Animal model studies of lovastatin and simvastatin in neurodevelopmental disorders
| Lovastatin | ||||
|---|---|---|---|---|
| Model | Dose | Administration | Effect on phenotype | Reference |
| Fmr1-/y mouse | 10–100 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) AGS | Osterweil et al. (2013) |
| Fmr1-/y mouse | 10 mg/kg/d | Oral feeding 2 weeks | Rescue: visuospatial learning No rescue: exaggerated extinction of visuospatial learning | Sidorov et al. (2014) |
| Fmr1-/y mouse | 50 μm
100 mg/kg | Bath application Injection i.p. | Rescue: excessive protein synthesis AGS | Muscas et al. (2019) |
| Fmr1-/y mouse | 50 μm | Bath application | No rescue: hyperexcitability and altered gamma (visual cortical slice) | Goswami et al. (2019) |
| Fmr1-/y rat | 10 mg/kg/d | Oral feeding 2 weeks | Rescue: excessive protein synthesis Plasticity deficits (LTP PFC slice), learning impairments | Asiminas et al. (2019) |
| Ube3am-/p+ mouse | 50–100 μm
10–100 mg/kg | Bath application Injection i.p. | Rescue: hyperexcitability (hippocampal slice) AGS | Chung et al. (2018) |
| Nf1+/- mouse | 10 mg/kg/d | Injection i.p. or oral feeding | Rescue: hyperactive ERK signaling Plasticity deficit (LTP hippocampal slice) Attention deficit Impaired spatial learning (MWM) Impaired sensory gating (PPI) | Li et al. (2005) |
| Mecp2-/y mouse | 1.5 mg/kg | Injection s.c. twice weekly | Rescue: impaired locomotor activity | Buchovecky et al. (2013) |
| Ptpn11D61G/+
mouse | 10 mg/kg | Injection s.c. | Rescue: excessive Ras-ERK in brain Deficient LTP Impaired spatial learning (MWM) | Buchovecky et al. (2013) |
| En2-/- mouse | 10 mg/kg/d | Injection s.c. | Rescue: hyperactive ERK signaling No rescue: impaired spatial learning (MWM) | Provenzano et al. (2014) |
| Simvastatin | ||||
| Model | Dose | Administration | Effect on phenotype | Reference |
| Fmr1-/y mouse | 3–50 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.