title: Ketamine upregulates eNOS expression in human astroglial A172 cells: Possible role in its antidepressive properties.
abstract: Ketamine is a potent anti-depressive agent. Nitric oxide plays an essential role in neuronal transmission and cerebral blood flow and has been implicated in the pathophysiology of major depressive disorder as well as cardiovascular functioning. We investigated the effect of ketamine on eNOS expression in human A172 astroglial cells. Ketamine (50-500μM) increased eNOS expression at 4-24h in a concentration-dependent manner. This effect was mediated by NMDA receptor, Akt inhibition and ERK1/2 activation and was synergistically augmented by rapamycin. The combined effect on the vascular, immune and neuronal systems may be relevant to the rapid antidepressive effect of ketamine.
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Felsenstein Medical Research Center, Petach Tikva 4941492, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: yuhas@post.tau.ac.il.
authors.forename: Yael
authors.initials: Y
authors.lastname: Yuhas
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Felsenstein Medical Research Center, Petach Tikva 4941492, Israel; Department of Pediatrics A, Schneider Children's Medical Center of Israel, Petach Tikva 4920235, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: sashkenazi@clalit.org.il.
authors.forename: Shai
authors.initials: S
authors.lastname: Ashkenazi
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Felsenstein Medical Research Center, Petach Tikva 4941492, Israel. Electronic address: Evabr@clalit.org.il.
authors.forename: Eva
authors.initials: E
authors.lastname: Berent
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petach Tikva 4941492, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Research Unit, Geha Mental Health Center, Petach Tikva 4941492, Israel. Electronic address: weizmana@gmail.com.
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016202:N-Methylaspartate; D007649:Ketamine; C056639:2-amino-5-phosphopentanoic acid; D052250:Nitric Oxide Synthase Type III; D014633:Valine; D020123:Sirolimus
keywords: Inflammation; Ketamine; Major depressive disorder; Nitric oxide; eNOS