BAX EXPRESSION IN MAMMALIAN NEURONS UNDERGOING APOPTOSIS, AND IN ALZHEIMERS-DISEASE HIPPOCAMPUS

Recent studies indicate that the proto-oncogene Fax, and other related proteins (eg Bcl-2) may play a major role in determining whether cell s will undergo apoptosis under conditions which promote cell death. In creased expression of Bar has been found to promote apoptosis, while o ver-expression of Bcl-2 can inhibit apoptosis. To investigate the role of Bar in nerve cell death in the rat brain we examined the level of Bar expression in cells undergoing apoptosis, using a hypoxic-ischemic stroke model. We found that Bar was expressed at high levels in the n uclei of neurons in the hippocampus, cortex, cerebellum, and striatum on the control side, and that Bar levels increased in hippocampal neur ons undergoing apoptosis on the stroke side, and then declined (correl ating with cell loss). In the Alzheimer's disease hippocampi we found a concentrated localisation of Fax in senile plaques, which correlated with the localisation of beta-amyloid protein in adjacent sections fr om the same brains. beta-Amyloid positive plaques are thought to contr ibute to the Alzheimer's disease process, possibly via an apoptotic me chanism, and this may occur via an increase in Bar in these areas. Bar was also strongly stained in tau-positive tangles in Alzheimer's dise ase hippocampi, suggesting Fax may play a role in tangle formation. In addition, we observed a loss of Bar expression in the dentate granule cells of Alzheimer's disease hippocampi compared with moderate Bar ex pression in control hippocampi, and this loss may be related to the su rvival of these neurons in Alzheimer's disease. Finally, we observed s ubstantially different staining patterns of Bar using three different commercially available antisera to Fax, indicating the need for cautio n when interpreting results in this area.