Glial fibrillary acidic protein is necessary for mature astrocytes to react to beta-amyloid

Upregulation of the glial fibrillary acidic protein (GFAP) in astrocytes is a hallmark of the phenomenon known as reactive gliosis and, yet, the funct ion of GFAP in this process is largely unknown. Our previous studies have s hown that mature astrocytes react vigorously to substrate bound beta-amyloi d protein (BAP) in a variety of ways (i.e., increased GFAP, enhanced motili ty, unusual aggregation patterns, inhibitory ECM production). In order to u ncover which, if any, of these phenomena are causally related to the functi on of GFAP, primary cortical astrocytes from transgenic mice lacking GFAP w ere cultured on BAP substrates at low or high density and at various length s of time following in vitro maturation. Differences between mutant and con trol cells became progressively more obvious when cells were matured in vit ro for two weeks or longer and especially in cultures that were at high den sity. Mature control astrocytes show a dramatic response to BAP by aggregat ing into a meshwork of rope-like structures that completely bridge over the peptide surface. In marked contrast, mature GFAP-null astrocytes initiate the response much more slowly and had a much reduced ability to aggregate t ightly. Furthermore, we prepared hippocampal slice cultures from GFAP-/- an d GFAP+/+ mice and compared their astrocytic responses to injected BAP. GFA P-/- astrocytes of hippocampal slice cultures failed to form a barrier-like structure around the edge of the BAP deposit as did GFAP+/+ astrocytes. Ou r data suggest that GFAP may be essential for mature astrocytes to constrai n certain types of highly inflammatory lesions in the brain. (C) 1999 Wiley -Liss, Inc.