Schwann cells revert to non-myelinating phenotypes in the deafened rat cochlea.
Loss of sensory hair cells within the cochlea results in a permanent sensorineural hearing loss and initiates the gradual degeneration of spiral ganglion neurons (SGNs) - the primary afferent neurons of the cochlea. While these neurons are normally myelinated via Schwann cells, loss of myelin occurs as a precursor to neural degeneration. However, the relationship between demyelination and the status of Schwann cells in deafness is not well understood. We used a marker of peripheral myelin (myelin protein zero; P0) and a marker of Schwann cells (S100) to determine the temporal sequence of myelin and Schwann cell loss as a function of duration of deafness. Rat pups were systemically deafened for periods ranging from 2 weeks to greater than 6 months by co-administration of frusemide and gentamicin. Cochleae were cryosectioned and quantitative immunohistochemistry used to determine the extent of P0 and S100 labelling within the peripheral processes, SGN soma and their central processes within the modiolus. SGN density was also determined for each cochlear turn. P0 labelling decreased throughout the cochlea with increasing duration of deafness. The reduction in P0 labelling occurred at a faster rate than the SGN loss. In contrast, S100 labelling was not significantly reduced compared with age-matched controls in any cochlear region until 6 months post-deafening. These results suggest that Schwann cells may revert to non-myelinating phenotypes in response to deafness and exhibit greater survival traits than SGNs. The potential clinical significance of these findings for cochlear implants is discussed.
Hurley
Patricia A
PA
Department of Otolaryngology, University of Melbourne, Australia.
Crook
Jeremy M
JM
Shepherd
Robert K
RK
D000818:Animals; D000831:Animals, Newborn; D003051:Cochlea / Q000473:pathology*; D003638:Deafness / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005665:Furosemide; D005786:Gene Expression Regulation / Q000502:physiology*; D005839:Gentamicins; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D018993:Myelin P0 Protein / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000145:classification / Q000502:physiology*; D013136:Spiral Ganglion / Q000473:pathology; D013997:Time Factors
D005839:Gentamicins; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D018993:Myelin P0 Protein; D016900:Neurofilament Proteins; D009418:S100 Proteins; C051774:neurofilament protein H; D005665:Furosemide