title: Protective effects of some statins on epileptogenesis and depressive-like behavior in WAG/Rij rats, a genetic animal model of absence epilepsy.
abstract: OBJECTIVE
  Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) exert cholesterol-independent pleiotropic effects that include antithrombotic, antiinflammatory, and antioxidative properties. Moreover, both in vitro and in vivo studies have shown neuroprotective, antiseizure, and antiexcitotoxic effects of statins, suggesting their potential role in the treatment of neurologic diseases. Only a few studies have investigated whether statins modulate absence seizure activity and epileptogenesis.
  
  
  METHODS
  We investigated the effects of atorvastatin (5 and 10 mg/kg/day), simvastatin (10 mg/kg/day), and pravastatin (10 and 30 mg/kg/day), given orally for 17 consecutive weeks (starting at 45 days of age), on the development of absence seizures (electroencephalography [EEG] recordings), depressive-like behavior (forced swimming test [FST]), and anxiety levels (open field test [OF]) in Wistar Albino Glaxo/Rijswijk rats (WAG/Rij) rats at the age of 6 months (1 month after suspension). WAG/Rij rats are a genetic animal model of absence epilepsy, epileptogenesis, and mild-depression comorbidity. The effects of statins were also studied after acute intraperitoneal injection for 4 h after administration of various doses in 6-months-old rats. Plasma cholesterol levels were measured throughout drug treatment.
  
  
  RESULTS
  We found that early long-term statin treatment possesses antiepileptogenic properties, reduced immobility time in the FST, and reduced anxiety in the OF, whereas they were not effective against established absence seizures when acutely administered. The observed effects were not related to changes in plasma cholesterol levels, which remained unchanged during drug treatment.
  
  
  CONCLUSIONS
  Our results suggest that statins administration might be a possible intervention and promising strategy for preventing the epileptogenesis and/or behavioral comorbidity.
authors: Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors: Rita
authors: R
authors: Citraro
authors: Serafina
authors: S
authors: Chimirri
authors: Rossana
authors: R
authors: Aiello
authors: Luca
authors: L
authors: Gallelli
authors: Francesca
authors: F
authors: Trimboli
authors: Domenico
authors: D
authors: Britti
authors: Giovambattista
authors: G
authors: De Sarro
authors: Emilio
authors: E
authors: Russo
mesh_terms: D000818:Animals; D003863:Depression / Q000188:drug therapy* / Q000235:genetics*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000235:genetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents
keywords: Atorvastatin; Cholesterol; Pleiotropic effects; Pravastatin; Simvastatin; Spike-wave discharges