Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice

Molecular Brain

Guichang Zou¹  Lei Yao¹  Yujun Guo¹  Jin Jin¹  Wei Xiong²  Keke Qi³  Yang Pan³ 

[1] Department of Neurosurgery, Institute On Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences At the Microscale, University of Science and Technology of China, 230026, Hefei, China;Department of Neurosurgery, Institute On Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences At the Microscale, University of Science and Technology of China, 230026, Hefei, China;Advanced Innovation Center for Human Brain Protection, Capital Medical University, 100070, Beijing, China;Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 200031, Shanghai, China;National Synchrotron Radiation Laboratory, University of Science and Technology of China, 230029, Hefei, China;

关键词: Simvastatin;    Cholesterol;    Hippocampus;    Cognition;    Mass spectrometry imaging;   

DOI  :  10.1186/s13041-021-00758-x

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY