Lovastatin di erentially regulates 7 and 4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons
Abstract: Neuronal 7 and 4 2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The e ects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cell...
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| Autores principales: | , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
MDPI
2020
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| Materias: | |
| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/10847 |
| Aporte de: |
| Sumario: | Abstract: Neuronal 7 and 4 2 are the predominant nicotinic acetylcholine receptor (nAChR)
subtypes found in the brain, particularly in the hippocampus. The e ects of lovastatin, an inhibitor of
cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal
cells were evaluated in the 0.01–1 M range. Chronic (14 days) lovastatin treatment augmented
cell-surface levels of 7 and 4 nAChRs, as measured by fluorescence microscopy and radioactive
ligand binding assays. This was accompanied in both cases by an increase in total protein receptor
levels as determined byWestern blots. At low lovastatin concentrations (10–100 nM), the increase
in 4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher
(0.5–1 M) lovastatin concentrations. In contrast, neurite 7 nAChRs raised more than somatic
7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels
homeostatically regulate 7 and 4 nAChR levels in a di erential manner through mechanisms that
depend on statin concentration and receptor localization. The neuroprotective pleomorphic e ects of
statins may act by reestablishing the homeostatic equilibrium. |
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