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Research ArticleNEUROPHARMACOLOGY

Chronic Administration of Statins Alters Multiple Gene Expression Patterns in Mouse Cerebral Cortex

Leslie N. Johnson-Anuna, Gunter P. Eckert, Jan H. Keller, Urule Igbavboa, Cornelia Franke, Thomas Fechner, Manfred Schubert-Zsilavecz, Michael Karas, Walter E. Müller and W. Gibson Wood
Journal of Pharmacology and Experimental Therapeutics February 2005, 312 (2) 786-793; DOI: https://doi.org/10.1124/jpet.104.075028
Leslie N. Johnson-Anuna
Department of Pharmacology (L.N.J.-A., U.I., W.G.W.), University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota; Department of Pharmacology (G.P.E., C.F., W.E.M.) and Department of Pharmaceutical Chemistry (J.H.K., M.S.-Z., M.K.), ZAFES Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany; and Applied Biosystems (T.F.), Applera Germany GmbH, Darmstadt, Germany
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Gunter P. Eckert
Department of Pharmacology (L.N.J.-A., U.I., W.G.W.), University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota; Department of Pharmacology (G.P.E., C.F., W.E.M.) and Department of Pharmaceutical Chemistry (J.H.K., M.S.-Z., M.K.), ZAFES Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany; and Applied Biosystems (T.F.), Applera Germany GmbH, Darmstadt, Germany
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Jan H. Keller
Department of Pharmacology (L.N.J.-A., U.I., W.G.W.), University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota; Department of Pharmacology (G.P.E., C.F., W.E.M.) and Department of Pharmaceutical Chemistry (J.H.K., M.S.-Z., M.K.), ZAFES Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany; and Applied Biosystems (T.F.), Applera Germany GmbH, Darmstadt, Germany
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Urule Igbavboa
Department of Pharmacology (L.N.J.-A., U.I., W.G.W.), University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota; Department of Pharmacology (G.P.E., C.F., W.E.M.) and Department of Pharmaceutical Chemistry (J.H.K., M.S.-Z., M.K.), ZAFES Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany; and Applied Biosystems (T.F.), Applera Germany GmbH, Darmstadt, Germany
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Cornelia Franke
Department of Pharmacology (L.N.J.-A., U.I., W.G.W.), University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota; Department of Pharmacology (G.P.E., C.F., W.E.M.) and Department of Pharmaceutical Chemistry (J.H.K., M.S.-Z., M.K.), ZAFES Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany; and Applied Biosystems (T.F.), Applera Germany GmbH, Darmstadt, Germany
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Thomas Fechner
Department of Pharmacology (L.N.J.-A., U.I., W.G.W.), University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota; Department of Pharmacology (G.P.E., C.F., W.E.M.) and Department of Pharmaceutical Chemistry (J.H.K., M.S.-Z., M.K.), ZAFES Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany; and Applied Biosystems (T.F.), Applera Germany GmbH, Darmstadt, Germany
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Manfred Schubert-Zsilavecz
Department of Pharmacology (L.N.J.-A., U.I., W.G.W.), University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota; Department of Pharmacology (G.P.E., C.F., W.E.M.) and Department of Pharmaceutical Chemistry (J.H.K., M.S.-Z., M.K.), ZAFES Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany; and Applied Biosystems (T.F.), Applera Germany GmbH, Darmstadt, Germany
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Michael Karas
Department of Pharmacology (L.N.J.-A., U.I., W.G.W.), University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota; Department of Pharmacology (G.P.E., C.F., W.E.M.) and Department of Pharmaceutical Chemistry (J.H.K., M.S.-Z., M.K.), ZAFES Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany; and Applied Biosystems (T.F.), Applera Germany GmbH, Darmstadt, Germany
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Walter E. Müller
Department of Pharmacology (L.N.J.-A., U.I., W.G.W.), University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota; Department of Pharmacology (G.P.E., C.F., W.E.M.) and Department of Pharmaceutical Chemistry (J.H.K., M.S.-Z., M.K.), ZAFES Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany; and Applied Biosystems (T.F.), Applera Germany GmbH, Darmstadt, Germany
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W. Gibson Wood
Department of Pharmacology (L.N.J.-A., U.I., W.G.W.), University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota; Department of Pharmacology (G.P.E., C.F., W.E.M.) and Department of Pharmaceutical Chemistry (J.H.K., M.S.-Z., M.K.), ZAFES Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany; and Applied Biosystems (T.F.), Applera Germany GmbH, Darmstadt, Germany
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Abstract

Statins have been reported to lower the risk of developing Alzheimer's disease; however, the mechanism of this potentially important neuroprotective action is not understood. Lowering cholesterol levels does not appear to be the primary mechanism. Statins have pleiotropic effects in addition to lowering cholesterol, and statins may act on several different pathways involving distinct gene expression patterns that would be difficult to determine by focusing on a few genes or their products in a single study. In addition, gene expression patterns may be specific to a particular statin. To understand the molecular targets of statins in brain, DNA microarrays were used to identify gene expression patterns in the cerebral cortex of mice chronically treated with lovastatin, pravastatin, and simvastatin. Furthermore, brain statin levels were determined using liquid chromatography/tandem mass spectrometry. These studies revealed 15 genes involved in cell growth and signaling and trafficking that were similarly changed by all three statins. Overall, simvastatin had the greatest influence on expression as demonstrated by its ability to modify the expression of 23 genes in addition to those changed by all three drugs. Of particular interest was the expression of genes associated with apoptotic pathways that were altered by simvastatin. Reverse transcription-polymerase chain reaction experiments confirmed the microarray findings. All three drugs were detected in the cerebral cortex, and acute experiments revealed that statins are relatively rapidly removed from the brain. These results provide new insight into possible mechanisms for the potential efficacy of statins in reducing the risk of Alzheimer's disease and lay the foundation for future studies.

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Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
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Research ArticleNEUROPHARMACOLOGY

Chronic Administration of Statins Alters Multiple Gene Expression Patterns in Mouse Cerebral Cortex

Leslie N. Johnson-Anuna, Gunter P. Eckert, Jan H. Keller, Urule Igbavboa, Cornelia Franke, Thomas Fechner, Manfred Schubert-Zsilavecz, Michael Karas, Walter E. Müller and W. Gibson Wood
Journal of Pharmacology and Experimental Therapeutics February 1, 2005, 312 (2) 786-793; DOI: https://doi.org/10.1124/jpet.104.075028

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Research ArticleNEUROPHARMACOLOGY

Chronic Administration of Statins Alters Multiple Gene Expression Patterns in Mouse Cerebral Cortex

Leslie N. Johnson-Anuna, Gunter P. Eckert, Jan H. Keller, Urule Igbavboa, Cornelia Franke, Thomas Fechner, Manfred Schubert-Zsilavecz, Michael Karas, Walter E. Müller and W. Gibson Wood
Journal of Pharmacology and Experimental Therapeutics February 1, 2005, 312 (2) 786-793; DOI: https://doi.org/10.1124/jpet.104.075028
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