TY - JOUR
T1 - Cellular correlates of age-related endocochlear potential reduction in a mouse model
AU - Ohlemiller, Kevin K.
AU - Lett, Jaclynn M.
AU - Gagnon, Patricia M.
N1 - Funding Information:
Supported by NIH R01 DC03454 (K.K.O.), P30 DC04665, and Washington University Department of Otolaryngology.
PY - 2006/10
Y1 - 2006/10
N2 - Age-related degeneration of cochlear stria vascularis and resulting reduction in the endocochlear potential (EP) are the hallmark features of strial presbycusis, one of the major forms of presbycusis, or age-related hearing loss (ARHL) (Schuknecht, H.F., 1964. Further observations on the pathology of presbycusis. Archives of Otolaryngology 80, 369-382; Schuknecht, H.F., 1993. Pathology of the Ear. Lea and Febiger, Philadelphia; Schuknecht, H.F., Gacek, M.R., 1993. Cochlear pathology in presbycusis. Annals of Otology, Rhinology and Laryngology 102, 1-16). It is unclear whether there are multiple forms of strial ARHL having different sequences of degenerative events and different risk factors. Human temporal bone studies suggest that the initial pathology usually affects strial marginal cells, then spreads to other strial cell types. While inheritance studies support a moderate genetic influence, no contributing genes have been identified. Establishment of mouse models of strial ARHL may promote the identification of underlying genes and gene/environment interactions. We have found that BALB/cJ mice show significant EP reduction by 19 months of age. The reduction only occurs in a subset of animals. To identify key anatomical correlates of the EP reduction, we compared several cochlear lateral wall metrics in BALBs with those in C57BL/6J (B6) mice, which show little EP reduction for ages up to 26 months. Among the measures obtained, marginal cell density and spiral ligament thickness were the best predictors of both the EP decline in BALBs, and EP stability in B6. Our results indicate that the sequence of strial degeneration in BALBs is like that suggested for humans. Additional strain comparisons we have performed suggest that genes governing strial melanin production do not play a role.
AB - Age-related degeneration of cochlear stria vascularis and resulting reduction in the endocochlear potential (EP) are the hallmark features of strial presbycusis, one of the major forms of presbycusis, or age-related hearing loss (ARHL) (Schuknecht, H.F., 1964. Further observations on the pathology of presbycusis. Archives of Otolaryngology 80, 369-382; Schuknecht, H.F., 1993. Pathology of the Ear. Lea and Febiger, Philadelphia; Schuknecht, H.F., Gacek, M.R., 1993. Cochlear pathology in presbycusis. Annals of Otology, Rhinology and Laryngology 102, 1-16). It is unclear whether there are multiple forms of strial ARHL having different sequences of degenerative events and different risk factors. Human temporal bone studies suggest that the initial pathology usually affects strial marginal cells, then spreads to other strial cell types. While inheritance studies support a moderate genetic influence, no contributing genes have been identified. Establishment of mouse models of strial ARHL may promote the identification of underlying genes and gene/environment interactions. We have found that BALB/cJ mice show significant EP reduction by 19 months of age. The reduction only occurs in a subset of animals. To identify key anatomical correlates of the EP reduction, we compared several cochlear lateral wall metrics in BALBs with those in C57BL/6J (B6) mice, which show little EP reduction for ages up to 26 months. Among the measures obtained, marginal cell density and spiral ligament thickness were the best predictors of both the EP decline in BALBs, and EP stability in B6. Our results indicate that the sequence of strial degeneration in BALBs is like that suggested for humans. Additional strain comparisons we have performed suggest that genes governing strial melanin production do not play a role.
KW - Basal cells
KW - Cochlea
KW - Fibrocytes
KW - Intermediate cells
KW - Marginal cells
KW - Presbycusis
KW - Spiral ligament
KW - Stria vascularis
UR - http://www.scopus.com/inward/record.url?scp=33748302837&partnerID=8YFLogxK
U2 - 10.1016/j.heares.2006.06.012
DO - 10.1016/j.heares.2006.06.012
M3 - Article
C2 - 16901664
AN - SCOPUS:33748302837
SN - 0378-5955
VL - 220
SP - 10
EP - 26
JO - Hearing research
JF - Hearing research
IS - 1-2
ER -