Abstract
Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs) is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family.
Highlights
Functional decline of the nervous system is a cardinal feature of aging, yet the cellular mechanisms underlying this decline are unknown
Over-expression of human Bcl-2 in the hair cells and spiral ganglion neurons The transgenic mice used in this study express human Bcl-2 under the control of the neuron-specific enolase promoter [33]
Inner hairs cells and some spiral ganglion neurons (SGNs) from transgenic Bcl-2 overexpressing mice were immunoreactive for calretinin, and hair cells and SGNs from the same sample expressed human Bcl-2 (Figure 1B)
Summary
Functional decline of the nervous system is a cardinal feature of aging, yet the cellular mechanisms underlying this decline are unknown. In the cochlea, age-related loss of auditory neurons, such as hair cells and spiral ganglion neurons (SGNs), is a major cause of presbycusis [4]. Age-related loss of hair cells and SGNs is observed in the inbred C57BL/6J mouse, an established animal model for presbycusis [5,6,7]. Despite this knowledge, the exact mechanisms underlying agerelated death of hair cells and SGNs are unknown [8,9,10,11]. Cells die by either passive or active processes [12].
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