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Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons

Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evalu...

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Autores principales: Borroni, Virginia, Kamerbeek, Constanza, Pediconi, María F., Barrantes, Francisco J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587943/
https://www.ncbi.nlm.nih.gov/pubmed/33092257
http://dx.doi.org/10.3390/molecules25204838
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author Borroni, Virginia
Kamerbeek, Constanza
Pediconi, María F.
Barrantes, Francisco J.
author_facet Borroni, Virginia
Kamerbeek, Constanza
Pediconi, María F.
Barrantes, Francisco J.
author_sort Borroni, Virginia
collection PubMed
description Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects 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 µM range. Chronic (14 days) lovastatin treatment augmented cell-surface levels of α7 and α4 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 by Western blots. At low lovastatin concentrations (10–100 nM), the increase in α4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher (0.5–1 µM) lovastatin concentrations. In contrast, neurite α7 nAChRs raised more than somatic α7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels homeostatically regulate α7 and α4 nAChR levels in a differential manner through mechanisms that depend on statin concentration and receptor localization. The neuroprotective pleomorphic effects of statins may act by reestablishing the homeostatic equilibrium.
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spelling pubmed-75879432020-10-29 Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons Borroni, Virginia Kamerbeek, Constanza Pediconi, María F. Barrantes, Francisco J. Molecules Article Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects 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 µM range. Chronic (14 days) lovastatin treatment augmented cell-surface levels of α7 and α4 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 by Western blots. At low lovastatin concentrations (10–100 nM), the increase in α4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher (0.5–1 µM) lovastatin concentrations. In contrast, neurite α7 nAChRs raised more than somatic α7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels homeostatically regulate α7 and α4 nAChR levels in a differential manner through mechanisms that depend on statin concentration and receptor localization. The neuroprotective pleomorphic effects of statins may act by reestablishing the homeostatic equilibrium. MDPI 2020-10-20 /pmc/articles/PMC7587943/ /pubmed/33092257 http://dx.doi.org/10.3390/molecules25204838 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Borroni, Virginia
Kamerbeek, Constanza
Pediconi, María F.
Barrantes, Francisco J.
Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons
title Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons
title_full Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons
title_fullStr Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons
title_full_unstemmed Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons
title_short Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons
title_sort lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587943/
https://www.ncbi.nlm.nih.gov/pubmed/33092257
http://dx.doi.org/10.3390/molecules25204838
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