| First Author | Zoicas I | Year | 2020 |
| Journal | Cells | Volume | 9 |
| Issue | 5 | PubMed ID | 32443534 |
| Mgi Jnum | J:304227 | Mgi Id | MGI:6694435 |
| Doi | 10.3390/cells9051244 | Citation | Zoicas I, et al. (2020) The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice. Cells 9(5):1244 |
| abstractText | 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. |
