TY - GEN A1 - Polzin, Amin A1 - Rassaf, Tienush A1 - Boehm, Andreas A1 - Lueth, Anja A1 - Kleuser, Burkhard A1 - Zeus, Tobias A1 - Kelm, Malte A1 - Kroemer, Heyo K. A1 - Schroer, Karsten A1 - Rauch, Bernhard H. T1 - Aspirin inhibits release of platelet-derived sphingosine-1-phosphate in acute myocardial infarction T2 - INTERNATIONAL JOURNAL OF CARDIOLOGY KW - Sphingosine-1-phosphate KW - Acute coronary syndrome KW - Platelets KW - Aspirin Y1 - 2013 U6 - https://doi.org/10.1016/j.ijcard.2013.10.050 SN - 0167-5273 SN - 1874-1754 VL - 170 IS - 2 SP - E23 EP - E24 PB - ELSEVIER IRELAND LTD CY - CLARE ER - TY - JOUR A1 - Gulbins, Erich A1 - Palmada, Monica A1 - Reichel, Martin A1 - Lueth, Anja A1 - Boehmer, Christoph A1 - Amato, Davide A1 - Mueller, Christian P. A1 - Tischbirek, Carsten H. A1 - Groemer, Teja W. A1 - Tabatabai, Ghazaleh A1 - Becker, Katrin Anne A1 - Tripal, Philipp A1 - Staedtler, Sven A1 - Ackermann, Teresa F. A1 - van Brederode, Johannes A1 - Alzheimer, Christian A1 - Weller, Michael A1 - Lang, Undine E. A1 - Kleuser, Burkhard A1 - Grassme, Heike A1 - Kornhuber, Johannes T1 - Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs JF - Nature medicine N2 - Major depression is a highly prevalent severe mood disorder that is treated with antidepressants. The molecular targets of antidepressants require definition. We investigated the role of the acid sphingomyelinase (Asm)-ceramide system as a target for antidepressants. Therapeutic concentrations of the antidepressants amitriptyline and fluoxetine reduced Asm activity and ceramide concentrations in the hippocampus, increased neuronal proliferation, maturation and survival and improved behavior in mouse models of stress-induced depression. Genetic Asm deficiency abrogated these effects. Mice overexpressing Asm, heterozygous for acid ceramidase, treated with blockers of ceramide metabolism or directly injected with C16 ceramide in the hippocampus had higher ceramide concentrations and lower rates of neuronal proliferation, maturation and survival compared with controls and showed depression-like behavior even in the absence of stress. The decrease of ceramide abundance achieved by antidepressant-mediated inhibition of Asm normalized these effects. Lowering ceramide abundance may thus be a central goal for the future development of antidepressants. Y1 - 2013 U6 - https://doi.org/10.1038/nm.3214 SN - 1078-8956 VL - 19 IS - 7 SP - 934 EP - + PB - Nature Publ. Group CY - New York ER -