Differences between reactive astrocytes and cultured astrocytes treated with di-butyryl-cyclic AMP

The long-standing idea that astrogliosis acts as a barrier for regenerating axons could be tested if an in vitro model of reactive astrocytes were available. The morphology and intermediate filament content of cultured perinatal astrocytes treated with di-butyryl-cyclic-AMP are reminiscent of reactive astrocytes evoked by injury. Thus, they have been proposed as a reactive astrocyte in vitro model. However, we show here that di-butyryl-cyclic-AMP-treated astrocytes are much closer to untreated neonatal cells than to reactive astrocytes in vivo, when using other immunohistochemical markers of living reactive glia (i.e. EGF receptor or laminin). Furthermore, living di-butyryl-cyclic-AMP-treated astrocytes and untreated, flat, epithelioid cells, as well as their purified plasma membranes, had similar neurite outgrowth promoting properties, whereas membranes from gliotic tissue enriched in reactive astrocytes inhibited neurite outgrowth. Our observations indicate that di-butyryl-cyclic-AMP treatment leads, at best, to a morphological model of reactive cells that does not share many properties of reactive astrocytes in vivo.