Jessica Newman
Pronouns: she/her
Research Mentor(s): Gabriel Corfas
Research Mentor School/College/Department: Kesge Hearing Research Institute / Medicine
Program: UROP
Session: Session 2 (10:00am – 10:50am)
Authors: Jessica Newman, Luis Cassinotti, Gabriel Corfas
Abstract
Age-related hearing loss (ARHL) is the most common sensory deficit in the elderly, affecting one third of adults over 65, and half of adults over age 85. An early event in ARHL is thought to be IHC synaptopathy, defined as the loss of synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs). In mice, IHC synaptopathy can be measured by a decrease in Auditory Brainstem Response (ABR) Peak 1 Amplitudes, or by directly counting synapses via histology. Recently we demonstrated that age-related IHC synaptopathy can be delayed by overexpression of neurotrophin-3 (Ntf3) starting at middle age in mice (Cassinotti et al., 2022). Interestingly, sound-driven auditory activity (measured as the amplitude of the first peak of the auditory brain stem response wave form (ABR Peak 1 amplitude)) increases 1 week after Ntf3 over-expression, suggesting the this neurotrophic factor enhances aspects of cochlear function. However, it remains unclear if the rapid increase in ABR Peak 1 amplitude is due to the formation of new synapses, the potentiation of the existing synapses, a combination of both factors, or through other mechanisms. We aim to determine how Ntf3 influences the function and structure of the middle-aged murine inner ear. First, we were successful in reproducing the acute effects of Ntf3 over-expression on sound-driven auditory signaling (increases in ABR peak 1 amplitudes seen 1-week after Ntf3 overexpression). Then, cochleae were collected from the mice to determine the effects of Ntf3 on IHC-SGN synapse density by immunofluorescence and confocal microscopy. Another set of cochlea will be used to determine the impact of Ntf3 over-expression on gene expression using bulk mRNA sequencing. This experiments are ongoing. References: Cassinotti, L. R., Ji, L., Borges, B. C., Cass, N. D., Desai, A. S., Kohrman, D. C., Liberman, M. C., & Corfas, G. (2022). Cochlear Neurotrophin-3 overexpression at mid-life prevents age-related inner hair cell synaptopathy and slows age-related hearing loss. Aging Cell, 00, e13708. https://doi.org/10.1111/acel.13708, Aging Cell, (2022).
