Nrf2 deficiency enhances oxidative stress and promotes susceptibility to tinnitus in mice
Abstract Tinnitus is a prevalent and distressing medical symptom, and no effective pharmacological treatment currently exists. Despite significant advances, tinnitus remains a scientific enigma. To explore the molecular underpinnings of tinnitus, we developed a noise-induced tinnitus model in mice a...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-01509-x |
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| Summary: | Abstract Tinnitus is a prevalent and distressing medical symptom, and no effective pharmacological treatment currently exists. Despite significant advances, tinnitus remains a scientific enigma. To explore the molecular underpinnings of tinnitus, we developed a noise-induced tinnitus model in mice and utilized metabolomics to identify key differences in metabolic pathways. Our results revealed that oxidative stress-related pathways, including glutathione (GSH) metabolism, were significantly enriched in the auditory cortex of mice exhibiting tinnitus-like behavior. To further explore the role of oxidative stress, we examined the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) in tinnitus by conducting experiments in Nrf2 knockout (Nrf2-KO) mice. While Nrf2-deficient mice did not develop spontaneous tinnitus or hearing loss, they displayed increased susceptibility to prolonged tinnitus-like behavior after noise exposure. This was accompanied by heightened microglial activation, neuroinflammation, and significant alterations in gut microbiota composition, including greater diversity and dysbiosis. Our findings highlight a novel mechanism underlying tinnitus, emphasizing the role of oxidative stress in the auditory cortex and its connection to noise-induced tinnitus. The deficiency of Nrf2 in mice increases their susceptibility to tinnitus, suggesting that Nrf2 may serve as a promising therapeutic target for preventing noise-induced tinnitus. |
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| ISSN: | 2045-2322 |