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- Title
The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice.
- Authors
Zoicas, Iulia; Schumacher, Fabian; Kleuser, Burkhard; Reichel, Martin; Gulbins, Erich; Fejtova, Anna; Kornhuber, Johannes; Rhein, Cosima
- 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.
- Subjects
SPHINGOMYELINASE; MICE; MENTAL depression; PROSENCEPHALON; CERAMIDES; LYSOSOMES; EOSINOPHILIA
- Publication
Cells (2073-4409), 2020, Vol 9, Issue 5, p1244
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells9051244