Zoicas I, Schumacher F, Kleuser B, Reichel M, Gulbins E, Fejtová A, Kornhuber J, Rhein C (2020)
Publication Type: Journal article
Publication year: 2020
Book Volume: 9
Journal Issue: 5
DOI: 10.3390/cells9051244
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.
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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