Reactive astrocytes upregulate Fas (CD95) and Fas ligand (CD95L) expression but do not undergo programmed cell death during the course of anterogradedegeneration

Tissue homeostasis is determined by a balance between proliferation and apo ptosis. Various lesions in the brain are accompanied by proliferation and s ubsequent death of glial cells, but the mechanisms that limit this expansio n of glial populations remains unknown. One possible candidate is the death ligand, FasL, and its receptor Fas, because the expression of both protein s was reported on glial cells. To elucidate the expression and putative fun ction of Fas and FasL on proliferative glial cells, we performed stereotact ic lesion of the entorhinal cortex of adult rats. Such lesions induce proli feration of astrocytes and microglial cells in the hippocampal fields of an terograde degeneration. Subsequently, the total number of both cell types r eturns to pre-lesion counts. We found that Fas and FasL is strongly upregul ated on astrocytes in the zone of anterograde degeneration with a peak 5 da ys postlesion (dpl) and a return to control levels at 10 dpl. However, evid ence for astrocytic cell death was neither detected by TUNEL staining, immu nocytochemistry for c-Jun, and apoptosis-specific protein (ASP), nor by sta ining for morphologic hallmarks of apoptotic or necrotic cell death at the light and electron microscopic level. Thus, increased expression of Fas and FasL is not accompanied by cell death of reactive astrocytes during antero grade degeneration. GLIA 32:25-41, 2000. (C) 2000 Wiley-Liss, Inc.