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Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation
Author(s) -
Kim WooYang,
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.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05854.x
Subject(s) - rhoa , endocrinology , medicine , dendritic spine , atorvastatin , sympathetic nervous system , dendrite (mathematics) , chemistry , biology , pharmacology , microbiology and biotechnology , signal transduction , blood pressure , geometry , mathematics , hippocampal formation
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.