IDENTIFICATION OF GLIAL-CELL TYPES INVOLVED IN MEDIATING EPIDERMAL GROWTH-FACTORS EFFECTS ON SEPTAL CHOLINERGIC NEURONS

We found previously that epidermal growth factor (EGF) decreases choli ne acetyltransferase (ChAT) activity in forebrain cholinergic neurons in vitro indirectly via glia (Kenigsberg et al.: Neuroscience 50: 85-9 7, 1992). However, which glial type(s) are implicated in this response remained to be determined. Here we report that in primary cultures fr om the fetal rat medial septal area the complete elimination of oligod endrocytes or partial elimination of microglia from these cultures doe s not change the cholinergic cell response to EGF. However, the elimin ation of astroglia in our cultures by alpha-aminoadipic acid treatment blocks EGF's effects on the cholinergic neurons. Co-culture experimen ts using pure neuronal and purified glial cells from the medial septum further demonstrate that the cholinergic cell response to EGF can be maintained in the presence of astroglia only. In addition, it appears that EGF regulates the release of soluble factors from pure astroglial cultures following their peak mitotic response to EGF that decreases ChAT enzymatic activity. This soluble cholinergic neuromodulatory acti vity found in conditioned media from EGF-treated astrocytes has a mole cular weight greater than or equal to 10 kD and loses potency followin g multiple freeze-thaw cycles. These results suggest that a direct gli al cell response to a specific glial growth factor like EGF may have a n important impact on the expression of local neurons, like the cholin ergic in the forebrain. (C) 1995 Wiley-Liss, Inc.