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Review
. 2023 Jan 31;12(2):332.
doi: 10.3390/antiox12020332.

Redox Imbalance as a Common Pathogenic Factor Linking Hearing Loss and Cognitive Decline

Fabiola Paciello  1   2 , Cristian Ripoli  1   2 , Anna Rita Fetoni  3 , Claudio Grassi  1   2
Affiliations
Review

Redox Imbalance as a Common Pathogenic Factor Linking Hearing Loss and Cognitive Decline

Fabiola Paciello et al. Antioxidants (Basel). .

Abstract

Experimental and clinical data suggest a tight link between hearing and cognitive functions under both physiological and pathological conditions. Indeed, hearing perception requires high-level cognitive processes, and its alterations have been considered a risk factor for cognitive decline. Thus, identifying common pathogenic determinants of hearing loss and neurodegenerative disease is challenging. Here, we focused on redox status imbalance as a possible common pathological mechanism linking hearing and cognitive dysfunctions. Oxidative stress plays a critical role in cochlear damage occurring during aging, as well as in that induced by exogenous factors, including noise. At the same time, increased oxidative stress in medio-temporal brain regions, including the hippocampus, is a hallmark of neurodegenerative disorders like Alzheimer's disease. As such, antioxidant therapy seems to be a promising approach to prevent and/or counteract both sensory and cognitive neurodegeneration. Here, we review experimental evidence suggesting that redox imbalance is a key pathogenetic factor underlying the association between sensorineural hearing loss and neurodegenerative diseases. A greater understanding of the pathophysiological mechanisms shared by these two diseased conditions will hopefully provide relevant information to develop innovative and effective therapeutic strategies.

Keywords: antioxidant therapy; hearing loss; neurodegenerative disease; oxidative stress.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Ascending and descending auditory pathways.
Figure 2
Figure 2
Mechanisms of oxidative stress in the cochlea. (A): Schematic representation of cochlear anatomy, with the organ of Corti, containing one row of inner hair cells (IHC) and three rows of outer hair cells (OHC), the main structure involved in oxidative stress attack. SV: Scala Vestibuli; SM: Scala Media; ST: Scala Tympani; SGNs: Spiral Ganglion neurons. (B): Noise or aging insults can induce oxidative damage leading to cytochrome c release from the mitochondria, which activates the caspase apoptotic pathway. ROS overload causes in parallel an imbalance of endogenous antioxidant enzymes [Nrf-2, heme oxygenase-1 (HO-1), superoxide dismutases (SODs)] and an increase of pro-inflammatory markers (NF-κB, TNF-α, IL-1β) that contributes to pro-apoptotic pathway activation, leading to cell death. Finally, ROS leads to increased lipid peroxidation, affecting plasma membrane fluidity.
Figure 3
Figure 3
Mechanisms of oxidative stress in the brain. (A): Schematic representation of all damaging molecular mechanisms involved in ROS-mediated insult in neurodegenerative diseases. (B): Oxidative stress causes mitochondrial damage and ROS release, damaging neurons and leading to neuronal dysfunctions and cognitive decline by: (1) inducing microglia activation leading to neuroinflammation; (2) impairing ATP release, leading to caspase-dependent apoptotic pathways; (3) increasing neurofibrillary tangles (NFTs) accumulation caused by hyperphosphorylation of tau thought decreased PP2A activity and increased GSK3β; (4) facilitating misfolding protein aggregation as Ab accumulation.
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