A central role for the acid sphingomyelinase/ceramide system in neurogenesis and major depression.
Major depressive disorder is a severe and chronic illness with high lifetime prevalence and a high incidence of suicide as the cause of death for patients with this diagnosis. Major depressive disorder is often treated with anti-depressants. Although these drugs have been used for many years, their exact mode of action is still unknown. It has been suggested that many anti-depressants act by increasing the concentrations of serotonergic transmitters in the synaptic space. However, recent studies have examined the effects of anti-depressants on neurogenesis in the hippocampus, the restoration of hippocampal neuronal networks that may be affected by major depression, and the regulation of the hypothalamic-pituitary-adrenal axis by immature neurons in the hippocampus. Here, we present and discuss a novel hypothesis suggesting that these events are regulated by the concentrations of sphingolipids, in particular ceramide, in the hippocampus. These concepts suggest that the acid sphingomyelinase/ceramide system plays a central role in the pathogenesis of major depression and may be a novel target for anti-depressants.
Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany.|Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA.
Erich
E
Gulbins
Department of Neurology, University Hospital of the Saarland, Homburg/Saar, Germany.
Silke
S
Walter
Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany.
Katrin Anne
KA
Becker
Department of Neurology, University Hospital of the Saarland, Homburg/Saar, Germany.
Ramona
R
Halmer
Department of Neurology, University Hospital of the Saarland, Homburg/Saar, Germany.
Yang
Y
Liu
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen, Erlangen, Germany.
Martin
M
Reichel
Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA.
Michael J
MJ
Edwards
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen, Erlangen, Germany.
Christian P
CP
Müller
Department of Neurology, University Hospital of the Saarland, Homburg/Saar, Germany.
Klaus
K
Fassbender
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen, Erlangen, Germany.
Johannes
J
Kornhuber
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D002518:Ceramides / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*
D000928:Antidepressive Agents; D002518:Ceramides; D013108:Sphingomyelin Phosphodiesterase
acid sphingomyelinase; anti-depressants; cera-mide; neurogenesis