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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 (US)
Pages (from-to)1057-1071
Number of pages15
JournalJournal of Neurochemistry
Volume108
Issue number4
DOIs
StatePublished - Feb 2009

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Neuronal Plasticity
Neurons
Rats
Chemical activation
Terpenes
Dendrites
Growth
Prenylation
Cerebrovascular Disorders
Mevalonic Acid
Sympathetic Ganglia
Bone Morphogenetic Proteins
Oral Administration
Cell Survival
Cardiovascular Diseases
Cholesterol
Cells
Membranes

Keywords

  • Dendrites
  • Isoprenoids
  • RhoA
  • Statins
  • Sympathetic neurons

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation. / Kim, Woo Yang; Gonsiorek, Eugene A.; Barnhart, Chris; Davare, Monika A.; Engebose, Abby J.; Lauridsen, Holly; Bruun, Donald; Lesiak, Adam; Wayman, Gary; Bucelli, Robert; Higgins, Dennis; Lein, Pamela J.

In: Journal of Neurochemistry, Vol. 108, No. 4, 02.2009, p. 1057-1071.

Research output: Contribution to journalArticle

Kim, WY, Gonsiorek, EA, Barnhart, C, Davare, MA, Engebose, AJ, Lauridsen, H, Bruun, D, Lesiak, A, Wayman, G, Bucelli, R, Higgins, D & Lein, PJ 2009, 'Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation', Journal of Neurochemistry, vol. 108, no. 4, pp. 1057-1071. https://doi.org/10.1111/j.1471-4159.2008.05854.x
Kim, Woo Yang ; Gonsiorek, Eugene A. ; Barnhart, Chris ; Davare, Monika A. ; Engebose, Abby J. ; Lauridsen, Holly ; Bruun, Donald ; Lesiak, Adam ; Wayman, Gary ; Bucelli, Robert ; Higgins, Dennis ; Lein, Pamela J. / Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation. In: Journal of Neurochemistry. 2009 ; Vol. 108, No. 4. pp. 1057-1071.
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