title: Simvastatin treatment induces morphology alterations and apoptosis in murine cochlear neuronal cells.
abstract: CONCLUSIONS
  Simvastatin presented neurodegenerative morphological changes and cell death via its specific inhibition of mevalonate pathway induced apoptosis in cultured cochlear neuronal cells. These findings might contribute to understanding the auditory neurobiological effects of HMG-CoA reductase inhibitors.
  
  
  OBJECTIVE
  The statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors that are widely used as anti-hypercholesterol drugs because of their beneficial cardiovascular effects. However, the effects of statins in neuronal cells are controversial, and no studies have examined the effect of statins in cochlear neuronal cells. The objective of this study was to evaluate the direct effect of simvastatin on cochlear neuronal cells and examine the mechanisms underlying these effects.
  
  
  METHODS
  Cultured mouse cochlear neuroblasts (VOT-33) and primary rat cochlear explants containing spiral ganglion neurons were treated with simvastatin in the absence or presence of mevalonate.
  
  
  RESULTS
  Simvastatin caused a loss of the cytoplasmic projections in VOT-33. In primary rat cochlear nerve cells, simvastatin decreased staining for NF200, a neuro-cytoskeletal protein. We also found that simvastatin-induced VOT-33 apoptosis, as indicated by accumulation of the sub G0/G1 fraction, DNA-ladder formation, and caspase-3 activation. The above-mentioned effects were abolished by mevalonate treatment.
authors.affiliation: Department of Laboratory Medicine, Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, Korea.
authors.forename: Do-Sim
authors.initials: DS
authors.lastname: Park
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
authors.forename: Jeong-Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Cho
authors.forename: Kui-Hyun
authors.initials: KH
authors.lastname: Yoon
authors.forename: Channy
authors.initials: C
authors.lastname: Park
authors.forename: Kijung
authors.initials: K
authors.lastname: Yun
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000924:Anticholesteremic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003056:Cochlear Nerve / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D008798:Mevalonic Acid / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000633:toxicity*; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D053148:Caspase 3; D008798:Mevalonic Acid