Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation

Woo Yang Kim, Eugene A. Gonsiorek, Chris Barnhart, Monika A. Davare, Abby J. Engebose, Holly Lauridsen, Donald Bruun, Adam Lesiak, Gary Wayman, Robert Bucelli, Dennis Higgins, Pamela J. Lein

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31 Scopus citations

Abstract

Clinical and experimental evidence suggest that statins decrease sympathetic activity, but whether peripheral mechanisms involving direct actions on post-ganglionic sympathetic neurons contribute to this effect is not known. Because tonic activity of these neurons is directly correlated with the size of their dendritic arbor, we tested the hypothesis that statins decrease dendritic arborization in sympathetic neurons. Oral administration of atorvastatin (20 mg/kg/day for 7 days) significantly reduced dendritic arborization in vivo in sympathetic ganglia of adult male rats. In cultured sympathetic neurons, statins caused dendrite retraction and reversibly blocked bone morphogenetic protein-induced dendritic growth without altering cell survival or axonal growth. Supplementation with mevalonate or isoprenoids, but not cholesterol, attenuated the inhibitory effects of statins on dendritic growth, whereas specific inhibition of isoprenoid synthesis mimicked these statin effects. Statins blocked RhoA translocation to the membrane, an event that requires isoprenylation, and constitutively active RhoA reversed statin effects on dendrites. These observations that statins decrease dendritic arborization in sympathetic neurons by blocking RhoA activation suggest a novel mechanism by which statins decrease sympathetic activity and protect against cardiovascular and cerebrovascular disease.

Original languageEnglish
Pages (from-to)1057-1071
Number of pages15
JournalJournal of Neurochemistry
Volume108
Issue number4
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

Keywords

  • Dendrites
  • Isoprenoids
  • RhoA
  • Statins
  • Sympathetic neurons

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    Kim, W. Y., Gonsiorek, E. A., Barnhart, C., Davare, M. A., Engebose, A. J., Lauridsen, H., Bruun, D., Lesiak, A., Wayman, G., Bucelli, R., Higgins, D., & Lein, P. J. (2009). Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation. Journal of Neurochemistry, 108(4), 1057-1071. https://doi.org/10.1111/j.1471-4159.2008.05854.x