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Cells
Volume 9
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10.3390/cells9051244
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Article

The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice

by
Iulia Zoicas
1,
Fabian Schumacher
2,3,
Burkhard Kleuser
2,
Martin Reichel
1,†,
Erich Gulbins
3,
Anna Fejtova
1,
Johannes Kornhuber
1,‡ and
Cosima Rhein
1,4,*,‡
1
Department of Psychiatry and Psychotherapy, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
2
Department of Toxicology, University of Potsdam, 14558 Nuthetal, Germany
3
Department of Molecular Biology, University of Duisburg-Essen, 45147 Essen, Germany
4
Department of Psychosomatic Medicine and Psychotherapy, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
*
Author to whom correspondence should be addressed.
†
Current Address: Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, 10115 Berlin, Germany.
‡
These authors contributed equally to this work.
Cells 2020, 9(5), 1244; https://doi.org/10.3390/cells9051244
Received: 29 April 2020 / Revised: 14 May 2020 / Accepted: 15 May 2020 / Published: 18 May 2020
(This article belongs to the Special Issue Sphingolipids: From Pathology to Therapeutic Perspectives - A Themed Honorary Issue to Prof. Lina Obeid)
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Abstract

Human and murine studies identified the lysosomal enzyme acid sphingomyelinase (ASM) as a target for antidepressant therapy and revealed its role in the pathophysiology of major depression. In this study, we generated a mouse model with overexpression of Asm (Asm-tgfb) that is restricted to the forebrain to rule out any systemic effects of Asm overexpression on depressive-like symptoms. The increase in Asm activity was higher in male Asm-tgfb mice than in female Asm-tgfb mice due to the breeding strategy, which allows for the generation of wild-type littermates as appropriate controls. Asm overexpression in the forebrain of male mice resulted in a depressive-like phenotype, whereas in female mice, Asm overexpression resulted in a social anxiogenic-like phenotype. Ceramides in male Asm-tgfb mice were elevated specifically in the dorsal hippocampus. mRNA expression analyses indicated that the increase in Asm activity affected other ceramide-generating pathways, which might help to balance ceramide levels in cortical brain regions. This forebrain-specific mouse model offers a novel tool for dissecting the molecular mechanisms that play a role in the pathophysiology of major depression. View Full-Text
Keywords: Smpd1; acid sphingomyelinase; forebrain; depressive-like behavior; anxiety-like behavior; ceramide Smpd1; acid sphingomyelinase; forebrain; depressive-like behavior; anxiety-like behavior; ceramide
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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MDPI and ACS Style

Zoicas, I.; Schumacher, F.; Kleuser, B.; Reichel, M.; Gulbins, E.; Fejtova, A.; Kornhuber, J.; Rhein, C. The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice. Cells 2020, 9, 1244. https://doi.org/10.3390/cells9051244

AMA Style

Zoicas I, Schumacher F, Kleuser B, Reichel M, Gulbins E, Fejtova A, Kornhuber J, Rhein C. The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice. Cells. 2020; 9(5):1244. https://doi.org/10.3390/cells9051244

Chicago/Turabian Style

Zoicas, Iulia, Fabian Schumacher, Burkhard Kleuser, Martin Reichel, Erich Gulbins, Anna Fejtova, Johannes Kornhuber, and Cosima Rhein. 2020. "The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice" Cells 9, no. 5: 1244. https://doi.org/10.3390/cells9051244

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