Initial changes in the sensory hair-cell membrane following aminoglycoside administration in a guinea pig model

M Takumida1, J Wersäll, D Bagger-Sjöbäck

  • 1Department of Otolaryngology, Karolinsk Institutet, Karolinska Sjukhuset, Stockholm, Sweden.

Insights

Gentamicin causes sensory hair cell fusion in guinea pigs. This degeneration involves plasma membrane blebbing and actin filament breakdown, with reduced glycocalyx appearing as an initial sign.

Area of Science:

  • Ototoxicity research
  • Cell biology
  • Vestibular system science

Background:

  • Gentamicin is an aminoglycoside antibiotic.
  • Aminoglycosides are known to cause ototoxicity.
  • The precise initial cellular changes leading to hair cell death are not fully understood.

Purpose of the Study:

  • To investigate the initial structural changes in vestibular sensory hair cell plasma membranes following gentamicin exposure.
  • To classify the stages of sensory hair cell cilia degeneration induced by gentamicin.
  • To elucidate the role of the glycocalyx and plasma membrane in gentamicin-induced hair cell fusion.

Main Methods:

  • Guinea pigs were treated with gentamicin sulfate via middle ear injection.
  • Ruthenium red staining was employed to visualize sensory hair cell plasma membranes.
  • Degeneration stages were observed and classified using microscopy.

Main Results:

  • Gentamicin treatment led to degeneration of sensory hair cell cilia after 7 days.
  • Two types of fusion were identified: Type I (glycocalyx decrease) and Type II (bleb formation, glycocalyx decrease, and plasma membrane fusion).
  • Degeneration of ciliary actin filaments was also observed.

Conclusions:

  • Gentamicin impacts both the glycocalyx and plasma membrane of sensory hair cells.
  • A decrease in the glycocalyx may represent the earliest indicator of sensory hair cell fusion.
  • These findings provide insight into the mechanisms of aminoglycoside-induced ototoxicity.

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