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 exposure adversely affects the development of serotonergic neurons. The current study investigated the hypothesis that cortical astrocytes produce trophic factors which are essential for the development of the fetal precursors of serotonergic and other raphe neurons (e.g. rhombencephalic neurons), and that ethanol exposure impairs the production of these factors by astrocytes. The results of these experiments demonstrated 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 [3H]5-HT uptake). However, the conditioned media produced by ethanol-treated astrocytes (ECM) lacked essential neurotrophic factors. Neuronal cultures maintained in ECM had reduced DNA and neuronal survival, and altered neurite outgrowth. 5-HT immunopositive neurons and [3H]5-HT uptake were also decreased in ECM cultures. Thus, the damaging effects of in utero ethanol exposure on developing serotonergic neurons may be due to impaired production of astroglial neurotrophic factors.