Document Detail

Dysregulated brain creatine kinase is associated with hearing impairment in mouse models of Huntington disease.
MedLine Citation:
PMID:  21403395     Owner:  NLM     Status:  MEDLINE    
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.
Yow-Sien Lin; Chiung-Mei Chen; Bing-wen Soong; Yih-Ru Wu; Hui-Mei Chen; Wen-Ying Yeh; Dai-Rong Wu; Yi-Jun Lin; Paul Wai-Fung Poon; Mei-Ling Cheng; Chih-Hung Wang; Yijuang Chern
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-14
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  121     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-14     Completed Date:  2011-06-21     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1519-23     Citation Subset:  AIM; IM    
Molecular Medicine Program, National Yang-Ming University, Taipei, Taiwan.
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MeSH Terms
Audiometry, Pure-Tone
Blotting, Western
Case-Control Studies
Cochlea / drug effects,  enzymology
Creatine / pharmacology
Creatine Kinase, BB Form / genetics*
Disease Models, Animal
Evoked Potentials, Auditory, Brain Stem
Gene Expression
Hearing Loss / drug therapy,  enzymology*,  etiology,  genetics*
Huntington Disease / complications,  enzymology*,  genetics*,  physiopathology
Mice, Transgenic
Middle Aged
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
57-00-1/Creatine; EC Kinase, BB Form

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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