Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1783600276055261184 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7587943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT borronivirginia lovastatindifferentiallyregulatesa7anda4neuronalnicotinicacetylcholinereceptorlevelsinrathippocampalneurons AT kamerbeekconstanza lovastatindifferentiallyregulatesa7anda4neuronalnicotinicacetylcholinereceptorlevelsinrathippocampalneurons AT pediconimariaf lovastatindifferentiallyregulatesa7anda4neuronalnicotinicacetylcholinereceptorlevelsinrathippocampalneurons AT barrantesfranciscoj lovastatindifferentiallyregulatesa7anda4neuronalnicotinicacetylcholinereceptorlevelsinrathippocampalneurons |