摘要:

AbstractAxons of the mammalian central nervous system do not regenerate spontaneously after axonal injury, unlike the central nervous system axons of fish and amphibians and the peripheral nervous system of mammals, which possess a good regenerative ability (Grafstein:The Retina: A Model for Cell Biology Studies, Part II, 1986; Kiernan: Biol Rev 54:155–197, 1979; Murray: J Comp Neurol 168:175–196, 1976; Ramony Cajal:Degeneration and Regeneration of the Nervous System, 1928; Reier and Webster: J Neurocytol 3:591–618, 1974; Sperry:Physiol Zool23:351–361, 1948). It was previously believed that intrinsic differences between the central nervous system neurons of mammals and fish account for their differences in regenerative ability. The past decade, however, has seen an accumulation of evidence, indicating that mammalian central nervous system neurons are able to regenerate injured axons, at least to some extent. This was first demonstrated by Aguayo and colleagues (David and Aguayo: Science 214:931–933, 1981; Kierstead et al: Science 246:255–257, 1989), who showed that injured mammalian central nervous system axons can grow for a considerable distance into an autograft of a peripheral nerve. It was also demonstrated that injured rabbit optic axons can regenerate into their own environment (i.e., into the distal part of the injured optic nerve), if the injured nerve is treated so as to make it conducive for growth (Lavie et al: J Comp Neurol 298:293–314, 1990; Eitan et al: Science 264:1764–1768, 1994). It is generally believed today that the glial cells surrounding the axons play a crucial role in determining the regenerative capacity of any central nervous system. In this review, we discuss various aspects of glial cells in the context of regeneration, with special emphasis on similarities and differences between the glial cells of rat and fish optic nerves, representing a nonregenerative and a regenerative system, respectively. © 1995

ISSN:0894-1491    

DOI:10.1002/glia.440130302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractAstrocytes have been shown to express voltage‐sensitive Na+channels, but the molecular structure of these channels is not yet known. Recent studies have demonstrated the expression of rat brain voltage‐sensitive Na+channel mRNAs in astrocytes. In this study, we used a combined non‐radioactive in situ hybridization immunocytochemistry method to investigate the expression of voltage‐sensitive Na+channel ß1 subunit (Naß1) mRNA in definitively identified, GFAP‐positive astrocytes cultured from two different regions of the rat brain, cerebrum and cerebellum. In general, two morphologically distinct types of GFAP‐positive astrocytes were observed in culture: flat, fibroblast‐like and stellate, process‐bearing. We observed a differential expression ofNaß1 mRNA in GFAP‐positive astrocytes: (1) stellate astrocytes expressed Naß1 mRNA, although the level of Naß1 mRNA expression was variable, and (2) flat astrocytes generally did not express Naß1 mRNA. Moreover, Bergmann‐like cells from cerebellum did not express Naß mRNA, while the granule cells associated with Bergmann‐like cell expressed Naß mRNA. These observations indicate that Naß mRNA is differentially expressed in rat astrocytes with various morphologies in

ISSN:0894-1491    

DOI:10.1002/glia.440130303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractAn increase in the expression of the glial fibrillary acidic protein (GFAP) gene by astrocytes appears to constitute a crucial component of the brain's response to injury because it is seen in many different species and features prominently in diverse neurological diseases. Previously, we have used a modified GFAP gene (C‐339) to target the expression of β‐galactosidase (β‐gal) to astrocytes in transgenic mice (Mucke et al.; New Biol 3:465–474 1991). To determine to what extent the in vivoThroughout this text, “in vitro” refers to cells grown in culture in culture and “in vivo” to living animals.expression of GFAP‐driven fusion genes is influenced by intragenic GFAP sequences, the E. coli lacZ reporter gene was either placed downstream of approximately 2 kb ofmurine GFAP 5′ flanking region (C‐259) or ligated into exon 1 of the entire murine GFAP gene (C‐445). Transgenic mice expressing C‐259 versus C‐445 showed similar levels and distributions of β‐gal activity in their brains. Exclusion of intragenic GFAP sequences from the GFAP‐lacZ fusion gene did not diminish injury‐induced upmodulation ofastroglial β‐gal expression or increase β‐gal expression in non‐astrocytic brain cells. These results demonstrate that 2 kb ofmurine GFAP 5′ flanking region is sufficient to restrict transgene expression primarily to astrocytes and to mediate injury‐responsiveness in vivo. This sequence therefore constitutes a critical target for mediators of reactive astrocytosis. While acute penetrating brain injuries induced focal increases in β‐gal expression around the lesion sites in C‐259, C‐445, and C‐339 transgenic mice, infection of C‐339 transgenic mice with scrapie led to a widespread upmodulation of astroglial β‐gal expression. Hence, GFAP‐lacZ transgenic mice can be used to monitor differential patterns of astroglial activation in vivo. These and related models should facilitate the assessment of strategies aimed at the in vivo manipulation of G

ISSN:0894-1491    

DOI:10.1002/glia.440130304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractPrevious reports have shown that tumor necrosis factor (TNF) exerts a role on the physiology of astrocytes under inflammatory situations. The signalling for biological effects of this and other cytokines are usually exerted through cell surface receptors. In this study, we have demonstrated the presence of a surface TNF α receptor type I in murine astrocytes of both SJL/J and BALB/c origin, using125I‐labelled recombi‐nant mouse TNFα. A linear Scatchard plot indicates the presence of only one type of receptor with a MW of 58 kDa (Type I TNF receptor) that binds the ligand with a Kd of 1 10−9M. There are 3,000 copies of this receptor on untreated astrocytes. The results also indicate that receptor‐bound TNF is rapidly internalized at 37°C and degraded intracellularly to a principal molecular species which elutes from HPLC reverse‐phase columns at 38% acetonitrile rather than at 60% as native TNFα does. The binding is up‐regulated by increasing the number of receptors (but not its affinity) by treatments with Theiler's murine encephalomyelitis virus (TMEV), Con A and inflammatory cyto‐kines such as IL‐1, IL‐6 and INF‐β. It is not influnced by vaccinia virus, IL‐2, or LPS. This receptor may contribute to the initiation of perpetuation of the immune response which mediates the demyelinating inflammation induced by Theiler's vir

ISSN:0894-1491    

DOI:10.1002/glia.440130305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractMüller (glial) cells of the neonatal rabbit retina were cultured as confluent monolayers and exposed to enhanced concentrations of ammonia (0.25, 0.5, 1, 3, 7, and IC mM) in medium for various periods (30 min to 10 d). This caused, in a time‐ and dose‐dependent manner, similar changes in the Müller cells as had previously been described in cultured astrocytes. The most conspicuous events were (1) an increasing size of cell nuclei, (2) an accumulation of phagocytotic vacuoles, and (3) a rearrangement of intermediate filaments. (4) A considerable number of cells died when higher ammonia concentrations were applied for more than 1 h. Simultaneous application of dibutyrylcyclic adenosine monophosphate (dBcAMP) prevented almost completely both the increase in cell nucleus size and the changes of intermediate filaments, but only partly the early cell death of a subpopulation of cells, and the accumulation of phagocytotic vacuoles. Further changes evoked by enhanced ammonia concentration were (5) an accumulation of lipofuscin‐like material (“fatty degeneration”) revealed by lipophilic stain, (6) reduced immunoreactivity for cathepsin D, and increased immunoreactivity for (7) glial fibrillary acidic protein, (8) glutamine synthetase, and (9) bcl‐2 protooncogene protein. These findings are discussed in respect to the possible underlying pathophysiological mechanisms. © 1995 W

ISSN:0894-1491    

DOI:10.1002/glia.440130306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractGonadal steroids are known to affect astroglial morphology in developing and adult animals. Earlier studies of mixed neuronal‐glial cultures from fetal rat hypothalamus showed that glial fibrillary acidic protein (GFAP)‐immunoreactive cells with a polygonal shape were transformed into process‐bearing cells upon exposure to the ovarian hormone estradiol. This effect was dependent on a direct contact of astroglia with living hypothalamic neurons. The present study shows that somata and processes of neurons in such cultures were immunoreactive for polysialic acid (PSA); astroglia were immunonegative. PSA appears to participate in the estradiol‐induced shape changes since treatment with endoneuraminidase, an enzyme that specifically removes PSA from the cell surface, abolished PSA immunostaining and prevented the 17ß‐estradiol‐induced morphological changes of astroglia. In contrast, treatment with endoneuraminidase did not affect astroglial shape changes induced by basic fibroblast growth factor (bFGF), nor those induced by the addition of neurons to glial cultures. These results suggest that PSA on neuronal membranes, probably linked to the highly sialylated isoform of the neural cell adhesion molecule, is necessary for the expression of certain hormonally‐regulated neuro‐glial interactions. © 199

ISSN:0894-1491    

DOI:10.1002/glia.440130307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractExposure of the adult rat brain parenchyma to zinc induces an increase in the intracerebral expression of the metal‐binding protein, metallothionein, which is normally confined to astrocytes, ependymal cells, choroid plexus epithelial cells, and brain endothelial cells. Metallothionein is expressed only in diminutive amounts in astrocytes of the neonatal rat brain, which could imply that neonatal rats are devoid of the capacity to detoxify free metals released from a brain wound. In order to examine the influence of a brain injury on the expression of metallothionein in the neonatal brain, PO rats were subjected to a localized freeze lesion of the neocortex of the right temporal cortex. This lesion results in a disrupted blood‐brain interface, leading to extravasation of plasma proteins. From 16 h, reactive astrocytosis, defined as an increase in the number and size of cells expressing GFAP and vimentin, was observed surrounding the neocortical lesion site. Astrocytes and pial cells situated adjacent to the area of injury also became positively stained for metallothionein. At 3–6 days post‐lesion, the highest level of reactive astrocytes expressing metallothionein was observed. Neo‐Timm staining revealed that histochemically reactive zinc had disappeared from the lesion site. Extracellular albumin and metallolhionein‐positive astrocytes were absent approximately 2 weeks after the lesion, whereas reactive astrocytosis was still observed. These results show that a lesion of the neonatal rat brain induces a transient expression of metallothionein in reactive astrocytes, probably as a response to metals released from the site of the brain injury. © 1995 Wil

ISSN:0894-1491    

DOI:10.1002/glia.440130308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractN‐methyl‐D‐aspartate (NMDA)‐activated glutamate receptor subunits are invariably expressed in neurons, although NMDA‐activated currents have been recently described in Bergmann glia. To date, the NMDA receptor subunit 2B (NMDAR2B) was thought not to be expressed in adult cerebellum. In the present study we provide evidence, from in situ hybridization histochemistry, that Bergmann glial cells in rat brain express mRNA encoding the NMDAR2B subunit, most probably co‐expressed with the ubiquitous NMDAR1 subunit, while transcripts for other NMDAR2 subunits (A,C,D) were either not resolved or detected. Our findings suggest that Bergmann glial cells contain the molecular machinary to synthesize the NMDA receptor 2B subunit. The role of physiological NMDA receptors in the interaction between Bergmann glia and Purkinje neurons is not yet known. © 1995 Wil

ISSN:0894-1491    

DOI:10.1002/glia.440130309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:0894-1491    

DOI:10.1002/glia.440130301

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY