Contribution of heparan sulfate to the non-permissive role of the midline glia to the growth of midbrain neurites

Radial glial cells and astrocytes are heterogeneous with respect to morphol ogy, cytoskeletal- and membrane-associated molecules and intercellular inte ractions. Astrocytes derived from lateral (L) and medial (M) midbrain secto rs differ in their abilities to support neuritic growth of midbrain neurons in coculture (Garcia-Abreu et al. J Neurosci Res 40:471, 1995). There is a correlation between these abilities and the differential patterns of lamin in (LN) organization that is fibrillar in growth-permissive L astrocytes an d punctate in the non-permissive M astroglia (Garcia-Abreu et al. Neuro-Rep ort 6:761, 1995). There are also differences in the production of glycosami noglycans (GAGs) by L and M midbrain astrocytes (Garcia-Abreu et al. Glia 1 7:339, 1996). We show that the relative amounts of the glycoproteins lamini n LN, fibronectin (FN) and tenascin (TN) are virtually identical in L and M glia, thus, confirming that an abundant content of LN is not sufficient to promote neurite growth. To further analyze the role of GAGs in the propert ies of M and L glia, we employed enzymatic degradation of the GAGs chondroi tin sulfate (CS) and heparan sulfate (HS). Treatment with chondroitinase ha s little effect on the non-permissive properties of M glia but reduces the growth-supporting ability of L glia. By contrast, heparitinase I produces n o significant changes on L glia but leads to neurite growth promotion by M glia. Taken together, these results suggest that glial CS helps to promote neurite growth and, more importantly, they indicate that a HS proteoglycan is, at least, partially responsible for the non-permissive role of the midl ine glia to the growth of midbrain neurites. (C) 2000 Wiley-Liss, Inc.