Lovastatin attenuates sevoflurane-induced cognitive disorder in aged rats via reducing Aβ accumulation. (September 2021)

• Record Type: Journal Article
• Authors: Xu, Ying; Dong, Yunxia; Wang, Cong; Jiang, Qian; Chu, Haichao; Tian, Yue
• Is Part Of: Neurochemistry international. Volume 148(2021)
• Publication Date: 2021-09
• Subjects: Sevoflurane -- Lovastatin -- Cognition -- Aβ -- Insulin-degrading enzyme; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2021.105078
• Languages: English
• ISSNs: 0197-0186

Abstract

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. Highlights: Lovastatin promoted Aβ degradation in vitro and in vivo. Lovastatin improved sevoflurane-induced cognitive disorder. Lovastatin increased IDE secretion from BV-2 cells via an exosome secretory pathway.