ASTROCYTES PLAY A MAJOR ROLE IN THE CONTROL OF NEURONAL PROLIFERATIONIN-VITRO

The elements that control neuronal proliferation are largely unknown. Proliferating neurons in cultures of goldfish brain were studied in an attempt to identify the cell types involved. Neuronal proliferation w as found to occur only when the neuronal stem cells were in direct con tact with astrocytes, and never directly on the substrate. The regulat ion of neuronal proliferation thus appears to be mediated, at least in part, by contact with astrocytes. In addition, neurite extension was inhibited by medium conditioned by fish astrocytes. Since neurite exte nsion and neuronal proliferation are mutually exclusive processes, inh ibition of neurite extension by soluble substances derived from the as trocytes is probably one of the mechanisms controlling neuronal prolif eration. The complex reciprocal relationship between neurons and astro cytes is also demonstrated by an observed inhibition of astrocytic pro liferation by medium conditioned by differentiating fish neurons. This inhibition of astrocytic proliferation might be part of a mechanism t hrough which interference with neuronal differentiation by astrocytes is avoided. The results of this study thus suggest that astrocytes, in addition to their known roles in controlling neuronal migration, neur onal differentiation and neurite elongation, may also play a role in t he control of neuronal proliferation.