Abstract
Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis), a major cause of which is the loss of outer hair cells (OHCs) and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC) efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP), under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.
Highlights
Functional decline of the nervous system is a cardinal feature of normal aging [for recent review, [1,2]]
Characterization of yellow fluorescent protein (YFP)-12 mice for the medial olivocochlear (MOC) synapses on outer hair cells (OHCs) Certain neuronal populations and their synaptic terminals are well labeled in transgenic mouse lines with Yellow Fluorescent Protein (YFP) expression under the control of neuron-specific elements from the thy1 gene
OHCs receive synaptic innervation from both MOC efferent neurons and type-II spiral ganglion neurons (SGNs). These YFP-positive terminals were immunostained with an antibody against vesicular acetylcholine transporter (VAChT), a reliable cholinergic marker for MOC synapses, to determine the extent of these synapses
Summary
Functional decline of the nervous system is a cardinal feature of normal aging [for recent review, [1,2]]. Agerelated hearing loss (presbycusis) is the third most prevalent condition of elderly persons, exceeded only by arthritis and hypertension, with approximately 97% of people experiencing a decline in hearing during aging [3,4]. A pattern of progressive hearing loss typically starts at the high frequencies. This pattern is observed in C57BL/6J inbred mice, a well-studied animal model for presbycusis [5]. The age-related functional decline of hearing corresponds to a loss of outer hair cells (OHCs) and spiral ganglion neurons in the basal region of the cochlea. Little is known about possible cellular and molecular mechanisms underlying these age-related
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