Regulation of production by primary cultures of rat forebrain astrocytes of a trophic factor important for the development of cholinergic neurons.

The possibility was examined for the production of a trophic factor by astrocytes important for the biochemical development of cholinergic neurons. The activity of choline acetyltransferase (ChAT) was used as a marker to study the maturation of cholinergic neurons, while the metabolic state of astrocytes was monitored in terms of glutamine synthetase activity. When the dissociated cells, derived from the septal-diagonal band region of embryonic rat brain, were cultured either on a preformed layer of highly enriched astrocytes or in the presence of astrocyte-conditioned medium, a marked increase was observed in the expression of ChAT activity. Similar effect was not noticed when cerebellar granule cells replaced the astrocytes. The production of cholinergic factor was decreased when the astroglial cells were induced to proliferate by epidermal growth factor, whereas its production was increased when quiescent astrocytes were treated with a low dose of cytosine arabinoside. The results would indicate that a trophic factor important for the development of cholinergic cells is produced by astrocytes, and that exogenously added agents influencing astroglial metabolism have a marked regulatory effect on the production of this trophic factor.