Structural aging of the utricular macula in mice

Abstract

CBA/CaJ is a mouse strain that has no known genetic mutations affecting the inner ear, thereby serving as a control model for auditory and vestibular aging. C57BL/6J and CE/J mouse strains carry the genetic mutation Cdh23753A (Ahl), which results in early-onset, age-related hearing loss. CBA/CaJ and CE/J mice both exhibit an age-related decline in gravity receptor function, with function declining at a considerably faster rate in the CE/J strain than in the CBA/CaJ strain. C57BL/6J mice exhibit minimal declines in gravity receptor function with age. The purpose of this study was to characterize the effect of age on three structures within the utricle of the inner ear; hair cells, synaptic ribbons, and post-synaptic receptor sites - all of which are critical to sensory transduction, and compare structural aging with gravity receptor functional data across the lifespan. Utricles were dissected, stained with CtBP2 (marker for hair cell nuclei and synaptic ribbons) and Shank1a (marker for post-synaptic receptor sites), and imaged using confocal microscopy. Structures were quantified and averaged over four distinct areas of the utricle at several age points across the lifespan. For the CBA/CaJ strain, the number of hair cells and CtBP2 per hair cell declined by the oldest age group while Shank1a and synaptic colocalization counts per hair cell remained relatively stable across the lifespan. All structures measured for the C57BL/6J and CE/J strains were maintained with age. When compared with aging gravity receptor functional data, structural results for the CBA/CaJ and C57BL/6J strains were relatively consistent with their corresponding function. Maintenance of structural elements as observed for CE/J mice is disparate from severe age-related gravity receptor dysfunction observed for this strain. Overall, results suggest that presynaptic elements may play a role in normal age-related gravity receptor dysfunction while the presence of Ahl does not appear to result in a significant loss of vestibular structure with age. Additional influences must be responsible for age-related declines in gravity receptor function observed in the CE/J strain.