DEFICIENCY OF ESSENTIAL NEUROTROPHIC FACTORS IN CONDITIONED MEDIA PRODUCED BY ETHANOL-EXPOSED CORTICAL ASTROCYTES

Prior research in this laboratory has shown that in utero ethanol expo sure adversely affects the development of serotonergic neurons. The cu rrent study investigated the hypothesis that cortical astrocytes produ ce trophic factors which are essential for the development of the feta l precursors of serotonergic and other raphe neurons (e.g. rhombenceph alic neurons), and that ethanol exposure impairs the production of the se factors by astrocytes. The results of these experiments demonstrate d that cultured cortical astrocytes produce trophic factors which are necessary for the development of rhombencephalic neurons. Conditioned media obtained from control astrocytes promoted both general neuronal development (increased cell number, cell survival,DNA content, protein content, and neurite outgrowth) and serotonergic neuronal development (increased number of serotonin (5-HT) immunopositive cells and [H-3]5 -HT uptake). However, the conditioned media produced by ethanol-treate d astrocytes (ECM) lacked essential neurotrophic factors. Neuronal cul tures maintained in ECM had reduced DNA and neuronal survival, and alt ered neurite outgrowth. 5-HT immunopositive neurons and [H-3]5-HT upta ke were also decreased in ECM cultures. Thus, the damaging effects of in utero ethanol exposure on developing serotonergic neurons may be du e to impaired production of astroglial neurotrophic factors.