Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs

Gulbins E, Palmada M, Reichel M, Lueth A, Boehmer C, Amato D, Müller CP, Tischbirek CH, Groemer TW, Tabatabai G, Becker KA, Tripal P, Städtler S, Ackermann TF, van Brederode J, Alzheimer C, Weller M, Lang UE, Kleuser B, Grassme H, Kornhuber J (2013)

Publication Type: Journal article

Publication year: 2013

Journal

Nature Medicine Nature Publishing Group

Book Volume: 19

Pages Range: 934-938

Journal Issue: 7

DOI: 10.1038/nm.3214

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.

Authors with CRIS profile

Martin Reichel Department of Medicine 4 – Nephrology and Hypertension Davide Amato Department of Psychiatry and Psychotherapy Peter Christian Müller Professur für Suchtmedizin Philipp Tripal Lehrstuhl für Psychiatrie und Psychotherapie Sven Städtler Department of Anaesthesiology Johannes van Brederode Institut für Physiologie und Pathophysiologie Christian Alzheimer Lehrstuhl für Physiologie Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

Universität Duisburg-Essen (UDE) DE Germany (DE) Universitätsspital Zürich (USZ) CH Switzerland (CH) Universität Potsdam DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE) Universitätsspital Basel CH Switzerland (CH)

How to cite

APA:

Gulbins, E., Palmada, M., Reichel, M., Lueth, A., Boehmer, C., Amato, D.,... Kornhuber, J. (2013). Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs. Nature Medicine, 19(7), 934-938. https://doi.org/10.1038/nm.3214

MLA:

Gulbins, Erich, et al. "Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs." Nature Medicine 19.7 (2013): 934-938.

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