TY  - JOUR
A1  - Zoicas, Iulia
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Reichel, Martin
A1  - Gulbins, Erich
A1  - Fejtova, Anna
A1  - Kornhuber, Johannes
A1  - Rhein, Cosima
T1  - The forebrain-specific overexpression of acid sphingomyelinase induces depressive-like symptoms in mice
T2  - Cells
N2  - 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-tg(fb)) 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-tg(fb) mice than in female Asm-tg(fb) 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-tg(fb) 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.
KW  - Smpd1
KW  - acid sphingomyelinase
KW  - forebrain
KW  - depressive-like behavior
KW  - anxiety-like behavior
KW  - ceramide
Y1  - 2020
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/52499
VL  - 9
IS  - 5
PB  - MDPI
CY  - Basel
ER  -