Major arc mitochondrial DNA deletions in cytochrome c oxidase-deficient human cochlear spiral ganglion cells

Abstract

A statistically significant difference (p = 0.021) in the mean intensity of COX 3 immunofluorescence staining of spiral ganglion cells was observed between individuals with presbycusis and normal-hearing controls. The total mtDNA major arc deletion level was greater than the CD level in COX 3-deficient spiral ganglion cells.

Cellular Mechanisms of Age-Related Hearing Loss

“…Perhaps most compelling, a quantitative correlation was established between the level of the mtDNA4977 deletion in human temporal bone samples from ARHL patients and the severity of the hearing loss (Markaryan et al 2009 ). These authors also observed a decrease in the expression of the mitochondrial cytochrome c oxidase subunit 3 (COX3) gene in SGNs and an increase in deletions different from the mtDNA common deletion in COX3-defi cient SGNs (Markaryan et al 2010 ). Taken together, these results are consistent with a causative relationship between the accumulation of mitochondrial genomic alterations with age, mitochondrial dysfunction, and the pathogenesis of ARHL (Fig.…”

Immunohistochemical techniques for the human inner ear

“…Most of the human temporal bone banks have a collection of hematoxylin and eosin sections, from which there are remaining 9 out of 10 sections unstained that can be used for different types of staining, including IHC, histochemistry, molecular biology or proteomics (Jokay et al 1998; Kammen-Jolly et al 2001; Khetarpal 2000; Robertson et al 2001, 2006; Merchant et al 2008; Aarnisalo et al 2010; Markaryan et al 2008a, b, c, 2009a, b, c, 2010a, b, 2011; Maekawa et al 2010; Nelson and Hinojosa 2014). The tectorial membrane and Reissner’s membrane are generally well preserved, which often is not the case in paraffin-embedded or microdissected specimens.…”

“…Earlier studies utilized cytologic descriptions and graphic reconstructions of the cochlea (Guild 1921). Temporal bone science has advanced such that we are now entering a phase of methodological integration, whereby the same temporal bone can be used for light microscopy, transmission electron microscopy (TEM), immunohistochemistry (IHC), non-radioactive in situ hybridization, DNA and proteomics analysis (Aarnisalo et al 2010; Kong et al 1998; Merchant et al 2008; Ishiyama et al 2009, 2010; Lopez et al 2005a, b, 2007; Markaryan et al 2008a, b, c, 2009a, b, c, 2010a, b; Nguyen et al 2014; Richard et al 2015; Schrott-Fischer et al 1994, 2002a, b, 2007; Wackym et al 1990). The study of the human inner ear has lagged behind other areas of pathology, in large part due to the inaccessibility of the membranous labyrinth.…”

“…Thick celloidin-embedded sections (20–30 μm) of single temporal bone are kept immersed in 80 % ethylic alcohol for subsequent histological and/or immunohistochemical analysis including proteomics (Tian et al 1999; Aarnisalo et al 2010; Markaryan et al 2010a, b). Cytologic quantification of the cochlea is feasible when postmortem time is sufficiently short (Schuknecht 1993).…”

Oxidative Stresses and Mitochondrial Dysfunction in Age-Related Hearing Loss

“…Cytochrome c oxidase subunit 3 (COX3) expression was significantly diminished in SGNs from ARHL patients in comparison with age-matched normal-hearing individuals. In addition to the mtDNA common deletion, other deletions involving the mtDNA major arc contributed to the observed deficit in COX3 expression [27]. Mutations within the cytochrome c oxidase subunit 2 ( COX2 ) gene in the spiral ganglion and membranous labyrinth from archival temporal bones occur more commonly in ARHL patients relative to controls [28].…”