Reduction but not cleavage of poly(ADP-ribose) polymerase during stress-mediated cell death in the rat hippocampus.

ABSTRACT

Sustained stress induces neuronal atrophy and death, especially in the hippocampus, which impairs hippocampal function. However, underlying mechanisms of stress-induced neuronal damage have not been precisely defined. We analyzed the molecular events related to apoptosis in the hippocampus of rats exposed to immobilization stress. Terminal dUTP nick end-labeling exhibited positive nuclei in the hippocampus of stressed rats, indicating DNA fragmentation. RT-PCR and Western blot analyses showed that immobilization stress increased and decreased the expression of pro-apoptotic gene bax and anti-apoptotic bcl-2 genes, respectively. Western blot analysis demonstrated that the characteristic 85 kDa apoptotic fragment of poly(ADP-ribose) polymerase (PARP) was not observed in the hippocampus subjected to immobilization stress. The amount of PARP protein was significantly reduced following stress. This study may provide a novel insight into molecular mechanisms implicated in hippocampal damage associated with stress.