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Lovastatin attenuates sevoflurane-induced cognitive disorder in aged rats via reducing Aβ accumulation.
- Source :
-
Neurochemistry International . Sep2021, Vol. 148, pN.PAG-N.PAG. 1p. - Publication Year :
- 2021
-
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 Aβ 1-40 and Aβ 1-42 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. • 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *RATS
*LOVASTATIN
*AMYLOID beta-protein precursor
*COGNITION disorders
Subjects
Details
- Language :
- English
- ISSN :
- 01970186
- Volume :
- 148
- Database :
- Academic Search Index
- Journal :
- Neurochemistry International
- Publication Type :
- Academic Journal
- Accession number :
- 151365166
- Full Text :
- https://doi.org/10.1016/j.neuint.2021.105078