title: Anesthetic sevoflurane reduces levels of hippocalcin and postsynaptic density protein 95.
abstract: 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.
authors.affiliation: Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA, 02129-2060, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Dong
authors.forename: Chen
authors.initials: C
authors.lastname: Zhou
authors.forename: Yiying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhongcong
authors.initials: Z
authors.lastname: Xie
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000378:metabolism*; D051597:Hippocalcin / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008738:Methyl Ethers / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000077149:Sevoflurane
chemical_list: D000777:Anesthetics; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C496692:Hpca protein, mouse; D008565:Membrane Proteins; D008738:Methyl Ethers; D016194:Receptors, N-Methyl-D-Aspartate; D051597:Hippocalcin; D000077149:Sevoflurane; D051528:Guanylate Kinases; D002118:Calcium