Specific alteration of the Bax/Bcl2 ratio and cytochrome c without execution of apoptosis in the hippocampus of aged baboons

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Abstract
Purpose: During ageing, there may be an age-associated loss of particular nerve cells in specific brain areas. Recent studies highlight the role of apoptosis in the normal ageing of the brain, heart, and skeletal muscle. Particular attention is paid to the role of cytochrome c release from mitochondria and alterations in the pro- and anti-apoptotic proteins, Bax and Bcl-2, respectively. The aim of this study was to investigate the potential occurrence of apoptosis in the hippocampus of aged baboons. Methods: we have used the baboon as a potential non-human primate model for age-related pathology which afflicts the human brain. The TUNEL staining method was used to characterise the apoptotic cell death. For immunocytochemistry, antibodies directed against activated caspase-3, cytochrome c, Bcl-2 and Bax proteins were used. Results: Our results show that in hippocampi of aged baboons the immunoreactivities of the antiapoptotic agent Bcl-2 was not prominently changed, of the proapoptotic agent Bax was upregulated, of the cytochrome c was redistributed, and that caspase-3 was not activated. The TUNEL-staining method revealed no apoptotic cell death in hippocampi of aged baboons. Conclusions: This demonstrates that a specific alteration of the Bax/Bcl2 ratio occurs in the ageing baboon hippocampus which may directly influence the release of cytochrome c even without commitment to apoptosis.

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