Sevoflurane, the commonly used inhalation anesthetic in children, has been shown to enhance cytosolic calcium levels and induce cognitive impairment in young mice. However, the downstream consequences of the sevoflurane-induced elevation in cytosolic calcium levels and the upstream mechanisms of the sevoflurane-induced cognitive impairment remain largely to be determined. Hippocalcin is one of the neuronal calcium sensor proteins, and also binds to postsynaptic density protein 95 (PSD-95). We therefore set out to determine the effects of sevoflurane on the levels of hippocalcin and PSD-95 in vitro and in vivo. Hippocampus neurons from mice and 6-day-old mice were treated with 4.1 % sevoflurane for 6 h or 3 % sevoflurane 2 h daily for 3 days, respectively. We then measured the levels of hippocalcin and PSD-95, and assessed whether BAPTA, an intracellular calcium chelator, and memantine, a partial antagonist of the NMDA receptor, could inhibit the sevoflurane's effects. We found that sevoflurane decreased the levels of hippocalcin and PSD-95 in the neurons; and decreased the levels of hippocalcin and PSD-95 in the hippocampus of mice immediately after the anesthesia, but only the PSD-95 levels three weeks after the anesthesia. BAPTA inhibited the sevoflurane's effects in the neurons. Memantine attenuated the sevoflurane-induced reductions in the levels of hippocalcin and PSD-95, as well as the sevoflurane-induced cognitive impairment in mice. These data suggested that sevoflurane decreased the levels of hippocalcin and PSD-95, which could serve as one of bridge mechanisms between the sevoflurane-induced elevation of cytosolic calcium levels and the sevoflurane-induced cognitive impairment.
基金：
National Institutes of Health, Bethesda, Maryland [R21AG038994, R01 GM088801, R01 AG041274]; Alzheimer's Association, Chicago, Illinois; Cure Alzheimer's Fund, Wellesley, Massachusetts
第一作者单位：[1]Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA[2]Harvard Univ, Sch Med, Charlestown, MA 02129 USA[3]Huazhong Univ Sci & Technol, Dept Anesthesiol, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China
通讯作者：
通讯机构：[1]Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA[2]Harvard Univ, Sch Med, Charlestown, MA 02129 USA[*1]Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4310, Charlestown, MA 02129 USA
推荐引用方式(GB/T 7714)：
Zhang Jie,Dong Yuanlin,Zhou Chen,et al.Anesthetic Sevoflurane Reduces Levels of Hippocalcin and Postsynaptic Density Protein 95[J].MOLECULAR NEUROBIOLOGY.2015,51(3):853-863.doi:10.1007/s12035-014-8746-1.
APA：
Zhang, Jie,Dong, Yuanlin,Zhou, Chen,Zhang, Yiying&Xie, Zhongcong.(2015).Anesthetic Sevoflurane Reduces Levels of Hippocalcin and Postsynaptic Density Protein 95.MOLECULAR NEUROBIOLOGY,51,(3)
MLA：
Zhang, Jie,et al."Anesthetic Sevoflurane Reduces Levels of Hippocalcin and Postsynaptic Density Protein 95".MOLECULAR NEUROBIOLOGY 51..3(2015):853-863
