Table 1

Animal model studies of lovastatin and simvastatin in neurodevelopmental disorders

ModelDoseAdministrationEffect on phenotypeReference
Fmr1-/y mouse10–100 μm
30–100 mg/kg
10 mg/kg/d
Bath application
Injection i.p.
Oral feeding 2 d
Rescue: excessive protein synthesis
Exaggerated plasticity (mGluR-LTD)
Epileptogenesis (hippocampal slice)
Hyperexcitability (visual cortical slice)
Osterweil et al. (2013)
Fmr1-/y mouse10 mg/kg/dOral feeding 2 weeksRescue: visuospatial learning
No rescue: exaggerated extinction of visuospatial learning
Sidorov et al. (2014)
Fmr1-/y mouse50 μm
100 mg/kg
Bath application
Injection i.p.
Rescue: excessive protein synthesis AGS Muscas et al. (2019)
Fmr1-/y mouse50 μm Bath applicationNo rescue: hyperexcitability and altered gamma (visual cortical slice) Goswami et al. (2019)
Fmr1-/y rat10 mg/kg/dOral feeding 2 weeksRescue: excessive protein synthesis Plasticity deficits (LTP PFC slice),
learning impairments
Asiminas et al. (2019)
Ube3am-/p+ mouse50–100 μm
10–100 mg/kg
Bath application
Injection i.p.
Rescue: hyperexcitability (hippocampal slice)
Chung et al. (2018)
Nf1+/- mouse10 mg/kg/dInjection i.p. or oral feedingRescue: hyperactive ERK signaling Plasticity deficit (LTP hippocampal slice)
Attention deficit
Impaired spatial learning (MWM)
Impaired sensory gating (PPI)
Li et al. (2005)
Mecp2-/y mouse1.5 mg/kgInjection s.c. twice weeklyRescue: impaired locomotor activity Buchovecky et al. (2013)
10 mg/kgInjection s.c.Rescue: excessive Ras-ERK in brain
Deficient LTP
Impaired spatial learning (MWM)
Buchovecky et al. (2013)
En2-/- mouse10 mg/kg/dInjection s.c.Rescue: hyperactive ERK signaling
No rescue: impaired spatial learning (MWM)
Provenzano et al. (2014)
ModelDoseAdministrationEffect on phenotypeReference
Fmr1-/y mouse3–50 mg/kg
0.1–5 μm
Injection i.p.
Bath application
No rescue: AGS
Worsening: Excessive protein synthesis
Muscas et al. (2019)
  • Studies using animal models of neurodevelopmental disorders have tested the impact of lovastatin on multiple phenotypes. Ours is the only study of simvastatin in a neurodevelopmental animal model.

  • i.p.: intraperitoneal, s.c.: subcutaneous, mGluR-LTD: metabotropic glutamate receptor stimulated long-term depression, LTP: long-term potentiation, PFC: prefrontal cortex, ERK: extracellular-regulated kinase, MWM: Morris Water Maze, PPI: pre-pulse inhibition.