A distinct subset of tenascin/CS-6-PG-rich astrocytes restricts neuronal growth in vitro.

Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 01/1996; 15(12):8096-108.
Source: PubMed

ABSTRACT Astrocytes provide an optimal surface for attachment, migration, and growth of CNS neurons. Nonetheless, not all astrocytes are alike: our previous work demonstrated a heterogeneity in the ability of cultured astrocyte monolayers to support neuronal growth. Areas displaying a fibrous, uneven surface ("rocky" astrocytes) were shown to be restrictive substrates, whereas surrounding, flat areas were permissive substrates. However, whether these cell types are in fact different cannot be addressed using mixed cultures. Therefore, in the current study we used morphological criteria to isolate the two subpopulations from mixed astrocyte cultures established from the cerebral cortex of neonatal rats. Following isolation, the purified populations only produced progeny with the same phenotype as the parent cells. We then measured production of several extracellular matrix molecules putatively involved in neuronal guidance during development and quantitatively assessed neuronal behavior on the purified populations. Immunocytochemistry and immunoblotting showed that rocky astrocytes were enriched in tenascin and chondroitin-6- sulfate-containing proteoglycans, but not in laminin or fibronectin. In addition, these astrocytes, as well as their isolated matrix, were a less permissive substrate for neuronal growth than flat astrocytes/matrix. Neurite outgrowth was significantly increased on rocky astrocytes following treatment with chondroitinase ABC or AC, but not heparitinase or hyaluronidase. These data support a critical role for matrix-bound chondroitin-6-sulfate-containing proteoglycans. We hypothesize that rocky astrocytes represent a subtype of cells which form barriers to neuronal growth during cortical development.


Available from: Elizabeth M Powell, Apr 23, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Leptomeningeal cells migrate into the lesion cavity after stab wounds to the adult mammalian central nervous system (CNS) and interact with astrocytes that form a new glia limitans. However, it is not known if leptomeningeal cells alter the ability of astrocytes near the lesion to support axon growth. In this study, we have used an in vitro approach to assess leptomeningeal cell-astrocyte interactions in a model that resembles the interactions of these cells in vivo. We cultured rat cortical astrocytes on top of monolayers of leptomeningeal cells or astrocytes. Differences in the morphology, neurite growth promoting properties, and expression of various extracellular matrix molecules and β1-integrin were assessed. Astrocytes acquired a long slender morphology when plated on leptomeningeal cells. Functionally, astrocytes cultured on top of leptomeningeal monolayers supported less neurite growth. Similar results were also obtained when astrocyte monolayers were treated with leptomeningeal cell-conditioned medium. Quantitative immunofluorescence labeling showed a reduction in cell surface bound laminin on astrocytes plated on leptomeningeal monolayers. Qualitative assessment of the immunofluorescence labeling showed an increase in matrix-like deposits of tenascin-C and chondroitin sulfate proteoglycan under similar culture conditions. This study provides the first direct evidence that leptomeningeal cells reduce the neurite growth promoting properties of astrocytes. These results suggest that interactions with leptomeningeal cells may 1) induce the formation of the slender astrocyte processes that form parallel to the lesion wall after penetrating injuries to the CNS; and 2) contribute along with other factors to alter astrocytes near the site of injury to a state that is less permissive for axon growth and regeneration. GLIA 19:47–57, 1997. © 1997 Wiley-Liss, Inc.
    Glia 01/1997; 19(1). DOI:10.1002/(SICI)1098-1136(199701)19:1<47::AID-GLIA5>3.0.CO;2-7 · 5.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim: Pendulous monkshood root is traditionally used for the treatment of several inflammatory pathologies such as rheumatisms, wounds, pain and tumors in China. In this study, the anti-inflammatory and anticancer activities and the mechanism of crude ethanol extract of pendulous monkshood root (EPMR) were evaluated and investigated in vitro. Materials and Methods: The cytotoxic effects of EPMR on different tumor cell lines were determined by the MTT method. Cell apoptosis and cell nucleus morphology were assessed by Hoechst 33258 staining. Moreover, nitric oxide (NO) levels and intracellular oxidative stress in peritoneal macrophages were determined to further elucidate mechanisms of action. Results: The data showed that EPMR could produce significant dose-dependent toxicity on three kinds of tumor cells. Furthermore, EPMR displayed obvious anti- inflammatory effects on LPS-induced mouse peritoneal macrophages at the dosage of 4 - 200 μg/mL. The results demonstrated the therapeutic potential of Pendulous Monkshood Root on cancer and inflammatory diseases. Conclusion: Our results indicate that EPMR has anti-inflammatory and anticancer properties, suggesting that pendulous monkshood root may be a useful anti-tumor and anti-inflammatory reagent in the clinic.
    Asian Pacific journal of cancer prevention: APJCP 06/2013; 14(6):3569-73. DOI:10.7314/APJCP.2013.14.6.3569 · 1.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Matricellular proteins are secreted, nonstructural proteins that regulate the extracellular matrix (ECM) and interactions between cells through modulation of growth factor signaling, cell adhesion, migration, and proliferation. Despite being well described in the context of nonneuronal tissues, recent studies have revealed that these molecules may also play instrumental roles in central nervous system (CNS) development and diseases. In this minireview, we discuss the matricellular protein families SPARC (secreted protein acidic and rich in cysteine), Hevin/SC1 (SPARC-like 1), TN-C (Tenascin C), TSP (Thrombospondin), and CCN (CYR61/CTGF/NOV), which are secreted by astrocytes during development. These proteins exhibit a reduced expression in adult CNS but are upregulated in reactive astrocytes following injury or disease, where they are well placed to modulate the repair processes such as tissue remodeling, axon regeneration, glial scar formation, angiogenesis, and rewiring of neural circuitry. Conversely, their reexpression in reactive astrocytes may also lead to detrimental effects and promote the progression of neurodegenerative diseases.
    Neural Plasticity 01/2014; 2014:321209. DOI:10.1155/2014/321209 · 3.60 Impact Factor