Genetic disruption of fractalkine signaling leads to enhanced loss of cochlear afferents following ototoxic or acoustic injury

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Cochlear hair cells are vulnerable to a variety of insults like acoustic trauma and ototoxic drugs. Such injury can also lead to degeneration of spiral ganglion neurons (SGNs), but this occurs over a period of months to years. Neuronal survival is necessary for the proper function of cochlear prosthetics, therefore, it is of great interest to understand the mechanisms that regulate neuronal survival in deaf ears. We have recently demonstrated that selective hair cell ablation is sufficient to attract leukocytes into the spiral ganglion, and that fractalkine signaling plays a role in macrophage recruitment and in the survival of auditory neurons. Fractalkine (CX 3 CL1), a chemokine that regulates adhesion and migration of leukocytes is expressed by SGNs and signals to leukocytes via its receptor CX 3 CR1. The present study has extended the previous findings to more clinically relevant conditions of sensorineural hearing loss by examining the role of fractalkine signaling after aminoglycoside ototoxicity or acoustic trauma. Both aminoglycoside treatment and acoustic overstimulation led to the loss of hair cells as well as prolonged increase in the numbers of cochlear leukocytes. Lack of CX 3 CR1 did not affect macrophage recruitment after injury, but resulted in increased loss of SGNs and enhanced expression of the inflammatory cytokine interleukin-1β, when compared to mice with intact CX 3 CR1. These data indicate that the dysregulation of macrophage response caused by the absence of CX 3 CR1 may contribute to inflammation-mediated neuronal loss in the deafened ear, suggesting a key role for inflammation in the long-term survival of target-deprived afferent neurons.

Original languageEnglish
Pages (from-to)824-835
Number of pages12
JournalJournal of Comparative Neurology
Volume526
Issue number5
DOIs
StatePublished - Apr 1 2018

Keywords

  • RRID: AB_10013626
  • RRID: AB_221569
  • RRID: AB_2313773
  • RRID: AB_2314897
  • RRID: IMSR_JAX:005582
  • RRID: SCR_002668
  • fractalkine
  • hearing loss
  • inflammation
  • interleukin-1β
  • macrophages
  • spiral ganglion neurons

Fingerprint Dive into the research topics of 'Genetic disruption of fractalkine signaling leads to enhanced loss of cochlear afferents following ototoxic or acoustic injury'. Together they form a unique fingerprint.

  • Cite this