CORTICAL ASTROGLIAL CONDITIONED MEDIUM INDUCES IN-VITRO RADIAL-LIKE FORMS

Cerebral cortex and striatal cell dissociates obtained from rat fetuses (E 17) were subcultured and enriched in astroglial cells before being grown in regional (cerebral cortex, striatum) astroglial conditioned media (CM) or defined basal medium. Incidence of radial-like astroglia (vimentin + or glial fibrillary acid protein, GFAP+) and length of processes in cortical cell subcultures showed a greater increase when exposed to cerebral cortex CM than to striatal CM or basal medium. Stellate (GFAP+) forms prevailed in subcultures grown in basal medium while striatal cells exposed to CM of either origin remained undifferentiated. Additionally, cultures were treated with various concentrations of cAMP (0.25 and 0.5 mM) and calcitonin gene related peptide (CORP) (0.1, 0.5, and 1.0 mu M). Under these conditions CM-exposed cultures (with predominant ''radial-like'' forms) did not increase stellate glial numbers, while fetal calf serum (FCS)-exposed cultures (morphologically undifferentiated) underwent significant degrees of stellate transformation. When CM-exposed cultures were shifted to FCS supplemented basal medium for 24-48 hr and then to basal medium alone prior to treatment, cAMP and CORP were effective in transforming flat astroglia into stellate morphology. Results are indicative of the existence of astroglial diffusible factors affecting the in vitro expression of astroglial morphotypes from the cerebral cortex. Previous exposure to CM interferes with cytoskeletal astrocytic changes induced by cAMP and CGRP. It is speculated that astroglial factors could act in vivo to maintain the expression of radial-like cells during early developmental stages of the cerebral cortex, but it would not be effective in E 17 striatum. It is also suggested that transformation of radial glia into astrocytes may require previous dedifferentiation of the cytoskeleton. (C) 1995 Wiley-Liss, Inc.