Lovastatin, not Simvastatin, Corrects Core Phenotypes in the Fragile X Mouse Model.
eNeuro
; 6(3)2019.
Article
em En
| MEDLINE
| ID: mdl-31147392
ABSTRACT
The cholesterol-lowering drug lovastatin corrects neurological phenotypes in animal models of fragile X syndrome (FX), a commonly identified genetic cause of autism and intellectual disability (ID). The therapeutic efficacy of lovastatin is being tested in clinical trials for FX; however, the structurally similar drug simvastatin has been proposed as an alternative due to an increased potency and brain penetrance. Here, we perform a side-by-side comparison of the effects of lovastatin and simvastatin treatment on two core phenotypes in Fmr1-/y mice versus WT littermates excessive hippocampal protein synthesis and susceptibility to audiogenic seizures (AGSs). We find that simvastatin does not correct excessive hippocampal protein synthesis in the Fmr1-/y hippocampus at any dose tested. In fact, simvastatin significantly increases protein synthesis in both Fmr1-/y and WT. Moreover, injection of simvastatin does not reduce AGS in the Fmr1-/y mouse, while lovastatin significantly reduces AGS incidence and severity versus vehicle-treated animals. These results show that unlike lovastatin, simvastatin does not correct core phenotypes in the Fmr1-/y mouse model.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Lovastatina
/
Sinvastatina
/
Síndrome do Cromossomo X Frágil
/
Anticolesterolemiantes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
ENeuro
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido