Noise exposure potentiates the subcellular distribution of nucleotide excision repair proteins within spiral ganglion neurons

Hear Res. 2012 Dec;294(1-2):21-30. doi: 10.1016/j.heares.2012.09.001. Epub 2012 Sep 27.

Abstract

Nucleotide excision repair (NER) is a defensive mechanism that limits genomic stress through genetically distinct cascades that employs Cockayne syndrome-A (CSA), the xeroderma pigmentosum-C (XPC) and the xeroderma pigmentosum-A (XPA) proteins. Noise exposure induces stress within the spiral ganglia. Therefore, it was posited that noise exposure would mobilize NER proteins within spiral ganglion neurons. Long-Evans rats were exposed to noise (105 dB SPL/4 h) and cochlear impairment was verified (pre-post DPOAE recordings) then the animals were euthanized via intravascular perfusion for temporal bone harvesting, immunohistochemistry and quantification of intracellular protein distribution. The results revealed that under normal (quiet) conditions the majority (∼60%) of spiral ganglion neurons do not express NER proteins, however, a subpopulation (∼40%) was NER positive. The overall number of reactive neurons stayed the same following noise exposure but there was significant (p < 0.01) subcellular redistribution of NER proteins. For instance, neurons within the apex exhibited significant (p < 0.01) nuclear accumulation of CSA while neurons within the base revealed significant (p < 0.05) nuclear accumulation of XPC. This spatial heterogeneity suggests a difference in genome defense repertoire between apical and basal coils of the cochlea. Furthermore, noise exposure depleted XPA from the nucleus regardless of location along the cochlear spiral. These findings provide a novel mechanism for interpreting noise-induced neuronal stress.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • DNA Repair Enzymes / metabolism
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • Hearing Loss, Noise-Induced / metabolism*
  • Hearing Loss, Noise-Induced / pathology
  • Hearing Loss, Noise-Induced / physiopathology
  • Male
  • Neurons / pathology
  • Neurons / physiology
  • Noise / adverse effects
  • Otoacoustic Emissions, Spontaneous / physiology
  • Rats
  • Rats, Long-Evans
  • Schwann Cells / pathology
  • Schwann Cells / physiology
  • Spiral Ganglion / metabolism*
  • Spiral Ganglion / pathology
  • Spiral Ganglion / physiopathology
  • Stress, Physiological
  • Subcellular Fractions / metabolism

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • XPA protein, rat
  • XPC protein, rat
  • DNA Repair Enzymes