RT Journal Article SR Electronic T1 Lovastatin, not Simvastatin, Corrects Core Phenotypes in the Fragile X Mouse Model JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0097-19.2019 DO 10.1523/ENEURO.0097-19.2019 VO 6 IS 3 A1 Muscas, Melania A1 Louros, Susana R. A1 Osterweil, Emily K. YR 2019 UL http://www.eneuro.org/content/6/3/ENEURO.0097-19.2019.abstract AB 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.