@article{GulbinsPalmadaReicheletal.2013,
  author    = {Gulbins, Erich and Palmada, Monica and Reichel, Martin and Lueth, Anja and Boehmer, Christoph and Amato, Davide and Mueller, Christian P. and Tischbirek, Carsten H. and Groemer, Teja W. and Tabatabai, Ghazaleh and Becker, Katrin Anne and Tripal, Philipp and Staedtler, Sven and Ackermann, Teresa F. and van Brederode, Johannes and Alzheimer, Christian and Weller, Michael and Lang, Undine E. and Kleuser, Burkhard and Grassme, Heike and Kornhuber, Johannes},
  title     = {Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs},
  series = {Nature medicine},
  volume    = {19},
  journal   = {Nature medicine},
  number    = {7},
  publisher = {Nature Publ. Group},
  address   = {New York},
  issn      = {1078-8956},
  doi       = {10.1038/nm.3214},
  pages     = {934 -- +},
  year      = {2013},
  abstract  = {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.},
  language  = {en}
}