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

Abstract

Tissue homeostasis is determined by a balance between proliferation and apoptosis. Various lesions in the brain are accompanied by proliferation and subsequent death of glial cells, but the mechanisms that limit this expansion of glial populations remains unknown. One possible candidate is the death ligand, FasL, and its receptor Fas, because the expression of both proteins was reported on glial cells. To elucidate the expression and putative function of Fas and FasL on proliferative glial cells, we performed stereotactic lesion of the entorhinal cortex of adult rats. Such lesions induce proliferation of astrocytes and microglial cells in the hippocampal fields of anterograde degeneration. Subsequently, the total number of both cell types returns to pre-lesion counts. We found that Fas and FasL is strongly upregulated on astrocytes in the zone of anterograde degeneration with a peak 5 days postlesion (dpl) and a return to control levels at 10 dpl. However, evidence for astrocytic cell death was neither detected by TUNEL staining, immunocytochemistry for c-Jun, and apoptosis-specific protein (ASP), nor by staining 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 anterograde degeneration.