Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure

• Published in: Scientific reports Vol. 6; no. 1; p. 24907
• Main Authors: Suzuki, Jun, Corfas, Gabriel, Liberman, M. Charles
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.04.2016; Nature Publishing Group
• Subjects: 631/378/1686; 631/378/2619/1533; Administration, Topical; Animals; Brain stem; Cochlea; Confocal microscopy; Correction of Hearing Impairment - methods; Disease Models, Animal; Hearing loss; Hearing Loss, Sensorineural - therapy; Hearing protection; Humanities and Social Sciences; Mice; multidisciplinary; Neurotrophic factors; Neurotrophin 3; Neurotrophin 3 - administration & dosage; Recovery of function; Regeneration; Science; Sensory neurons; Synapses; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep24907

In acquired sensorineural hearing loss, such as that produced by noise or aging, there can be massive loss of the synaptic connections between cochlear sensory cells and primary sensory neurons, without loss of the sensory cells themselves. Because the cell bodies and central projections of these cochlear neurons survive for months to years, there is a long therapeutic window in which to re-establish functional connections and improve hearing ability. Here we show in noise-exposed mice that local delivery of neurotrophin-3 (NT-3) to the round window niche, 24 hours after an exposure that causes an immediate loss of up to 50% loss of synapses in the cochlear basal region, can regenerate pre- and post-synaptic elements at the hair cell / cochlear nerve interface. This synaptic regeneration, as documented by confocal microscopy of immunostained cochlear sensory epithelia, was coupled with a corresponding functional recovery, as seen in the suprathreshold amplitude of auditory brainstem response Wave 1. Cochlear delivery of neurotrophins in humans is likely achievable as an office procedure via transtympanic injection, making our results highly significant in a translational context.