| 1. |
- Cho, Kin-Sang, et al.
(författare)
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Re-establishing the regenerative potential of central nervous system axons in postnatal mice.
- 2005
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Ingår i: Journal of cell science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 118:Pt 5, s. 863-72
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Tidskriftsartikel (refereegranskat)abstract
- At a certain point in development, axons in the mammalian central nervous system lose their ability to regenerate after injury. Using the optic nerve model, we show that this growth failure coincides with two developmental events: the loss of Bcl-2 expression by neurons and the maturation of astrocytes. Before postnatal day 4, when astrocytes are immature, overexpression of Bcl-2 alone supported robust and rapid optic nerve regeneration over long distances, leading to innervation of brain targets by day 4 in mice. As astrocytes matured after postnatal day 4, axonal regeneration was inhibited in mice overexpressing Bcl-2. Concurrent induction of Bcl-2 and attenuation of reactive gliosis reversed the failure of CNS axonal re-elongation in postnatal mice and led to rapid axonal regeneration over long distances and reinnervation of the brain targets by a majority of severed optic nerve fibers up to 2 weeks of age. These results suggest that an early postnatal downregulation of Bcl-2 and post-traumatic reactive gliosis are two important elements of axon regenerative failure in the CNS.
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| 2. |
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| 3. |
- Hultman, Karin, 1980, et al.
(författare)
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Retinoids and activation of PKC induce tissue-type plasminogen activator expression and storage in human astrocytes.
- 2008
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Ingår i: Journal of thrombosis and haemostasis : JTH. - : Elsevier BV. - 1538-7836. ; 6:10, s. 1796-803
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Emerging data demonstrate important roles for tissue-type plasminogen activator (t-PA) in the central nervous system (CNS). In contrast to endothelial cells, little is known about the regulation of t-PA gene expression and secretion in astrocytes. OBJECTIVES: The aims of the present study were to investigate whether t-PA gene expression is regulated by retinoids and the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) in human astrocytes, and to study whether t-PA is stored and subject to regulated release from these cells, as with endothelial cells. METHODS: Native human astrocytes were treated with RA and/or PMA. mRNA was quantified by real-time RT-PCR and protein secretion determined by ELISA. Intracellular t-PA immunoreactivity in astrocytes was examined by immunocyto- and histochemistry. RESULTS: RA and/or PMA induced a time-dependent increase in t-PA mRNA and protein levels in astrocytes, reaching 10-fold after combined treatment. This was associated with increased amounts of t-PA storage in intracellular granular structures. Both forskolin and histamine induced regulated release of t-PA. The presence of t-PA in reactive astrocytes was confirmed in human brain tissue. CONCLUSIONS: These data show that RA and PKC activation induce a strong up-regulation of t-PA expression in astrocytes, and increased intracellular storage pools. Moreover, a regulated release of t-PA can be induced from these cells. This raises the possibility that astrocytes contribute to the regulation of extracellular t-PA levels in the CNS.
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| 4. |
- Jing, R., et al.
(författare)
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Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with vimentin and GFAP intermediate filament networks
- 2007
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Ingår i: J Cell Sci. - : The Company of Biologists. - 0021-9533. ; 120:Pt 7, s. 1267-77
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Tidskriftsartikel (refereegranskat)abstract
- Immature astrocytes and astrocytoma cells contain synemin and three other intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), vimentin and nestin. Here, we show that, after neurotrauma, reactive astrocytes produce synemin and thus propose synemin as a new marker of reactive astrocytes. Comparison of synemin mRNA and protein levels in brain tissues and astrocyte cultures from wild-type, Vim(-)(/)(-) and Gfap(-)(/)(-)Vim(-)(/)(-) mice showed that in the absence of vimentin, synemin protein was undetectable although synemin mRNA was present at wild-type levels. By contrast, in Gfap(-)(/)(-) astrocytes, synemin protein and mRNA levels, as well as synemin incorporation into vimentin IFs, were unaltered. Biochemical assays with purified proteins suggested that synemin interacts with GFAP IFs like an IF-associated protein rather than like a polymerization partner, whereas the opposite was true for synemin interaction with vimentin. In transfection experiments, synemin did not incorporate into normal, filamentous GFAP networks, but integrated into vimentin and GFAP heteropolymeric networks. Thus, alongside GFAP, vimentin and nestin, reactive astrocytes contain synemin, whose accumulation is suppressed post-transcriptionally in the absence of a polymerization partner. In astrocytes, this partner is vimentin and not GFAP, which implies a functional difference between these two type III IF proteins.
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| 5. |
- Li, Lizhen, 1977, et al.
(författare)
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Protective role of reactive astrocytes in brain ischemia.
- 2008
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 28:3, s. 468-81
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Tidskriftsartikel (refereegranskat)abstract
- Reactive astrocytes are thought to protect the penumbra during brain ischemia, but direct evidence has been lacking due to the absence of suitable experimental models. Previously, we generated mice deficient in two intermediate filament (IF) proteins, glial fibrillary acidic protein (GFAP) and vimentin, whose upregulation is the hallmark of reactive astrocytes. GFAP(-/-)Vim(-/-) mice exhibit attenuated posttraumatic reactive gliosis, improved integration of neural grafts, and posttraumatic regeneration. Seven days after middle cerebral artery (MCA) transection, infarct volume was 210 to 350% higher in GFAP(-/-)Vim(-/-) than in wild-type (WT) mice; GFAP(-/-), Vim(-/-) and WT mice had the same infarct volume. Endothelin B receptor (ET(B)R) immunoreactivity was strong on cultured astrocytes and reactive astrocytes around infarct in WT mice but undetectable in GFAP(-/-)Vim(-/-) astrocytes. In WT astrocytes, ET(B)R colocalized extensively with bundles of IFs. GFAP(-/-)Vim(-/-) astrocytes showed attenuated endothelin-3-induced blockage of gap junctions. Total and glutamate transporter-1 (GLT-1)-mediated glutamate transport was lower in GFAP(-/-)Vim(-/-) than in WT mice. DNA array analysis and quantitative real-time PCR showed downregulation of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue plasminogen activator. Thus, reactive astrocytes have a protective role in brain ischemia, and the absence of astrocyte IFs is linked to changes in glutamate transport, ET(B)R-mediated control of gap junctions, and PAI-1 expression.
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| 6. |
- Mignot, Cyril, et al.
(författare)
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Dynamics of mutated GFAP aggregates revealed by real-time imaging of an astrocyte model of Alexander disease.
- 2007
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Ingår i: Experimental cell research. - : Elsevier BV. - 0014-4827. ; 313:13, s. 2766-79
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Tidskriftsartikel (refereegranskat)abstract
- Alexander disease (AxD) is a rare neurodegenerative disorder characterized by large cytoplasmic aggregates in astrocytes and myelin abnormalities and caused by dominant mutations in the gene encoding glial fibrillary acidic protein (GFAP), the main intermediate filament protein in astrocytes. We tested the effects of three mutations (R236H, R76H and L232P) associated with AxD in cells transiently expressing mutated GFAP fused to green fluorescent protein (GFP). Mutated GFAP-GFP expressed in astrocytes formed networks or aggregates similar to those found in the brains of patients with the disease. Time-lapse recordings of living astrocytes showed that aggregates of mutated GFAP-GFP may either disappear, associated with cell survival, or coalesce in a huge juxtanuclear structure associated with cell death. Immunolabeling of fixed cells suggested that this gathering of aggregates forms an aggresome-like structure. Proteasome inhibition and immunoprecipitation assays revealed mutated GFAP-GFP ubiquitination, suggesting a role of the ubiquitin-proteasome system in the disaggregation process. In astrocytes from wild-type-, GFAP-, and vimentin-deficient mice, mutated GFAP-GFP aggregated or formed a network, depending on qualitative and quantitative interactions with normal intermediate filament partners. Particularly, vimentin displayed an anti-aggregation effect on mutated GFAP. Our data indicate a dynamic and reversible aggregation of mutated GFAP, suggesting that therapeutic approaches may be possible.
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| 7. |
- Nakazawa, Toru, et al.
(författare)
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Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin.
- 2007
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Ingår i: Investigative ophthalmology & visual science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 48:6, s. 2760-8
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterize the reactions of retinal glial cells (astrocytes and Müller cells) to retinal injury in mice that lack glial fibrillary acidic protein (GFAP) and vimentin (GFAP-/-Vim-/-) and to determine the role of glial cells in retinal detachment (RD)-induced photoreceptor degeneration. METHODS: RD was induced by subretinal injection of sodium hyaluronate in adult wild-type (WT) and GFAP-/-Vim-/- mice. Astroglial reaction and subsequent monocyte recruitment were quantified by measuring extracellular signal-regulated kinase (Erk) and c-fos activation and the level of expression of chemokine monocyte chemoattractant protein (MCP)-1 and by counting monocytes/microglia in the detached retinas. Immunohistochemistry, immunoblotting, real-time quantitative polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used. RD-induced photoreceptor degeneration was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and measurement of outer nuclear layer (ONL) thickness. RESULTS: RD-induced reactive gliosis, characterized by GFAP and vimentin upregulation, Erk and c-fos activation, MCP-1 induction, and increased monocyte recruitment in WT mice. Absence of GFAP and vimentin effectively attenuated reactive responses of retinal glial cells and monocyte infiltration. As a result, detached retinas of GFAP-/-Vim-/- mice exhibited significantly reduced numbers of TUNEL-positive photoreceptor cells and increased ONL thickness compared with those of WT mice. CONCLUSIONS: The absence of GFAP and vimentin attenuates RD-induced reactive gliosis and, subsequently, limits photoreceptor degeneration. Results of this study indicate that reactive retinal glial cells contribute critically to retinal damage induced by RD and provide a new avenue for limiting photoreceptor degeneration associated with RD and other retinal diseases or damage.
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| 8. |
- Nilsson, Michael, 1962, et al.
(författare)
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Enriched environment and astrocytes in central nervous system regeneration.
- 2007
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Ingår i: Journal of rehabilitation medicine : official journal of the UEMS European Board of Physical and Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977. ; 39:5, s. 345-52
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Tidskriftsartikel (refereegranskat)abstract
- Rehabilitation medicine is entering a new era, based on the knowledge that the central nervous system has a substantial capacity for repair and regeneration. This capacity is used in 3 distinct but overlapping situations: (i) routine housekeeping throughout life (i.e. taking care of normal wear-and-tear); (ii) older age, when functional reserves of various kinds are depleted, resulting in cognitive, motor, and other deficits; and (iii) contexts in which a neurological deficit reflects an acute or chronic pathological process, such as neurotrauma, stroke, or neurodegenerative disease. The positive message here is two-fold. First, some aspects of regeneration occur even in the adult and ageing brain and spinal cord, and we are starting to unravel the underlying molecular mechanisms. Secondly, novel therapeutic approaches and targets are emerging that will substantially increase the efficiency and efficacy of rehabilitation and will transform rehabilitation into a discipline focusing both on its traditional domain and on prevention, ultimately across all the age categories. This review attempts to sum up the present knowledge about an enriched environment, currently the single most efficient plasticity- and regeneration-promoting paradigm. It also summarizes research showing that astrocytes - considered only years ago merely to nurse and support neurones - are a novel and highly interesting target for regenerative strategies in the brain and spinal cord.
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| 9. |
- Pekny, Milos, 1965, et al.
(författare)
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Astrocyte activation and reactive gliosis.
- 2005
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Ingår i: Glia. - : Wiley. - 0894-1491 .- 1098-1136. ; 50:4, s. 427-34
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes become activated (reactive) in response to many CNS pathologies, such as stroke, trauma, growth of a tumor, or neurodegenerative disease. The process of astrocyte activation remains rather enigmatic and results in so-called "reactive gliosis," a reaction with specific structural and functional characteristics. In stroke or in CNS trauma, the lesion itself, the ischemic environment, disrupted blood-brain barrier, the inflammatory response, as well as in metabolic, excitotoxic, and in some cases oxidative crises--all affect the extent and quality of reactive gliosis. The fact that astrocytes function as a syncytium of interconnected cells both in health and in disease, rather than as individual cells, adds yet another dimension to this picture. This review focuses on several aspects of astrocyte activation and reactive gliosis and discusses its possible roles in the CNS trauma and ischemia. Particular emphasis is placed on the lessons learnt from mouse genetic models in which the absence of intermediate filament proteins in astrocytes leads to attenuation of reactive gliosis with distinct pathophysiological and clinical consequences.
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| 10. |
- Pekny, Milos, 1965, et al.
(författare)
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GFAP and astrocyte intermediate filaments
- 2006
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Ingår i: The Handbook of Neurochemistry and Molecular Neurobiology. - : Springer Verlag.
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 11. |
- Pekny, Milos, 1965, et al.
(författare)
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Intermediate filaments and stress.
- 2007
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Ingår i: Experimental cell research. - : Elsevier BV. - 0014-4827. ; 313:10, s. 2244-54
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Tidskriftsartikel (refereegranskat)abstract
- Before we can explain why so many closely related intermediate filament genes have evolved in vertebrates, while maintaining such dramatically tissue specific expression, we need to understand their function. The best evidence for intermediate filament function comes from observing the consequences of mutation and mis-expression, primarily in human tissues. Mostly these observations suggest that intermediate filaments are important in allowing individual cells, the tissues and whole organs to cope with various types of stress, in health and disease. Exactly how they do this is unclear and many aspects of cell dysfunction have been associated with intermediate filaments to date. In particular, it is still not clear whether the non-mechanical functions now being attributed to intermediate filaments are primary functions of these structural proteins, or secondary consequences of their function to respond to mechanical stress. We discuss selected situations in which responses to stress are clearly influenced by intermediate filaments.
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| 12. |
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| 13. |
- Pekny, Milos, 1965, et al.
(författare)
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The role of astrocytes and complement system in neural plasticity.
- 2007
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Ingår i: International review of neurobiology. - 0074-7742. ; 82, s. 95-111
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Forskningsöversikt (refereegranskat)abstract
- In neurotrauma, brain ischemia or neurodegenerative diseases, astrocytes become reactive (which is known as reactive gliosis) and this is accompanied by an altered expression of many genes. Two cellular hallmarks of reactive gliosis are hypertrophy of astrocyte processes and the upregulation of the part of the cytoskeleton known as intermediate filaments, which are composed of nestin, vimentin, and GFAP. Our aim has been to better understand the function of reactive astrocytes in CNS diseases. Using mice deficient for astrocyte intermediate filaments (GFAP(-/-)Vim(-/-)), we were able to attenuate reactive gliosis and slow down the healing process after neurotrauma. We demonstrated the key role of reactive astrocytes in neurotrauma-at an early stage after neurotrauma, reactive astrocytes have a neuroprotective effect; at a later stage, they facilitate the formation of posttraumatic glial scars and inhibit CNS regeneration, specifically, they seem to compromise neural graft survival and integration, reduce the extent of synaptic regeneration, inhibit neurogenesis in the old age, and inhibit regeneration of severed CNS axons. We propose that reactive astrocytes are the future target for the therapeutic strategies promoting regeneration and plasticity in the brain and spinal cord in various disease conditions. Through its involvement in inflammation, opsonization, and cytolysis, complement protects against infectious agents. Although most of the complement proteins are synthesized in CNS, the role of the complement system in the normal or ischemic CNS remains unclear. Complement activiation in the CNS has been generally considered as contributing to tissue damage. However, growing body of evidence suggests that complement may be a physiological neuroprotective mechanism as well as it may participate in maintenance and repair of the adult brain.
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| 14. |
- Potokar, Maja, et al.
(författare)
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Cytoskeleton and vesicle mobility in astrocytes.
- 2007
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Ingår i: Traffic (Copenhagen, Denmark). - : Wiley. - 1398-9219. ; 8:1, s. 12-20
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Tidskriftsartikel (refereegranskat)abstract
- Exocytotic vesicles in astrocytes are increasingly viewed as essential in astrocyte-to-neuron communication in the brain. In neurons and excitable secretory cells, delivery of vesicles to the plasma membrane for exocytosis involves an interaction with the cytoskeleton, in particular microtubules and actin filaments. Whether cytoskeletal elements affect vesicle mobility in astrocytes is unknown. We labeled single vesicles with fluorescent atrial natriuretic peptide and monitored their mobility in rat astrocytes with depolymerized microtubules, actin, and intermediate filaments and in mouse astrocytes deficient in the intermediate filament proteins glial fibrillary acidic protein and vimentin. In astrocytes, as in neurons, microtubules participated in directional vesicle mobility, and actin filaments played an important role in this process. Depolymerization of intermediate filaments strongly affected vesicle trafficking and in their absence the fraction of vesicles with directional mobility was reduced.
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| 15. |
- Rahpeymai Bogestål, Yalda, 1977, et al.
(författare)
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Signaling through C5aR is not involved in basal neurogenesis.
- 2007
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Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012 .- 1097-4547. ; 85:13, s. 2892-7
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Tidskriftsartikel (refereegranskat)abstract
- The complement system, an important part of the innate immune system, provides protection against invading pathogens, in part through its proinflammatory activities. Although most complement proteins are synthesized locally in the brain and the relevant complement receptors are expressed on resident brain cells, little is known about brain-specific role(s) of the complement system. C3a and C5a, complement-derived peptides with anaphylatoxic properties, have been implicated in noninflammatory functions, such as tissue regeneration and neuroprotection. Recently, we have shown that signaling through C3a receptor (C3aR) is involved in the regulation of neurogenesis. In the present study, we assessed basal neurogenesis in mice lacking C5a receptor (C5aR(-/-)) and mice expressing C3a and C5a, respectively in the CNS under the control of glial fibrillary acidic protein (GFAP) promoter (C3a/GFAP and C5a/GFAP, respectively) and thus without the requirement for complement activation. We did not observe any difference among C5aR(-/-), C3a/GFAP and C5a/GFAP mice and their respective controls in the number of newly formed neuroblasts and newly formed neurons in the subventricular zone (SVZ) of lateral ventricles and hippocampal dentate gyrus, the two neurogenic niches in the adult brain, or the olfactory bulb, the final destination of new neurons formed in the SVZ. Our results indicate that signaling through C5aR is not involved in basal neurogenesis in adult mice and that basal neurogenesis in adult C3a/GFAP and C5a/GFAP mice is not altered. (c) 2007 Wiley-Liss, Inc.
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| 16. |
- Rahpeymai, Yalda, 1977, et al.
(författare)
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Complement: a novel factor in basal and ischemia-induced neurogenesis.
- 2006
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Ingår i: The EMBO journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 25:6, s. 1364-74
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Tidskriftsartikel (refereegranskat)abstract
- Through its involvement in inflammation, opsonization, and cytolysis, the complement protects against infectious agents. Although most of the complement proteins are synthesized in the central nervous system (CNS), the role of the complement system in the normal or ischemic CNS remains unclear. Here we demonstrate for the first time that neural progenitor cells and immature neurons express receptors for complement fragments C3a and C5a (C3a receptor (C3aR) and C5a receptor). Mice that are deficient in complement factor C3 (C3(-/-)) lack C3a and are unable to generate C5a through proteolytic cleavage of C5 by C5-convertase. Intriguingly, basal neurogenesis is decreased both in C3(-/-) mice and in mice lacking C3aR or mice treated with a C3aR antagonist. The C3(-/-) mice had impaired ischemia-induced neurogenesis both in the subventricular zone, the main source of neural progenitor cells in adult brain, and in the ischemic region, despite normal proliferative response and larger infarct volumes. Thus, in the adult mammalian CNS, complement activation products promote both basal and ischemia-induced neurogenesis.
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| 17. |
- Shinjyo, Noriko, et al.
(författare)
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Complement-derived anaphylatoxin C3a regulates in vitro differentiation and migration of neural progenitor cells.
- 2009
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Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 27:11, s. 2824-32
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Tidskriftsartikel (refereegranskat)abstract
- Anaphylatoxin C3a is a third complement component (C3)-derived peptide, the multiple functions of which range from stimulation of inflammation to neuroprotection. In a previous study, we have shown that signaling through C3a receptor positively regulates in vivo neurogenesis in adult mouse brain. Here, we studied the direct effects of C3a on adult mouse whole brain-derived neural progenitor cells (NPCs) in vitro. Our results demonstrate that NPCs bind C3a in a specific and reversible manner and that C3a stimulates neuronal differentiation of NPCs. Furthermore, C3a stimulated the migration of NPCs induced by low concentrations of stromal cell-derived factor (SDF)-1alpha, whereas it inhibited NPC migration at high concentration of SDF-1alpha. In the same manner, C3a modulated SDF-1alpha-induced extracellular-signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation in these cells. In addition, C3a had inhibitory effect on SDF-1alpha-induced neuronal differentiation of NPCs. These data show that C3a modulates SDF-1alpha-induced differentiation and migration of these cells, conceivably through the regulation of ERK1/2 phosphorylation. Our results provide the first evidence that C3a regulates neurogenesis by directly affecting the fate and properties of NPCs.
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| 18. |
- Sihlbom, Carina, 1973, et al.
(författare)
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14-3-3 expression in denervated hippocampus after entorhinal cortex lesion assessed by culture-derived isotope tags in quantitative proteomics.
- 2007
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Ingår i: Journal of proteome research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:9, s. 3491-500
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Tidskriftsartikel (refereegranskat)abstract
- Activation of astrocytes accompanies many brain pathologies. Reactive astrocytes have a beneficial role in acute neurotrauma but later on might inhibit regeneration. 2D-gel electrophoresis and mass spectrometry were applied to study the proteome difference in denervated hippocampus in wildtype mice and mice lacking intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin (GFAP-/-Vim-/-) that show attenuated reactive gliosis and enhanced posttraumatic regeneration. Proteomic data and immunohistochemical analyses showed upregulation of the adapter protein 14-3-3 four days postlesion and suggested that 14-3-3 upregulation after injury is triggered by reactive gliosis. Culture-derived isotope tags (CDIT) and mass spectrometry demonstrated that 14-3-3 epsilon was the major isoform upregulated in denervated hippocampus and that its upregulation was attenuated in GFAP-/-Vim-/- mice and thus most likely connected to reactive gliosis.
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| 19. |
- Uyama, N, et al.
(författare)
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Hepatic stellate cells express synemin, a protein bridging intermediate filaments to focal adhesions.
- 2006
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Ingår i: Gut. - : BMJ. - 0017-5749. ; 55:9, s. 1276-89
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: In the liver, stellate cells play several important (patho)physiological roles. They express a broad but variable spectrum of intermediate filament (IF) proteins. The aim of this study was to investigate the expression and functions of the intermediate filament protein synemin in hepatic stellate cells (HSCs). METHODS: In isolated and cultured rat HSCs, synemin expression was examined by quantitative reverse transcriptase polymerase chain reaction, western blotting, and immunocytochemistry. Protein-protein interaction between synemin and possible binding partners was investigated by co-immunoprecipitation and confocal microscopy. RESULTS: Expression of synemin was significantly downregulated with increased culture time. In 1-day cultured HSCs, synemin associated with other IF proteins (GFAP, desmin, and vimentin), and with the focal adhesion proteins vinculin and talin, but not with alpha-actinin or paxillin. Synemin IF and focal adhesion proteins co-localised in long slender processes, but not in the lamellipodia. In human and rat liver tissue, the presence of synemin was investigated by immunohistochemistry. In normal rat and human livers, synemin immunoreactivity was found in HSCs, smooth muscle cells of hepatic arterioles, and nerve bundles in portal tracts, but not in portal fibroblasts. In CCl4-intoxicated rat livers and in human cirrhotic livers, immunoreactivity for synemin in the parenchymal tissue was decreased. Thus synemin was expressed in quiescent HSCs but not in portal fibroblasts; and synemin expression decreased with HSC activation in vivo during chronic liver damage and with HSC activation in culture. CONCLUSIONS: Synemin forms heteropolymeric filaments with type-III IF proteins and acts as a bridging protein between IFs and a specific type of focal adhesions.
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| 20. |
- Verardo, Mark R, et al.
(författare)
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Abnormal reactivity of muller cells after retinal detachment in mice deficient in GFAP and vimentin.
- 2008
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Ingår i: Investigative ophthalmology & visual science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 49:8, s. 3659-65
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine the roles of glial fibrillary acidic protein (GFAP) and vimentin in M?ller cell reactivity. METHODS: Retinal detachments were created in mice deficient for GFAP and vimentin (GFAP(-/-)vim(-/-)) and age-matched wild-type (wt) mice. The reactivity of the retina was studied by immunofluorescence and electron microscopy. RESULTS: M?ller cell morphology was different and glutamine synthetase immunoreactivity was reduced in the undisturbed GFAP(-/-)vim(-/-) retinas. After retinal detachment, M?ller cells formed subretinal glial scars in the wt mice. In contrast, such scars were not observed in GFAP(-/-)vim(-/-) mice. M?ller cells, which normally elongate and thicken in response to detachment, appeared compressed, thin, and "spikey" in the GFAP(-/-)vim(-/-) mice. The end foot region of M?ller cells in the GFAP(-/-)vim(-/-) mice often sheared away from the rest of the retina during detachment, corroborating earlier results showing decreased resistance of this region in GFAP(-/-)vim(-/-) retinas to mechanical stress. In regions with end foot shearing, ganglion cells showed intense neurite sprouting, as revealed by anti-neurofilament labeling, a response rarely observed in wt mice. CONCLUSIONS: M?ller cells are subtly different in the GFAP(-/-)vim(-/-) mouse retina before detachment. The end foot region of these cells may be structurally reinforced by the presence of the intermediate filament cytoskeleton, and our data suggest a critical role for these proteins in M?ller cell reaction to retinal detachment and participation in subretinal gliosis.
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| 21. |
- Widestrand, Åsa, 1978, et al.
(författare)
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Increased neurogenesis and astrogenesis from neural progenitor cells grafted in the hippocampus of GFAP-/- Vim-/- mice.
- 2007
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Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 25:10, s. 2619-27
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Tidskriftsartikel (refereegranskat)abstract
- After neurotrauma, ischemia, or neurodegenerative disease, astrocytes upregulate their expression of the intermediate filament proteins glial fibrillary acidic protein (GFAP), vimentin (Vim), and nestin. This response, reactive gliosis, is attenuated in GFAP(-/-)Vim(-/-) mice, resulting in the promotion of synaptic regeneration after neurotrauma and improved integration of retinal grafts. Here we assessed whether GFAP(-/-)Vim(-/-) astrocytes affect the differentiation of neural progenitor cells. In coculture with GFAP(-/-)Vim(-/-) astrocytes, neural progenitor cells increased neurogenesis by 65% and astrogenesis by 124%. At 35 days after transplantation of neural progenitor cells into the hippocampus, adult GFAP(-/-)Vim(-/-) mice had more transplant-derived neurons and astrocytes than wild-type controls, as well as increased branching of neurite-like processes on transplanted cells. Wnt3 immunoreactivity was readily detected in hippocampal astrocytes in wild-type but not in GFAP(-/-)Vim(-/-) mice. These findings suggest that GFAP(-/-)Vim(-/-) astrocytes allow more neural progenitor cell-derived neurons and astrocytes to survive weeks after transplantation. Thus, reactive gliosis may adversely affect the integration of transplanted neural progenitor cells in the brain. Disclosure of potential conflicts of interest is found at the end of this article.
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| 22. |
- Wilhelmsson, Ulrika, 1970, et al.
(författare)
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Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury.
- 2006
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 103:46, s. 17513-8
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Tidskriftsartikel (refereegranskat)abstract
- Reactive astrocytes in neurotrauma, stroke, or neurodegeneration are thought to undergo cellular hypertrophy, based on their morphological appearance revealed by immunohistochemical detection of glial fibrillary acidic protein, vimentin, or nestin, all of them forming intermediate filaments, a part of the cytoskeleton. Here, we used a recently established dye-filling method to reveal the full three-dimensional shape of astrocytes assessing the morphology of reactive astrocytes in two neurotrauma models. Both in the denervated hippocampal region and the lesioned cerebral cortex, reactive astrocytes increased the thickness of their main cellular processes but did not extend to occupy a greater volume of tissue than nonreactive astrocytes. Despite this hypertrophy of glial fibrillary acidic protein-containing cellular processes, interdigitation between adjacent hippocampal astrocytes remained minimal. This work helps to redefine the century-old concept of hypertrophy of reactive astrocytes.
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