Morphological modulation of cultured rat brain astroglial cells: Antagonism by ganglioside GM 1

Abstract

Secondary cultures of neonatal rat astroglial cells, maintained in a serum-free, chemically defined medium were treated with several agents thought to activate cyclic AMP-synthesizing systems. Dibutyryl cyclic AMP (dBcAMP), forskolin and cholera toxin promoted, within 2 h, the near-complete conversion of 1-day-old (D1) astroglial cells from a flat, epitheliod morphology to a stellate (starshaped) morphology. With all 3 agents, cell susceptibility to morphological change declined with culture age, 5-day-old cultures failing to respond altogether. D1 cultures, after 48 h of treatment, had reverted to the flat morphology. Gangliosides reported to stimulate adenylate cyclase were also tested, using purified GM 1. GM 1 failed to stimulate the conversion to stellate morphologies. GM 1, however, did affect these astroglial cells by causing a block or reversal of their morphological response to dBcAMP, forskolin or cholera toxin. The GM 1 response was specific for the intact ganglioside molecule, asialo GM 1 and sialic acid having no effect. Gangliosides GD 1a, GD 1b and GT 1b were also active, being effective at ca. 4-fold lower concentrations. The response to GM 1 appeared to involve a direct interaction with the astroglial cell, rather than influencing either substratum or medium components.