GFAP aggregates in the cochlear nerve increase the noise vulnerability of sensory cells in the organ of Corti in the murine model of Alexander disease

Neurosci Res. 2008 Sep;62(1):15-24. doi: 10.1016/j.neures.2008.05.005. Epub 2008 Jul 3.

Abstract

Outer hair cell (OHC) loss in the auditory sensory epithelium is a primary cause of noise-induced sensory-neural hearing loss (SNHL). To clarify the participation of glial cells in SNHL, we used an Alexander disease (AxD) mouse model. These transgenic mice harbor the AxD causal mutant of the human glial fibrillary acidic protein (GFAP) under the control of the mouse GFAP promoter. It is thought that GFAP aggregates compromise the function of astrocytes. In the auditory pathway, the formation of GFAP aggregates was observed only in GFAP-positive cells of the cochlear nerve. The presence of GFAP aggregates did not change auditory function at the threshold level. To assess the change in vulnerability to auditory excitotoxicity, both transgenic and control mice were treated with intense noise exposure. Auditory threshold shifts were assessed by auditory brainstem responses (ABR) at 1 and 4 weeks after noise exposure, and OHC damage was analyzed by quantitative histology at 4 weeks after exposure. Transgenic mice showed more severe ABR deficits and OHC damage, suggesting that cochlear nerve glial cells with GFAP aggregates play a role in noise susceptibility. Thus, we should focus more on the roles of cochlear nerve glial cells in SNHL.

MeSH terms

  • Acoustic Stimulation / adverse effects
  • Alexander Disease / genetics
  • Alexander Disease / metabolism*
  • Alexander Disease / physiopathology
  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Auditory Threshold / physiology
  • Cochlear Nerve / metabolism*
  • Cochlear Nerve / pathology
  • Cochlear Nerve / physiopathology
  • Disease Models, Animal
  • Evoked Potentials, Auditory, Brain Stem / physiology
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism*
  • Hearing Loss, Noise-Induced / metabolism
  • Hearing Loss, Noise-Induced / pathology
  • Hearing Loss, Noise-Induced / physiopathology
  • Hearing Loss, Sensorineural / etiology
  • Hearing Loss, Sensorineural / metabolism*
  • Hearing Loss, Sensorineural / physiopathology
  • Inclusion Bodies / genetics
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neurons, Afferent / metabolism*
  • Neurons, Afferent / pathology
  • Noise / adverse effects
  • Organ of Corti / metabolism*
  • Organ of Corti / pathology
  • Organ of Corti / physiopathology

Substances

  • Glial Fibrillary Acidic Protein