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

IF 0.5 4区 医学 Q4 NEUROSCIENCES
Zhenghua Wu, Kuan Huang
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引用次数: 0

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.

Abstract Image

七氟醚诱导的 BRCA1 减少会加剧淀粉样蛋白-β的神经毒性
摘要吸入麻醉剂七氟醚被广泛报道会诱发神经毒性,但其潜在机制却不甚明了。在此,我们研究了七氟烷麻醉会导致学习和记忆功能下降,尤其是在老年小鼠中。研究发现,七氟烷会导致海马中的 BRCA1 下调。暴露于七氟烷会导致体外 BRCA1 减少,同时伴随着 β 淀粉样前体蛋白和 β 淀粉样蛋白的增加。Aβ1-42 可抑制 BRCA1 蛋白的丰度,但不能抑制 mRNA,而且 BRCA1 不能改变 β 淀粉样蛋白的表达。此外,还观察到 BRCA1 参与了七氟烷诱导的神经毒性,因为 BRCA1 敲除会加剧而过表达则会减轻七氟烷诱导的神经细胞活力下降。我们的研究结果首次证明了BRCA1在七氟烷诱导的神经毒性中的重要作用,而β-淀粉样蛋白可能是BRCA1与七氟烷之间的纽带。
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来源期刊
Neurochemical Journal
Neurochemical Journal 医学-神经科学
自引率
20.00%
发文量
40
审稿时长
>12 weeks
期刊介绍: Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components. The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.
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