Neurotoxic 18-kDa apolipoprotein E fragment production contributes to anesthetic sevoflurane-induced tau phosphorylation and neuroinflammation in vitro.
机构:[1]Department of Anesthesiology, 117865Tianjin Medical University General Hospital, Tianjin, China.[2]Tianjin Institute of Anesthesiology, Tianjin, China.[3]Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China.四川大学华西医院
Anesthesia may induce neuronal tau phosphorylation and neurotoxicity in the developing brain. Apolipoprotein E (ApoE) may play a protective role in neuronal activity and injury repair, whereas its 18-kDa fragments are reported to induce neurodegeneration and neuroinflammation in Alzheimer's disease patients. We aimed to test the hypothesis that differences in 18-kDa ApoE fragment levels, but not full-length ApoE, in primary neurons contribute to differences in tau phosphorylation and neuroinflammation with or without sevoflurane administration. Neurons extracted from wild-type (WT), ApoE knockout (ApoE-KO), and ApoE ε3-and ε2-targeted replacement (ApoE ε3, ApoE ε2) mice were divided into control and sevoflurane groups. Neurons in the sevoflurane group were treated with 21% O2, 5% CO2, and 4.1% sevoflurane, whereas those in the control group were treated with 21% O2 and 5% CO2 only on day 5 of neuronal culture. ApoE mRNA, full-length ApoE, 18-kDa ApoE fragments, Tau-PS202/PT205 (AT8), Tau-PSer396/404 (PHF1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 and IL-1β levels were measured. The data showed that sevoflurane-induced AT8 and PHF1 increases, and TNF-α, IL-6, and IL-1β increases in WT or ApoE ε3 neurons (both expressing full-length and 18-kDa fragmented ApoE) could be mitigated in ApoE ε2 (only expressing full-length ApoE), but not in ApoE-KO neurons, indicating that differences in 18-kDa ApoE fragments, but not full-length ApoE, in primary mouse neurons contributed to differences in tau phosphorylation and neuroinflammation with or without 4.1% sevoflurane administration.
基金:
National Natural Science Foundation
of China (grant nos. 82072150 and 82001149) and Tianjin Health
Science and Technology Projects (grant no. KJ20023), the Science
and Technology Development Fund of the Tianjin Education
Commission for Higher Education (grant no. 2019KJ201), and the
Tianjin Natural Science Foundation (grant no. 20JCQNJC01050).
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2022]版:
大类|4 区医学
小类|4 区毒理学
最新[2023]版:
大类|4 区医学
小类|4 区毒理学
第一作者:
第一作者机构:[1]Department of Anesthesiology, 117865Tianjin Medical University General Hospital, Tianjin, China.[2]Tianjin Institute of Anesthesiology, Tianjin, China.[*1]Department of Anesthesia, Tianjin Medical University General Hospital, No. 154 Anshan Road, Tianjin 300052, China
共同第一作者:
通讯作者:
通讯机构:[1]Department of Anesthesiology, 117865Tianjin Medical University General Hospital, Tianjin, China.[2]Tianjin Institute of Anesthesiology, Tianjin, China.[*1]Department of Anesthesia, Tianjin Medical University General Hospital, No. 154 Anshan Road, Tianjin 300052, China
推荐引用方式(GB/T 7714):
Yu Yang,Yang M,Zhuang X,et al.Neurotoxic 18-kDa apolipoprotein E fragment production contributes to anesthetic sevoflurane-induced tau phosphorylation and neuroinflammation in vitro.[J].Human & experimental toxicology.2022,41:9603271221102519.doi:10.1177/09603271221102519.
APA:
Yu Yang,Yang M,Zhuang X,Pan J,Feng J...&Yu Yonghao.(2022).Neurotoxic 18-kDa apolipoprotein E fragment production contributes to anesthetic sevoflurane-induced tau phosphorylation and neuroinflammation in vitro..Human & experimental toxicology,41,
MLA:
Yu Yang,et al."Neurotoxic 18-kDa apolipoprotein E fragment production contributes to anesthetic sevoflurane-induced tau phosphorylation and neuroinflammation in vitro.".Human & experimental toxicology 41.(2022):9603271221102519