Ultrastructural analysis of aminoglycoside-induced hair cell death in the zebrafish lateral line reveals an early mitochondrial response

J Comp Neurol. 2007 Jun 1;502(4):522-43. doi: 10.1002/cne.21345.


Loss of the mechanosensory hair cells in the auditory and vestibular organs leads to hearing and balance deficits. To investigate initial, in vivo events in aminoglycoside-induced hair cell damage, we examined hair cells from the lateral line of the zebrafish, Danio rerio. The mechanosensory lateral line is located externally on the animal and therefore allows direct manipulation and observation of hair cells. Labeling with vital dyes revealed a rapid response of hair cells to the aminoglycoside neomycin. Similarly, ultrastructural analysis revealed structural alteration among hair cells within 15 minutes of neomycin exposure. Animals exposed to a low, 25-microM concentration of neomycin exhibited hair cells with swollen mitochondria, but little other damage. Animals treated with higher concentrations of neomycin (50-200 microM) had more severe and heterogeneous cellular changes, as well as fewer hair cells. Both necrotic-like and apoptotic-like cellular damage were observed. Quantitation of the types of alterations observed indicated that mitochondrial defects appear earlier and more predominantly than other structural alterations. In vivo monitoring demonstrated that mitochondrial potential decreased following neomycin treatment. These results indicate that perturbation of the mitochondrion is an early, central event in aminoglycoside-induced damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Death / physiology
  • Dose-Response Relationship, Drug
  • Hair Cells, Auditory / drug effects*
  • Hair Cells, Auditory / pathology
  • Hair Cells, Auditory / physiopathology
  • Lateral Line System / drug effects*
  • Lateral Line System / pathology
  • Lateral Line System / physiopathology
  • Microscopy, Electron
  • Mitochondria / drug effects*
  • Mitochondria / pathology
  • Mitochondria / ultrastructure
  • Neomycin / toxicity*
  • Protein Synthesis Inhibitors / toxicity
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Time Factors
  • Zebrafish


  • Protein Synthesis Inhibitors
  • Neomycin