Related Experiment Video
Updated: May 5, 2026
Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function
Published on: January 22, 2017
Dysregulated brain creatine kinase is associated with hearing impairment in mouse models of Huntington disease
Yow-Sien Lin1, Chiung-Mei Chen, Bing-wen Soong
1Molecular Medicine Program, National Yang-Ming University, Taipei, Taiwan.
Insights
Huntington disease (HD) is linked to hearing loss, affecting auditory processing. Creatine supplements may help treat these hearing abnormalities in HD patients.
Area of Science:
- Neuroscience
- Genetics
- Auditory Science
Background:
- Huntington disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene (HTT).
- Peripheral auditory function in HD patients remains under-assessed, despite known auditory processing deficits in late-stage disease.
Purpose of the Study:
- To comprehensively assess peripheral auditory function in Huntington disease patients.
- To investigate the underlying mechanisms of hearing impairment in HD.
- To explore potential therapeutic interventions for auditory dysfunction in HD.
Main Methods:
- Pure-tone audiometry and auditory brainstem response (ABR) assessments in 19 HD patients.
- Auditory brainstem response (ABR) testing in two mouse models of HD.
- Immunohistochemistry, quantitative RT-PCR, and Western blot analyses in HD mouse models.
Main Results:
- HD patients exhibited significantly elevated pure-tone audiometry thresholds, indicating hearing impairment.
- Elevated ABR thresholds were observed in both HD patients and HD mouse models.
- Mutant huntingtin was found in the organ of Corti in HD mice, and cochlear expression of brain creatine kinase (CKB) was reduced.
- Creatine supplementation ameliorated hearing impairment in HD mice.
Conclusions:
- Hearing loss is an authentic symptom of Huntington disease.
- Impaired phosphocreatine-creatine kinase (PCr-CK) system in the cochlea may contribute to HD-related hearing impairment.
- Creatine shows potential as a therapeutic agent for auditory abnormalities in Huntington disease.
Abstract:
Huntington disease (HD) is a degenerative disorder caused by expanded CAG repeats in exon 1 of the huntingtin gene (HTT). Patients with late-stage HD are known to have abnormal auditory processing, but the peripheral auditory functions of HD patients have yet to be thoroughly assessed. In this study, 19 HD patients (aged 40-59 years) were assessed for hearing impairment using pure-tone audiometry and assessment of auditory brainstem responses (ABRs). PTA thresholds were markedly elevated in HD patients. Consistent with this, elevated ABR thresholds were also detected in two mouse models of HD. Hearing loss thus appears to be an authentic symptom of HD. Immunohistochemical analyses demonstrated the presence of mutant huntingtin that formed intranuclear inclusions in the organ of Corti of HD mice, which might interfere with normal auditory function. Quantitative RT-PCR and Western blot analyses further revealed reduced expression of brain creatine kinase (CKB), a major enzyme responsible for ATP regeneration via the phosphocreatine-creatine kinase (PCr-CK) system, in the cochlea of HD mice. Treatment with creatine supplements ameliorated the hearing impairment of HD mice, suggesting that the impaired PCr-CK system in the cochlea of HD mice may contribute to their hearing impairment. These data also suggest that creatine may be useful for treating the hearing abnormalities of patients with HD.
