![]() ![]() It would be of great interest in the future to evaluate whether hearing loss of HD patients can be treated by dietary creatine supplements.įigure 1. Interestingly, dietary creatine supplements to HD mice not only rescued the expression of cochlear CKB but also restored the hearing of HD mice (Figure 1). Expression levels of CKB in the cochlea of two different HD mice models (R6/2 and Hdh (CAG)150) were significantly lower than that of WT mice, suggesting that the impairment of CKB in the cochlea is likely an authentic defect of HD. We recently reported that patients and mice with HD have hearing impairment, for which an association between dysregulated brain-type creatine kinase (CKB) and impaired hearing in HD mice was demonstrated. In addition to altered functions in the central nervous system, the expression of mutant Htt was also found in peripheral tissues, and was directly linked to local tissue defects. Although the causative gene (Huntingtin, HTT) of HD is ubiquitously expressed, the polyglutamine (polyQ)-expanded mutant Huntingtin protein (Htt) forms nuclear and neutrophil aggregates and preferentially affects the striatum and cerebral cortex. Clinical features of HD include uncontrollable motor movements, cognitive impairment, and psychiatric symptoms. Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder with onset usually in middle age. Most importantly, dietary supplements may be beneficial to patients with these hearing deficiencies. ![]() In addition to HD-related hearing impairment, inferior CKB expression and/or an impaired PCr-CK system may also play an important role in other hearing impairments caused by elevated levels of ROS. Because creatine is an antioxidant, we postulated that creatine might enhance expression of CKB by reducing oxidative stress. We also showed that dietary creatine supplementation rescued the impaired PCr-CK system and improved the expression of cochlear brain-type creatine kinase (CKB) in HD mice, thereby restoring their hearing. Given the importance of noninvasive biomarkers and the easy access of hearing tests, the symptom of hearing loss in HD patients may serve as a useful clinical indicator of disease onset and progression of HD. We recently showed that patients and mice with Huntington's disease (HD) have hearing impairment and that the dysregulated phosphocreatine (PCr)-creatine kinase (CK) system may account for this auditory dysfunction. Cochleae are more vulnerable to oxidative stress than other organs because of the high metabolic demands of their mechanosensory hair cells in response to sound stimulation. Hearing impairment following cochlear damage due to noise trauma, ototoxicity caused by aminoglycoside antibiotics, or age-related cochlear degeneration was linked to a common pathogenesis involving the formation of reactive oxygen species (ROS). ![]()
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