Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation
| العنوان: | Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation |
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| المؤلفون: | Woo Yang Kim, Abby J. Engebose, Adam Lesiak, Robert Bucelli, Dennis Higgins, Gary A. Wayman, Monika A. Davare, Eugene A. Gonsiorek, Holly M. Lauridsen, Donald A. Bruun, Pamela J. Lein, Chris Barnhart |
| المصدر: | Journal of Neurochemistry. 108:1057-1071 |
| بيانات النشر: | Wiley, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Male, Sympathetic nervous system, medicine.medical_specialty, Statin, RHOA, medicine.drug_class, Atorvastatin, Mevalonic Acid, Blood Pressure, Mevalonic acid, Biology, Biochemistry, Article, Rats, Sprague-Dawley, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Heart Rate, Internal medicine, medicine, Animals, cardiovascular diseases, Cell Shape, Cells, Cultured, Prenylation, Ganglia, Sympathetic, Terpenes, Cholesterol, nutritional and metabolic diseases, Cell Differentiation, Dendrites, Dendritic cell, Rats, Enzyme Activation, Protein Transport, medicine.anatomical_structure, Endocrinology, nervous system, chemistry, Bone Morphogenetic Proteins, biology.protein, lipids (amino acids, peptides, and proteins), Neuron, Hydroxymethylglutaryl-CoA Reductase Inhibitors, rhoA GTP-Binding Protein, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1471-4159 0022-3042 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a7a4b8b38da327d96a43c355e79f8211 https://doi.org/10.1111/j.1471-4159.2008.05854.x |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a7a4b8b38da327d96a43c355e79f8211 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14714159 00223042 |
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