Article

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.

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    • "It was demonstrated that its expression was limited to specific astrocyte cell lines or subpopulations during CNS development [66] [67]. Paradoxically, TN-C was considered both as a repulsive substrate for neuronal and astrocytic growth [68] [69] and as a permissive one, by providing axonal guidance cues [66] [67] [70] [71]. Depending on the context, such as the expression of other ECM molecules, TN-C can have the opposite differential effects on neuronal growth. "
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    • "Tenascin-C has been shown to be expressed and secreted by numerous populations of astrocytes (Mahler, et al., 1996; Meiners, et al., 1995). Although astrocytes have been shown to exert negative affects on neurons in vitro and in grafting paradigms, these studies utilized astrocytes in latter developmental stages (Krobert, et al., 1997; Meiners, et al., 1995). Also, it is likely that the mechanical dissociation involved in the present investigation resulted in isomorphic astrogliosis (Liberto, et al., 2004). "
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    • "After incubation for two weeks, fibrous astrocytes and protoplasmic astrocytes, which became tile-shaped with cell contact were observed. A similar finding has been reported by Meiners et al. (1995), who examined cultures of astrocytes from the cerebral cortices of newborn Sprague-Dawley rats and found that fibrous astrocytes assume "rocky" shapes and express TN at extremely high levels. As fibrous astrocytes did not appear in the primary cultures of astrocytes from the TN-deficient mice it appears that tenascin is required for the development of fibrous astrocytes. "
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