Journal article
Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation
Journal of neurochemistry, Vol.108(4), pp.1057-1071
02/2009
Handle:
https://hdl.handle.net/2376/101073
PMCID: PMC4277848
PMID: 19209406
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.
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Details
- Title
- Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation
- Creators
- Woo-Yang Kim - Department of Pharmacology and Toxicology, SUNY, Buffalo, New York, USAEugene A Gonsiorek - Department of Pharmacology and Toxicology, SUNY, Buffalo, New York, USAChris Barnhart - Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon, USAMonika A Davare - Vollum Institute, Oregon Health & Science University, Portland, Oregon, USAAbby J Engebose - Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon, USAHolly Lauridsen - Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon, USADonald Bruun - Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon, USAAdam Lesiak - Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington, USAGary Wayman - Vollum Institute, Oregon Health & Science University, Portland, Oregon, USARobert Bucelli - Department of Pharmacology and Toxicology, SUNY, Buffalo, New York, USADennis Higgins - Department of Pharmacology and Toxicology, SUNY, Buffalo, New York, USAPamela J Lein - Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon, USA
- Publication Details
- Journal of neurochemistry, Vol.108(4), pp.1057-1071
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Identifiers
- 99900546613601842
- Language
- English
- Resource Type
- Journal article