Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment

Cornelia Franke, Michael Nöldner, Reham Abdel-Kader, Leslie N. Johnson-Anuna, W. Gibson Wood, Walter E. Müller, Gunter P. Eckert

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)438-445
Number of pages8
JournalNeurobiology of Disease
Volume25
Issue number2
DOIs
StatePublished - Feb 2007

Bibliographical note

Funding 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.

Keywords

  • Bax
  • Bcl-2
  • Guinea pigs
  • HA 14-1
  • Neuroprotection
  • SNP
  • Simvastatin

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