Reduction of BRCA1 Induced by Sevoflurane Exacerbates the Neurotoxicity of Amyloid-β

Abstract

Inhaled anesthetic sevoflurane is widely reported to induce neurotoxicity, whereas the underlying mechanism is less elucidated. Here, we investigated that sevoflurane anesthesia causes a decrease in learning and memory functions, especially in aged mice. BRCA1 was found to be downregulated by sevoflurane administration in the hippocampus. Sevoflurane exposure led to decreased BRCA1 in vitro, accompanied by an increase of β-amyloid precursor protein and β-amyloid. Aβ1-42 suppressed the protein abundance of BRCA1 but not mRNA, and BRCA1 could not alter the expression of β-amyloid. Furthermore, BRCA1 was observed to participate in the neurotoxicity induced by sevoflurane, since BRCA1 knockdown exacerbated, while overexpression mitigated sevoflurane-induced decrease of cell viability of neuronal cells. Our results demonstrated for the first time that the vital role of BRCA1 in sevoflurane-induced neurotoxicity, and β‑amyloid might serve as the link between BRCA1 and sevoflurane.