Aging Cochlea Research Articles

Endonuclease cleavage of DNA in the aged cochlea of Mongolian gerbil

Apoptosis is the most common form of physiological cell death, plays an important role in a variety of physiological and pathological situations, and is characterized by an endonuclease activation. Aged gerbils (24-month-old) showed a significant elevation of the distortion product otoacoustic emission (DPOAE) threshold and a significant decrease of the DPOAE level as compared to young gerbils (3- to 6-month-old), suggesting a disturbance of the outer hair cell in the aged cochlea. Furthermore, the endocochlear potential in the aged (15–75 mV) was apparently lower than that in the young (80–90 mV), indicating strial damage with aging. A terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method demonstrated the presence of the DNA fragmentation predominantly in the outer hair cells and spiral ganglion cells. These changes were sporadically observed in the inner hair cells and supporting cells. TUNEL positive cells were markedly observed in some aged gerbils showing deterioration in cochlear function, which may suggest the individual variability of presbycusis. On the other hand, the strial cells showed a marked atrophy, but no DNA fragmentation. These findings suggest that the aged change in the outer hair cells and spiral ganglion cells involves an apoptotic death pathway. However, strial atrophy with aging seems to be unrelated to apoptosis.

Histopathologic observations of the aging gerbil cochlea

Age-related histopathologic changes were examined in cochleas from 17 gerbils born and kept in a quiet environment until near the end of their life expectancy. Hearing loss varied greatly as did the loss of outer hair cells (OHC). Inner hair cells (IHC) were seldom missing even in cochleas with severe hearing losses. Flask- and spherical-shaped OHCs were frequently seen in the apical turn. Stereocilia were usually present and orderly on OHCs, but the tallest row of stereocilia on IHCs was often disarrayed and sometimes missing. Alterations in supporting cells were sometimes present in regions of extensive OHC loss. Although pillar cells were seldom missing, the nuclei of outer pillar cells were commonly displaced from their normal basal position. The density of radial fibers appeared similar to that in young gerbils except in the apical turn of one old ear where a marked loss of radial fibers occurred without an attendant loss of IHCs. All of the quiet-aged cochleas showed a characteristic clustering of epithelial cells lining the scala media surface of Reissner's membrane. This structural rearrangement was not accompanied by a significant decrease in the total number of cells forming Reissner's membrane and did not appear to be associated with hearing loss. The findings confirm and extend earlier work showing that several different types of cells are susceptible to histopathologic changes in old ears. The extent of histopathologic changes varied widely as did the degree of hearing loss in animals with a restricted genetic background and maintained under carefully controlled environmental conditions. It was not possible, based on these initial findings, to relate specific structural to specific functional changes in the aging cochlea. Further light and electron microscopic analysis of other regions from these aged cochleas may provide more conclusive data.

The pathophysiology of presbyacusis: Does the aging cochlea need a jump start?

The Mongolian gerbil is used as an animal model to study the pathophysiology underlying presbyacusis. Gerbils are raised from birth in a quiet vivarium or are exposed to a long-duration wideband noise (0.5–4.0 kHz for 1–2 years at 85 dB SPL) at some time during their life. Quiet-aged ears have thresholds that are increased somewhat, especially above 4 kHz, but nonlinearities such as otoacoustic emissions and two-tone suppression are present and are largely unaffected by the aging process. Morphologically, hair cells in quiet-aged animals are highly conserved, whereas the lateral wall system degenerates, resulting in a decreased endocochlear potential (EP). Current injection to bolster the EP in these quiet-aged ears can enhance the response to low- and high-level stimuli. Noise-aged ears, while also showing increased thresholds, can be differentiated from their quiet-aged counterparts by a lack of nonlinear phenomena. Two-tone suppression is absent as are otoacoustic emissions. Thus, aging in quiet or in noise can have very different outcomes with regard to overall peripheral function, even when the respective audibility curves are similar. [Work supported by NIH P01 DC00422.]

Fibronectin‐like immunoreactivity of the basilar membrane of young and aged rats

Dysfunction of cochlear mechanics has been hypothesized to be a source of age-related hearing loss and the basilar membrane mass and stiffness contribute to normal cochlear mechanics. Fibronectin, a large, extracellular matrix protein and a major component of the basilar membrane, may contribute to both the mass and stiffness of the membrane. Mesothelial cells underlying the basilar membrane may produce the fibronectin and also contribute to the mass of the membrane. Changes in either the fibronectin or the mesothelial cells might, therefore, have an effect on cochlear mechanics. In order to assess basilar membrane changes in aged animals, young adult (2-4 months) and aged (24-26 months) Sprague-Dawley rats were evaluated for the presence of fibronectin-like protein and mesothelial cells. The basilar membrane in the young animals had strong fibronectin-like immunoreactivity throughout its length. The old animals, on the other hand, showed normal fibronectin immunoreactivity in the basilar membrane of the basal turn, but little or no reactivity in the apical cochlear turn. The number of mesothelial cells was reduced throughout the length of the membrane in aged animals, with the greatest loss in the basal turn (60% fewer cells). These two degenerative changes, which appear to be independent of each other, may contribute to the observed threshold shifts in aged cochleas.

Cochlear degeneration in aged rats of four strains

Animals with various degrees of inbreeding, some of which are albino, are frequently used in biological research. Albinos do not produce melanin and it is therefore absent from the cochlea. While the function of melanin is unknown, it has been hypothesized that it is involved in cochlear homeostasis. It is possible then, that age-related degeneration may be affected by the presence or absence of melanin. We therefore evaluated young (2–6 months old) and aged (24–36 months old) cochleas in 4 different rat strains: albino Fischer 344 and Lewis rats and pigmented Lewis-Brown Norway F1 rats and Brown Norway rats. Cochlear morphology was the same across all strains of young adult animals with the exception that the pigmented animals had small, darkly stained granules in the stria vascularis. The aged pigmented animals all had large granules as well as small ones. Degeneration of spiral ganglion cells in the apical region of the ganglion had occured in the old animals of all strains. Strial degeneration at the apex was also present in aged animals. There was no correlation between the presence or absence of melanin and the magnitude of cochlear degenerative changes in the aged animals. The presence or absence of melanin therefore, appears to have no effect on cochlear degeneration in the aged rat cochlea.

Histologic changes in the aging cochlea.

Histologic changes in the aging cochlea.