants, which lack RGCs, reveals that RGCs provide directional information to migrating astrocytes that sets them on a centrifugal trajectory. Without this guidance, astrocytes exhibit polarization defects, fail to colonize the peripheral retina, and display abnormal fine-scale spatial patterning. Furthermore, using cell type-specific chemical-genetic tools to selectively ablate astrocytes, we show that the astrocyte template is required for angiogenesis and vessel patterning. Our results are consistent with a model whereby RGC axons guide formation of an astrocytic network that subsequently directs vessel development.

    更新日期:2019-11-01
  • Expression of Nav1.6 sodium channels by Schwann cells at neuromuscular junctions: role in the motor endplate disease phenotype.
    Glia (IF 5.829) Pub Date : 2005-08-04
    Magali Musarella,Gisèle Alcaraz,Ghislaine Caillol,Jean-Louis Boudier,François Couraud,Amapola Autillo-Touati

    In addition to their role in action potential generation and fast synaptic transmission in neurons, voltage-dependent sodium channels can also be active in glia. Terminal Schwann cells (TSCs) wrap around the nerve terminal arborization at the neuromuscular junction, which they contribute to shape during development and in the postdenervation processes. Using fluorescent in situ hybridization (FISH), immunofluorescence, and confocal microscopy, we detected the neuronal Nav1.6 sodium channel transcripts and proteins in TSCs in normal adult rats and mice. Nav1.6 protein co-localized with the Schwann cell marker S-100 but was not detected in the SV2-positive nerve terminals. The med phenotype in mice is due to a mutation in the SCN8A gene resulting in loss of Nav1.6 expression. It leads to early onset in postnatal life of defects in neuromuscular transmission with minimal alteration of axonal conduction. Strikingly, in mutant mice, the nonmyelinated pre-terminal region of axons showed abundant sprouting at neuromuscular junctions, and most of the alpha-bungarotoxin-labeled endplates were devoid of S-100- or GFAP-positive TSCs. Using specific antibodies against the Nav1.2 and Nav1.6 sodium channels, ankyrin G and Caspr 1, and a pan sodium channel antibody, we found that a similar proportion of ankyrin G-positive nodes of Ranvier express sodium channels in mutant and wild-type animals and that nodal expression of Nav1.2 persists in med mice. Our data supports the hypothesis that the lack of expression of Nav1.6 in Schwann cells at neuromuscular junctions might play a role in the med phenotype.

    更新日期:2019-11-01
  • Inhibition of astrocyte FAK-JNK signaling promotes subventricular zone neurogenesis through CNTF.
    Glia (IF 5.829) Pub Date : 2018-12-01
    Cuihong Jia,Matthew P Keasey,Chiharu Lovins,Theo Hagg

    Astrocyte-derived ciliary neurotrophic factor (CNTF) promotes adult subventricular zone (SVZ) neurogenesis. We found that focal adhesion kinase (FAK) and JNK, but not ERK or P38, repress CNTF in vitro. Here, we defined the FAK-JNK pathway and its regulation of CNTF in mice, and the related leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), which promote stem cell renewal at the expense of neurogenesis. Intrastriatal injection of FAK inhibitor, FAK14, in adult male C57BL/6 mice reduced pJNK and increased CNTF expression in the SVZ-containing periventricular region. Injection of a JNK inhibitor increased CNTF without affecting LIF and IL-6, and increased SVZ proliferation and neuroblast formation. The JNK inhibitor had no effect in CNTF-/- mice, suggesting that JNK inhibits SVZ neurogenesis by repressing CNTF. Inducible deletion of FAK in astrocytes increased SVZ CNTF and neurogenesis, but not LIF and IL-6. Intrastriatal injection of inhibitors suggested that P38 reduces LIF and IL-6 expression, whereas ERK induces CNTF and LIF. Intrastriatal FAK inhibition increased LIF, possibly through ERK, and IL-6 through another pathway that does not involve P38. Systemic injection of FAK14 also inhibited JNK while increasing CNTF, but did not affect P38 and ERK activation, or LIF and IL-6 expression. Importantly, systemic FAK14 increased SVZ neurogenesis in wild-type C57BL/6 and CNTF+/+ mice, but not in CNTF-/- littermates, indicating that it acts by upregulating CNTF. These data show a surprising differential regulation of related cytokines and identify the FAK-JNK-CNTF pathway as a specific target in astrocytes to promote neurogenesis and possibly neuroprotection in neurological disorders.

    更新日期:2019-11-01
  • Manganese-induced downregulation of astroglial glutamine transporter SNAT3 involves ubiquitin-mediated proteolytic system.
    Glia (IF 5.829) Pub Date : 2010-08-26
    Marta Sidoryk-Wegrzynowicz,Eun-Sook Lee,Mingwei Ni,Michael Aschner

    SNAT3 is a major facilitator of glutamine (Gln) efflux from astrocytes, supplying Gln to neurons for neurotransmitter synthesis. Our previous investigations have shown that, in primary cortical astrocyte cultures, SNAT3 protein is degraded after exposure to manganese (Mn(2+)). The present studies were performed to identify the processes responsible for this effect. One of the well-established mechanisms for protein-level regulation is posttranslational modification via ubiquitination, which leads to the rapid degradation of proteins by the 26S proteasome pathway. Here, we show that astrocytic SNAT3 directly interacts with the ubiquitin ligase, Nedd4-2 (neural precursor cells expressed developmentally downregulated 4-2), and that Mn(2+) increases both Nedd4-2 mRNA and protein levels. Additionally, we have found that Mn(2+) exposure elevates astrocytic ubiquitin B mRNA expression, free ubiquitin protein levels, and total protein ubiquitination. Furthermore, Mn(2+) effectively decreases astrocytic mRNA expression and the phosphorylation of serum and glucocorticoid-inducible kinase, a regulatory protein, which, in the active phosphorylated form, is responsible for the phosphorylation and subsequent inactivation of Nedd4-2. Additional findings establish that Mn(2+) increases astrocytic caspase-like proteolytic proteasome activity and that the Mn(2+)-dependent degradation of SNAT3 protein is blocked by the proteasome inhibitors, N-acetyl-leu-leu-norleucinal and lactacystin. Combined, these results demonstrate that Mn(2+)-induced SNAT3 protein degradation and the dysregulation of Gln homeostasis in primary astrocyte cultures proceeds through the ubiquitin-mediated proteolytic system.

    更新日期:2019-11-01
  • Interferons in the central nervous system: a few instruments play many tunes.
    Glia (IF 5.829) Pub Date : 2014-03-04
    Trevor Owens,Reza Khorooshi,Agnieszka Wlodarczyk,Nasrin Asgari

    Interferons (IFNs) are implicated as an important component of the innate immune system influencing viral infections, inflammation, and immune surveillance. We review here the complex biological activity of IFNs in the central nervous system (CNS) and associated glial–immune interactions, with focus specifically on the Type I IFNs in physiological and pathological conditions. IFN-α and IFN-β are the predominant Type I IFNs in the CNS. They are produced in the CNS by glial cells, mostly microglia and astrocytes, as well as by neurons. A variety of mechanisms stimulate IFN production in glial cells, including innate stimuli from Toll-like and other receptors, which can recognize endogenous entities, as well as pathogens. We will review evidence that differential signaling by IFN-α versus IFN-β through the common heterodimeric receptor IFNAR is the basis for CNS-selective Type I IFN response, and the capacity of CNS glial cells to produce and respond to Type I IFN. Differential signaling outcomes of IFN-α and IFN-β, which have been ascribed to differential affinity for IFNAR1 and IFNAR2, determine whether Type I IFN exert pathogenic or protective roles in the CNS. These points will be discussed with reference to selected neurological diseases, and effects of Type I IFN on the integrity of the blood–brain barrier.

    更新日期:2019-11-01
  • Molecular evolution of myelin basic protein, an abundant structural myelin component.
    Glia (IF 5.829) Pub Date : 2013-09-17
    Schanila Nawaz,Jörn Schweitzer,Olaf Jahn,Hauke B Werner

    Rapid nerve conduction in jawed vertebrates is facilitated by the myelination of axons, which evolved in ancient cartilaginous fish. We aim to understand the coevolution of myelin and the major myelin proteins. We found that myelin basic protein (MBP) derived from living cartilaginous fish (sharks and rays) associated with the plasma membrane of glial cells similar to the phosphatidylinositol (4,5)-bisphosphate (PIP₂)-binding marker PH-PLCδ1, and that ionomycin-induced PIP₂-hydrolysis led to its cellular redistribution. We identified two paralogous mbp genes in multiple teleost species, consistent with a genome duplication at the root of the teleost clade. Zebrafish mbpb is organized in a complex transcription unit together with the unrelated gene-of-the-oligodendrocyte-lineage (golli) while mbpa does not encode GOLLI. Moreover, the embryonic expression of mbpa and mbpb differed, indicating functional specialization after duplication. However, both mbpa and mbpb-mRNAs were detected in mature oligodendrocytes and Schwann cells, MBPa and MBPb were mass spectrometrically identified in zebrafish myelin, both associated with the plasma membrane via PIP₂, and the ratio of nonsynonymous to synonymous nucleotide-substitution rates (Ka/Ks) was low. Together, this indicates selective pressure to conserve many aspects of the cellular expression and function of MBP across vertebrate species. We propose that the PIP₂-binding function of MBP is evolutionarily old and that its emergence in ancient gnathostomata provided glial cells with the competence to myelinate.

    更新日期:2019-11-01
  • Cthrc1 is a negative regulator of myelination in Schwann cells.
    Glia (IF 5.829) Pub Date : 2012-03-02
    Caroline Apra,Laurence Richard,Fanny Coulpier,Corinne Blugeon,Pascale Gilardi-Hebenstreit,Jean-michel Vallat,Volkhard Lindner,Patrick Charnay,Laurence Decker

    The analysis of the molecular mechanisms involved in the initial interaction between neurons and Schwann cells is a key issue in understanding the myelination process. We recently identified Cthrc1 (Collagen triple helix repeat containing 1) as a gene upregulated in Schwann cells upon interaction with the axon. Cthrc1 encodes a secreted protein previously shown to be involved in migration and proliferation in different cell types. We performed a functional analysis of Cthrc1 in Schwann cells by loss-of- and gain-of-function approaches using RNA interference knockdown in cell culture and a transgenic mouse line that overexpresses the gene. This work establishes that Cthrc1 enhances Schwann cell proliferation but prevents myelination. In particular, time-course analysis of myelin formation intransgenic animals reveals that overexpression of Cthrc1 in Schwann cells leads to a delay in myelin formation with cells maintaining a proliferative state. Our data, therefore, demonstrate that Cthrc1 plays a negative regulatory role, fine-tuning the onset of peripheral myelination.

    更新日期:2019-11-01
  • The brain tumor microenvironment.
    Glia (IF 5.829) Pub Date : 2012-03-02
    Nikki A Charles,Eric C Holland,Richard Gilbertson,Rainer Glass,Helmut Kettenmann

    High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells maybe the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells,microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology.In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells,which can contribute up to 30% of a brain tumor mass,play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete.

    更新日期:2019-11-01
  • Three-dimensional relationships between perisynaptic astroglia and human hippocampal synapses.
    Glia (IF 5.829) Pub Date : 2009-11-13
    Mark R Witcher,Yong D Park,Mark R Lee,Suash Sharma,Kristen M Harris,Sergei A Kirov

    Perisynaptic astroglia are critical for normal synaptic development and function. Little is known, however, about perisynaptic astroglia in the human hippocampus. When mesial temporal lobe epilepsy (MTLE) is refractory to medication, surgical removal is required for seizure quiescence. To investigate perisynaptic astroglia in human hippocampus, we recovered slices for several hours in vitro from three surgical specimens and then quickly fixed them to achieve high-quality ultrastructure. Histological samples from each case were found to have mesial temporal sclerosis with Blumcke Type 1a (mild, moderate) or 1b (severe) pathology. Quantitative analysis through serial section transmission electron microscopy in CA1 stratum radiatum revealed more synapses in the mild (10/10 microm(3)) than the moderate (5/10 microm(3)) or severe (1/10 microm(3)) cases. Normal spines occurred in mild and moderate cases, but a few multisynaptic spines were all that remained in the severe case. Like adult rat hippocampus, perisynaptic astroglial processes were preferentially associated with larger synapses in the mild and moderate cases, but rarely penetrated the cluster of axonal boutons surrounding multisynaptic spines. Synapse perimeters were only partially surrounded by astroglial processes such that all synapses had some access to substances in the extracellular space, similar to adult rat hippocampus. Junctions between astroglial processes were observed more frequently in moderate than mild case, but were obscured by densely packed intermediate filaments in astroglial processes of the severe case. These findings suggest that perisynaptic astroglial processes associate with synapses in human hippocampus in a manner similar to model systems and are disrupted by severe MTLE pathology.

    更新日期:2019-11-01
  • APP knockout attenuates microglial activation and enhances neuron survival in substantia nigra compacta after axotomy.
    Glia (IF 5.829) Pub Date : 2002-04-12
    Lorraine A DeGiorgio,Yoshinori Shimizu,Hong S Chun,Byung-Pil Cho,Shuei Sugama,Tong H Joh,Bruce T Volpe

    Focal microglial activation and progressive dopaminergic neurodegeneration in substantia nigra compacta (SNc) have characterized Parkinson's disease (PD). We have hypothesized that the microglial response may be provoked by molecular signals from chronically stressed SNc neurons. To test whether amyloid precursor protein (APP) could serve as such a signal, we evaluated microglial activation in SN after unilateral transection of the medial forebrain bundle (MFB) in mice either wild-type (WT) or null (KO) for APP. WT and KO mice displayed comparable microglial response at the MFB transection site. In WT mice microglial activation was first apparent in the ipsilateral SN at 3 days postlesion (dpl), marked by morphological change and increased isolectin immunoreactivity. The microglial response intensified at 7 dpl and persisted in the medial nigra through 14 dpl. In contrast, in KO mice activated microglia appeared predominantly at 7 dpl, with little activation at 3 dpl and none at 14 dpl. Neuron number in affected WT SNc at 14 dpl was significantly reduced compared with loss in affected KO SNc. The delayed and limited local microglial activation and increased neuron survival in response to distal axotomy of SNc neurons in APP KO mice are consistent with the important role APP in neuronal stress responses in vivo.

    更新日期:2019-11-01
  • Expression of the complement C3a and C5a receptors after permanent focal ischemia: An alternative interpretation.
    Glia (IF 5.829) Pub Date : 2002-04-12
    Scott R Barnum,Robert S Ames,Peter R Maycox,Sarah J Hadingham,Jackie Meakin,David Harrison,Andrew A Parsons

    The receptors for the complement anaphylatoxins C3a and C5a are expressed by glial cells and neurons in normal and inflamed brain. Previous studies demonstrated modest elevations in mRNA expression of these receptors in a model of focal cerebral ischemia. Using a similar model system for both mice and rats, we report markedly different patterns of anaphylatoxin receptor mRNA expression in cerebral ischemia. C5a receptor expression was dramatically elevated within 3 h after middle cerebral artery occlusion, while C3aR expression was reduced to 25% of control animals. By 24 h post-occlusion, expression of both receptors was higher than at any other time point examined. This increased expression at late time points after occlusion is most likely the result of massive infiltration of leukocytes expressing the receptors. We also observed increased receptor mRNA expression in sham-operated animals, indicating that the procedures used for arterial occlusion affects mechanisms regulating receptor expression. This latter result highlights the importance of including this important control group in ischemic model systems for proper interpretation of changes in gene expression.

    更新日期:2019-11-01
  • Modelling large areas of demyelination in the rat reveals the potential and possible limitations of transplanted glial cells for remyelination in the CNS.
    Glia (IF 5.829) Pub Date : 2002-04-12
    W F Blakemore,D M Chari,J M Gilson,A J Crang

    Transplantation of myelin-forming glial cells may provide a means of achieving remyelination in situations in which endogenous remyelination fails. For this type of cell therapy to be successful, cells will have to migrate long distances in normal tissue and within areas of demyelination. In this study, 40 Gy of X-irradiation was used to deplete tissue of endogenous oligodendrocyte progenitors (OPCs). By transplanting neonatal OPCs into OPC-depleted tissue, we were able to examine the speed with which neonatal OPCs repopulate OPC-depleted tissue. Using antibodies to NG-2 proteoglycan and in situ hybridisation to detect platelet-derived growth factor alpha-receptor Ralpha (PDGFRalpha) mRNA to visualise OPCs, we were able to show that neonatal OPCs repopulate OPC-depleted normal tissue 3-5 times more rapidly than endogenous OPCs. Transplanted neonatal OPCs restore OPC densities to near-normal values and when demyelinating lesions were made in tissue into which transplanted OPCs had been incorporated 1 month previously, we were able to show that the transplanted cells retain a robust ability to remyelinate axons after their integration into host tissue. In order to model the situation that would exist in a large OPC-depleted area of demyelination such as may occur in humans; we depleted tissue of its endogenous OPC population and placed focal demyelinating lesions at a distance (< or =1 cm) from a source of neonatal OPCs. In this situation, cells would have to repopulate depleted tissue in order to reach the area of demyelination. As the repopulation process would take time, this model allowed us to examine the consequences of delaying the interaction between OPCs and demyelinated axons on remyelination. Using this approach, we have obtained data that suggest that delaying the time of the interaction between OPCs and demyelinated axons restricts the expression of the remyelinating potential of transplanted OPCs.

    更新日期:2019-11-01
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