The present study determined if chronic simvastatin administration in vivo would provide neuroprotection in brain cells isolated from guinea pigs after challenge with the Bcl-2 inhibitor HA 14-1 or the NO donor sodium nitroprusside (SNP). Bcl-2 levels were significantly increased in brains of simvastatin-treated guinea pigs while levels of the pro-apoptotic protein Bax were significantly reduced. The ratio of Bax/Bcl-2, being a critical factor of the apoptotic state of cells, was significantly reduced in simvastatin-treated animals. Cholesterol levels in the brain remained unchanged in the simvastatin group. Brain cells isolated from simvastatin-treated guinea pigs were significantly less vulnerable to mitochondrial dysfunction and caspase-activation. These results provide new insight into potential mechanisms for the protective actions of statins within the CNS where programmed cell death has been implicated.
Bibliographical noteFunding Information:
This work was supported by the Hannah-Bragard-Apfel-Foundation, Hirnliga and AFI grant No. 02806 and by grants from the National Institutes of Health AG-23524, AG-18357, NATO Collaborative Linkage Grant (980136) and resources/facilities of the Minneapolis VA Medical Center.
- Guinea pigs
- HA 14-1