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

Zoicas I, Schumacher F, Kleuser B, Reichel M, Gulbins E, Fejtová A, Kornhuber J, Rhein C (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Cells MDPI

Book Volume: 9

Journal Issue: 5

DOI: 10.3390/cells9051244

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.

Authors with CRIS profile

Martin Reichel Department of Psychiatry and Psychotherapy Anna Fejtová Professur für Molekulare Psychiatrie Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie Cosima Rhein Department of Psychiatry and Psychotherapy

Involved external institutions

Universität Duisburg-Essen (UDE) DE Germany (DE) Universität Potsdam DE Germany (DE)

How to cite

APA:

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

MLA:

Zoicas, Iulia, et al. "The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice." Cells 9.5 (2020).

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