L-Ergothioneine slows the progression of age-related hearing loss in CBA/CaJ mice

Mark A Bauer; Parveen Bazard; Alejandro A Acosta; Nidhi Bangalore; Lina Elessaway; Mark Thivierge; Moksheta Chellani; Xiaoxia Zhu; Bo Ding; Joseph P Walton; Robert D Frisina

doi:10.1016/j.heares.2024.109004

L-Ergothioneine slows the progression of age-related hearing loss in CBA/CaJ mice

Hear Res. 2024 May:446:109004. doi: 10.1016/j.heares.2024.109004. Epub 2024 Apr 2.

Authors

Affiliations

¹ Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA.
² Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA. Electronic address: parveen1@usf.edu.
³ School of Medicine, University of Puerto Rico, San Juan, 00925 Puerto Rico; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA.
⁴ Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA; Biomedical Sciences - Dept. of Chemistry, University of South Florida, Tampa, FL 33620, USA; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA.
⁵ Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA; Department Communication Sciences and Disorders, College of Behavioral & Community Sciences, Tampa, FL 33620, USA; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA.
⁶ Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL, 33620, USA; Department Communication Sciences and Disorders, College of Behavioral & Community Sciences, Tampa, FL 33620, USA; Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA. Electronic address: rfrisina@usf.edu.

PMID: 38608332
DOI: 10.1016/j.heares.2024.109004

Abstract

The naturally occurring amino acid, l-ergothioneine (EGT), has immense potential as a therapeutic, having shown promise in the treatment of other disease models, including neurological disorders. EGT is naturally uptaken into cells via its specific receptor, OCTN1, to be utilized by cells as an antioxidant and anti-inflammatory. In our current study, EGT was administered over a period of 6 months to 25-26-month-old CBA/CaJ mice as a possible treatment for age-related hearing loss (ARHL), since presbycusis has been linked to higher levels of cochlear oxidative stress, apoptosis, and chronic inflammation. Results from the current study indicate that EGT can prevent aging declines of some key features of ARHL. However, we found a distinct sex difference for the response to the treatments, for hearing - Auditory Brainstem Responses (ABRs) and Distortion Product Otoacoustic Emissions (DPOAEs). Males exhibited lower threshold declines in both low dose (LD) and high dose (HD) test groups throughout the testing period and did not display some of the characteristic aging declines in hearing seen in Control animals. In contrast, female mice did not show any therapeutic effects with either treatment dose. Further confirming this sex difference, EGT levels in whole blood sampling throughout the testing period showed greater uptake of EGT in males compared to females. Additionally, RT-PCR results from three tissue types of the inner ear confirmed EGT activity in the cochlea in both males and females. Males and females exhibited significant differences in biomarkers related to apoptosis (Cas-3), inflammation (TNF-a), oxidative stress (SOD2), and mitochondrial health (PGC1a).These changes were more prominent in males as compared to females, especially in stria vascularis tissue. Taken together, these findings suggest that EGT has the potential to be a naturally derived therapeutic for slowing down the progression of ARHL, and possibly other neurodegenerative diseases. EGT, while effective in the treatment of some features of presbycusis in aging males, could also be modified into a general prophylaxis for other age-related disorders where treatment protocols would include eating a larger proportion of EGT-rich foods or supplements. Lastly, the sex difference discovered here, needs further investigation to see if therapeutic conditions can be developed where aging females show better responsiveness to EGT.

Keywords: Age-related hearing loss; Auditory brainstem responses (ABRs); Distortion product otoacoustic emissions (DPOAEs); Ergothioneine; Mice; Reverse transcriptase polymerase chain reaction (RT-PCR); Sex selectivity.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Aging* / drug effects
Aging* / pathology
Animals
Anti-Inflammatory Agents / pharmacology
Antioxidants* / pharmacology
Apoptosis / drug effects
Auditory Threshold / drug effects
Cochlea* / drug effects
Cochlea* / metabolism
Cochlea* / pathology
Cochlea* / physiopathology
Disease Models, Animal*
Disease Progression*
Ergothioneine* / pharmacology
Evoked Potentials, Auditory, Brain Stem* / drug effects
Female
Hearing / drug effects
Male
Mice
Mice, Inbred CBA*
Otoacoustic Emissions, Spontaneous / drug effects
Oxidative Stress* / drug effects
Presbycusis* / drug therapy
Presbycusis* / metabolism
Presbycusis* / pathology
Presbycusis* / physiopathology
Presbycusis* / prevention & control
Sex Factors
Superoxide Dismutase / metabolism

Substances

Ergothioneine
Antioxidants
Superoxide Dismutase
Anti-Inflammatory Agents