Supplement: ATP-Purinergic Mechanisms Underlying Noise-Induced Cochlear Synaptopathy and Hearing Loss

  • Zhao, Hong-Bo (PI)

Grants and Contracts Details


Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive loss of memory and cognitive decline. Hearing is an important neuralsensory stimulation and input for central neural system and cognition. Previous studies demonstrated that hearing loss is associated with dementia (Shahmiri et al., 2017; Swords et al., 2018; Thomson et al., 2017; Tuwaig et al., 2017). Both peripheral and central auditory system dysfunctions occur in the prodromal stages of AD, and therefore may represent early indicators of the disease. Noise exposure known to damage the cochlea can lead to more general cognitive dysfunction (Cernak et al., 2001; Zheng et al., 2011a&b). Recent studies further demonstrated that noise can induce irreversible degeneration of synapses between inner hair cells (IHCs) and auditory nerves (AN) leading to hidden hearing loss (HHL), which can eventually induce difficulty hearing and understanding (Plack et al., 2014; Liberman and Kujawa, 2017; Pienkowski, 2017). Our primary goals in the parent R01 are to investigate HHL mechanisms and the role of ATP-purinergic signaling in the noise-induced cochlear synaptopathy and hearing loss. The proposed studies are going well. The new data also revealed that HHL and agerelated hearing loss may share the same mechanism and that ATP-purinergic signaling may also have a critical role in age-related hearing loss. Age-related hearing loss is a high-risk factor for AD dementia (Loughrey et al., 2018). In this supplement, we intend to further investigate the possible link between the HHL and AD dementia development and the role of ATP-purinergic signaling in AD dementia generation. Since hearing loss could be a biomarker of pre-clinical AD observed 5 to 10 years prior to an official AD diagnoses (Iliadou et al., 2003; Bateman et al., 2012), the proposed additional studies may not only shed light on the mechanisms underlying AD dementia but also provide interesting data for early detecting and diagnosis of AD and dementia.
Effective start/end date3/22/186/30/21


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