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

Neurobiology of Disease (Feb 2007)

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

Affiliations

Cornelia Franke: Department of Pharmacology, ZAFES, Biocenter Niederursel, N260 Max-von-Laue Str. 9, University of Frankfurt, Germany
Michael Nöldner: Dr. Willmar Schwabe Group, Karlsruhe, Germany
Reham Abdel-Kader: Department of Pharmacology, ZAFES, Biocenter Niederursel, N260 Max-von-Laue Str. 9, University of Frankfurt, Germany
Leslie N. Johnson-Anuna: Department of Pharmacology, University of Minnesota, School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, MN, USA
W. Gibson Wood: Department of Pharmacology, University of Minnesota, School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, MN, USA
Walter E. Müller: Department of Pharmacology, ZAFES, Biocenter Niederursel, N260 Max-von-Laue Str. 9, University of Frankfurt, Germany
Gunter P. Eckert: Department of Pharmacology, ZAFES, Biocenter Niederursel, N260 Max-von-Laue Str. 9, University of Frankfurt, Germany; Corresponding author. Fax: + 49 69 798 29 374.

Journal volume & issue: Vol. 25, no. 2
pp. 438 – 445

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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