Lovastatin attenuates sevoflurane-induced cognitive disorder in aged rats via reducing Aβ accumulation.

Abstract

As a general anesthetic widely used in surgical, sevoflurane has been shown to cause cognitive and memory deficits in the elderly. It's important to find out agents that can counteract sevoflurane-induced cognitive dysfunction. This study is aimed to investigate the effect of lovastatin on sevoflurane-induced cognitive impairment in aged rats and reveal the potential mechanisms. BV-2 cells, rat hippocampal neurons or male aged rats were exposed to 2% sevoflurane for 5 h. The cells were pretreated with 10 μM lovastatin. The rats were intraperitoneally injected with 5 mg/kg/day lovastatin for three days. The results showed that lovastatin enhanced exosomal IDE secretion from sevoflurane-exposed BV-2 cells and promoted Aβ degradation. Lovastatin treatment also inhibited the increased expressions of β-secretase 1 (BACE1) and γ-secretase in hippocampal neurons under sevoflurane exposure in vitro. In animal experiments, the discrimination index in novel object recognition test and percentage of spontaneous alternation in Y-maze test were significantly elevated after lovastatin administration. In addition, Aβ plaque area and contents of soluble Aβ1-40 and Aβ1-42 in the hippocampal tissues were decreased upon lovastatin treatment. Furthermore, lovastatin reversed sevoflurane-induced Aβ accumulation via up-regulating IDE expression, and down-regulating amyloid precursor protein (APP)-related protein expression (β-C-terminal fragment (CTF), BACE1 and γ-secretase). In conclusion, lovastatin alleviates sevoflurane-induced cognitive deficient in aged rats via promoting Aβ degradation and reducing Aβ production. Lovastatin may be beneficial in preventing anesthetic-induced cognitive impairment.

• Authors: Ying Xu, Yunxia Dong, Cong Wang, Qian Jiang, Haichao Chu, Yue Tian
• Journal: Neurochemistry international (Neurochem Int) Vol. 148 Pg. 105078 (09 2021) ISSN: 1872-9754 [Electronic] England
• PMID: 34048842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Amyloid beta-Protein Precursor
• Sevoflurane
• Lovastatin
• Amyloid Precursor Protein Secretases

Topics

• Aging (physiology)
• Amyloid Precursor Protein Secretases (metabolism)
• Amyloid beta-Protein Precursor (metabolism)
• Animals
• Cognition (drug effects)
• Cognitive Dysfunction (chemically induced, metabolism)
• Hippocampus (drug effects, metabolism)
• Lovastatin (metabolism, pharmacology)
• Mice
• Plaque, Amyloid (metabolism)
• Rats, Sprague-Dawley
• Sevoflurane (metabolism, pharmacology)
• Rats