Intermediate filaments regulate astrocyte motility

Lepekhin, Eugene A.; Eliasson, Camilla; Berthold, Claes‐Henric; Berezin, Vladimir; Bock, Elisabeth; Pekny, Milos

doi:10.1046/j.1471-4159.2001.00595.x

Cited by 148 publications

(119 citation statements)

References 32 publications

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Section: Eph/ephrinsmentioning

confidence: 99%

“…After SCi, both vimentin and GFAP are up-regulated in reactive astrocytes [60] . An analysis of mice that are genetically deficient in vimentin or GFAP showed that glial scar , most likely due to the impaired astrocytic motility resulting from the ablation of intermediate filaments [62] .Moreover, the genetic absence of vimentin and GFAP also improves axonal sprouting [63] and facilitates functional recovery in the context of a spinal cord hemisection model [64] .Transforming growth factor-beta TGF-beta expression increases immediately after SCi in the injured segment [65] .Both TGF-beta1 and TGF-beta2 are detectable in macrophages and astrocytes, while TGF-beta1 is also neuron-associated [66] . The cellular localization and temporal expression pattern of TGF-beta after SCi suggest that early induction of TGF-beta1 at the point of SCi modulates acute inflammatory responses and glial scar formation [67] , while the later induction of TGF-beta2 indicates a regulatory role in the maintenance of the scar [68] .…”

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The glial scar in spinal cord injury and repair

2013

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Glial scarring following severe tissue damage and inflammation after spinal cord injury (SCi) is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarring process includes the misalignment of activated astrocytes and the deposition of inhibitory chondroitin sulfate proteoglycans. Here, we first discuss recent developments in the molecular and cellular features of glial scar formation, with special focus on the potential cellular origin of scar-forming cells and the molecular mechanisms underlying glial scar formation after SCi. Second, we discuss the role of glial scar formation in the regulation of axonal regeneration and the cascades of neuro-inflammation. Last, we summarize the physical and pharmacological approaches targeting the modulation of glial scarring to better understand the role of glial scar formation in the repair of SCi.Keywords: glial scar; spinal cord injury; axonal regeneration; astrocyte activation; reactive astrogliosis; neuroinflammation IntroductionSpinal cord injury (SCi) is a common and devastating central nervous system (CNS) insult that results in disruption of cord microstructure and is followed by limited neuronal regeneration and insufficient functional recovery in adult mammals. After severe SCi, and in response to changes in the local microenvironment, astrocytes, the most abundant glial cells in the CNS, transform into reactive astrocytes and undergo dramatic morphological changes [1] as well as massive variations in gene expression [2] . Reactive astrocytes, the major component of glial scars, along with other cells in the spinal cord and blood-borne cells leaking from the damaged blood-spinal cord barrier, participate in the process of scar formation [3] .From the historical perspective, a glial scar is recognized as an impediment to the regeneration of axons in the cord because of the irregular rearrangement of hypertrophic astrocytic processes, as well as major components of the axonal inhibitory extracellular matrix (ECM), including chondroitin sulfate proteoglycans (CSPGs) that are secreted by the reactive astrocytes [4] . Currently, increasing evidence is advancing our knowledge of the mechanism of the formation of glial scars after a lesion and the roles of glial scars in the regulation of neuro-inflammation and repair processes [5,6] .This article reviews the following: (1) the molecular and cellular properties of glial scar formation following SCi;(2) the roles of glial scar formation in axonal regeneration and neuro-inflammation; and (3) the current status of scarmodulating therapeutic strategies for spinal cord repair after injury. Molecular and Cellular Properties of Glial Scars Characterization of Glial ScarsTraumatic damage of the spinal cord can result in seallike scar tissue in the lesion zone, which is filled with dense cellular components and a connective matrix. Generally, the scar tissue is classified into two parts, fibrotic and glial. 422The fibrotic scar, primarily composed of invading fibrobl...

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Section: Eph/ephrinsmentioning

confidence: 99%

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confidence: 99%

The glial scar in spinal cord injury and repair

2013

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“…GFAP is the only IF protein that may form filaments on its own (Eliasson et al, 1999). The lack of expression of either GFAP or vimentin inhibits the mean cell speed of astrocytes, whereas the persistence in direction remains unchanged (Lepekhin et al, 2001). Removal of both of these proteins, leading to a complete absence of IFs in astrocytes, decreases the mean cell speed further, without any effect on persistence time (Lepekhin et al, 2001).…”

Section: Maumenee Personal Communication)mentioning

confidence: 99%

“…The lack of expression of either GFAP or vimentin inhibits the mean cell speed of astrocytes, whereas the persistence in direction remains unchanged (Lepekhin et al, 2001). Removal of both of these proteins, leading to a complete absence of IFs in astrocytes, decreases the mean cell speed further, without any effect on persistence time (Lepekhin et al, 2001). These studies indicate that IFs are an integral part of the cell motility machinery in astrocytes.…”

Section: Maumenee Personal Communication)mentioning

confidence: 99%

βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

Sinha

Klise

Sergeev

et al. 2008

Molecular and Cellular Neuroscience

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Vascular remodeling is a complex process critical to development of the mature vascular system. Astrocytes are known to be indispensable for initial formation of the retinal vasculature; our studies with the Nuc1 rat provide novel evidence that these cells are also essential in the retinal vascular remodeling process. Nuc1 is a spontaneous mutation in the Sprague-Dawley rat originally characterized by nuclear cataracts in the heterozygote and microphthalmia in the homozygote. We report here that the Nuc1 allele results from mutation of the βA3/A1-crystallin gene, which in the neural retina is expressed only in astrocytes. We demonstrate striking structural abnormalities in Nuc1 astrocytes with profound effects on the organization of intermediate filaments. While vessels form in the Nuc1 retina, the subsequent remodeling process required to provide a mature vascular network is deficient. Our data implicate βA3/A1-crystallin as an important regulatory factor mediating vascular patterning and remodeling in the retina.

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“…The up-regulation of torsinA in reactive astrocytes might facilitate one or more protective functions of astrocytes such as glutamate uptake via movement of the polytopic glutamate transporter to the cell surface. Alternatively, torsinA might contribute to the morphological and topological changes that reactive astrocytes must undergo in order to facilitate synaptogenesis and network reorganization (Lepekhin et al, 2001;Witcher et al, 2007).…”

Section: Post-ischemic Torsina Expression In the Cnsmentioning

confidence: 99%

TorsinA and the Pathophysiology of DYT1 Dystonia

Zhao¹

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Intermediate filaments regulate astrocyte motility

Cited by 148 publications

References 32 publications

The glial scar in spinal cord injury and repair

The glial scar in spinal cord injury and repair

βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

TorsinA and the Pathophysiology of DYT1 Dystonia

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