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Molecular Brain
Published in: Molecular Brain 1/2021

Open Access 01-12-2021 | Simvastatin | Research

Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice

Authors: Yujun Guo, Guichang Zou, Keke Qi, Jin Jin, Lei Yao, Yang Pan, Wei Xiong

Published in: Molecular Brain | Issue 1/2021

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Abstract

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.
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Metadata
Title
Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice
Authors
Yujun Guo
Guichang Zou
Keke Qi
Jin Jin
Lei Yao
Yang Pan
Wei Xiong
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Molecular Brain / Issue 1/2021
Electronic ISSN: 1756-6606
DOI
https://doi.org/10.1186/s13041-021-00758-x

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