Research Article: Besides Huntington’s disease, does brain-type creatine kinase play a role in other forms of hearing impairment resulting from a common pathological cause?

Date Published: June 15, 2011

Publisher: Impact Journals LLC

Author(s): Yow-Sien Lin, Chih-Hung Wang, Yijuang Chern.



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). 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. 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. 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 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. Because creatine is an antioxidant, we postulated that creatine might enhance expression of CKB by reducing oxidative stress. 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. Most importantly, dietary supplements may be beneficial to patients with these hearing deficiencies.

Partial Text

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder with onset usually in middle age. Clinical features of HD include uncontrollable motor movements, cognitive impairment, and psychiatric symptoms [1]. 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. In addition to altered functions in the central nervous system, the expression of mutant Htt was also found in peripheral tissues [2-4], and was directly linked to local tissue defects [5, 6]. We recently reported that patients and mice with HD have hearing impairment [7], for which an association between dysregulated brain-type creatine kinase (CKB) and impaired hearing in HD mice was demonstrated. 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. 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) [7]. It would be of great interest in the future to evaluate whether hearing loss of HD patients can be treated by dietary creatine supplements.





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