Hassler, Brenda (2025) Study of Molecular Mechanisms of Age-Related Hearing Loss and in Impact of Hearing Aids on Cognitive Decline in Aging. [Tesi di dottorato]

Documento PDF PhD_Thesis_Brenda_Hassler.pdf Download (2MB)

Abstract

Hearing loss represents one of the most prevalent sensory impairments worldwide and is a major determinant of reduced quality of life in older adults. Among its various forms, age-related hearing loss (ARHL) is particularly clinically relevant due to its strong association with social isolation, cognitive decline, and neurodegeneration. Despite its clinical relevance, the molecular mechanisms underlying ARHL remain only partially understood. This thesis explores oxidative and inflammatory processes contributing to cochlear and neural degeneration using complementary experimental models of ototoxicity (cisplatin and styrene exposure) and physiological aging in C57BL/6 mice, together with a clinical study assessing cognitive and emotional outcomes in elderly patients following hearing aid rehabilitation. In experimental rat model, cisplatin administration caused dose-dependent auditory threshold elevation, degeneration of spiral ganglion neurons (SGNs) and afferent fibers, and reduced activation of the TrkB/AKT neurotrophic pathway, accompanied by increased p75NTR and cleaved caspase-3 expression. Styrene exposure induced marked oxidative stress and NLRP3 inflammasome activation, leading to elevated IL-1β and NF-κB signaling. Both the antioxidant rosmarinic acid and the anti- inflammatory anakinra attenuated cochlear injury, with anakinra providing earlier and stronger functional protection. In C57BL/6 mice, progressive high-frequency hearing loss at six months was associated with SGN loss and increased cochlear oxidative and inflammatory markers, indicating convergence of redox and immune mechanisms during auditory aging. A clinical study on elderly new hearing-aid users (aged 60–75 years) showed modest improvements in cognitive performance (MMSE, MoCA) and reduced anxiety (HADS-A) after three months, suggesting short-term cognitive and emotional benefits of hearing rehabilitation. Collectively, these results identify oxidative stress and inflammatory signaling as convergent drivers of cochlear degeneration. Interventions that restore redox and suppress inflammasome activation, combined with auditory rehabilitation, may provide a multifaceted approach to counteracting age-related hearing decline and its neurological consequences.

Downloads

Actions (login required)

Modifica documento