The influence of neuronal cells on the development of glutamine synthetase in astrocytes in vitro.

The influence of neurons on the development of astroglial cells was examined in vitro using glutamine synthetase (GS) activity as an index of metabolic maturation. The GS activity in forebrain astrocytes was significantly increased (about 70%) when they were co-cultured with forebrain neuronal cells. A similar effect was also observed when astrocytes from the immature septum, hippocampus or cerebellum were co-cultured with neurons derived from the septal-diagonal band region. The magnitude of the effect was not uniform; the cerebellar astrocytes, with relatively low GS activity, showed a greater (about 290%) quantitative response to the subcortical nerve cells than did the septal (about 115%) or the hippocampal (about 120%) astroglial cells. The addition of conditioned medium derived from neuronal cultures or plating the cells on a substratum of heat-killed nerve cells, elevated the GS activity of astroglial cells by 33% and 39%, respectively. Our results indicate that a trophic factor secreted by neurons and direct contact with the nerve cell matrix, are both involved in the regulation of the differentiation of astrocytes.