NEUROSTEROIDS MODULATE THE REACTION OF ASTROGLIA TO HIGH EXTRACELLULAR POTASSIUM LEVELS

The extracellular concentration of potassium ([K+](0)) in brain tissue is modified by neuronal activity and is increased under several patho logical conditions. The influence of neurosteroids on the astroglia re sponse to high [K+](0) was assessed on cultured slices from rat hippoc ampus. Exposure to [K+](0) above physiological (3 mM) levels resulted in the progressive appearance of cell processes immunoreactive for gli al fibrillary acidic protein (GFAP). The maximal effect was observed a t 50 mM [K+](0), and further increases of [K+](0) did not increase the extension of GFAP-immunoreactive processes. The effect was observed a s early as 10 min after increasing [K+](0), was independent of new pro tein synthesis, and was reversible, reaching control conditions by 15 h after resetting [K+](0) to physiological levels. Gonadal hormones an d neurosteroids had prominent and variable effects on the stimulatory influence of high [K+](0) on astroglia morphology. At physiological [K +](0), 17 beta-estradiol and pregnenolone, as well as its sulfate deri vative, increased the extension of GFAP-immunoreactive processes. Howe ver, at high [K+](0), testosterone, pregnenolone, and dehydroepiandros terone and its sulfate derivative decreased the extension of GFAP-immu noreactive processes. Effects of gonadal hormones and neurosteroids we re blocked by the protein synthesis inhibitor cycloheximide. These res ults suggest that non-genomic effects of high [K+](0) on glial cells i nteract with genomic effects of steroids to modulate astroglia morphol ogy. (C) 1996 Wiley-Liss, Inc.