Simvastatin treatment induces morphology alterations and apoptosis in murine cochlear neuronal cells

Abstract

Conclusion. 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. Objectives. 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. Materials and 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.