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Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice
Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence rema...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905661/ https://www.ncbi.nlm.nih.gov/pubmed/33627175 http://dx.doi.org/10.1186/s13041-021-00758-x |
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author | Guo, Yujun Zou, Guichang Qi, Keke Jin, Jin Yao, Lei Pan, Yang Xiong, Wei |
author_facet | Guo, Yujun Zou, Guichang Qi, Keke Jin, Jin Yao, Lei Pan, Yang Xiong, Wei |
author_sort | Guo, Yujun |
collection | PubMed |
description | Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins. |
format | Online Article Text |
id | pubmed-7905661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79056612021-02-25 Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice Guo, Yujun Zou, Guichang Qi, Keke Jin, Jin Yao, Lei Pan, Yang Xiong, Wei Mol Brain Research Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins. BioMed Central 2021-02-24 /pmc/articles/PMC7905661/ /pubmed/33627175 http://dx.doi.org/10.1186/s13041-021-00758-x Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Guo, Yujun Zou, Guichang Qi, Keke Jin, Jin Yao, Lei Pan, Yang Xiong, Wei Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice |
title | Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice |
title_full | Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice |
title_fullStr | Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice |
title_full_unstemmed | Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice |
title_short | Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice |
title_sort | simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905661/ https://www.ncbi.nlm.nih.gov/pubmed/33627175 http://dx.doi.org/10.1186/s13041-021-00758-x |
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