Morphological and functional alterations of the cochlea in apolipoprotein E gene deficient mice.
The relationship between hyperlipidemia and sensorineural hearing loss remains obscure. In this study, we elucidate for the first time the cochlear morphological and auditory alterations and their relationships with hyperlipidemia, atherosclerosis, and endothelial dysfunction in apolipoprotein-E knockout (ApoE-KO) mice. Ten-week-old ApoE-KO mice were fed either atherosclerotic diet (1.25% cholesterol) or normal diet. Wild type mice (C57BL/6J) served as normal controls. Fourteen weeks later, marked hyperlipidemia, atherosclerosis, endothelial dysfunction, and hearing impairment, especially in the high frequencies, had developed in ApoE-KO mice as compared with C57BL/6J mice (P<0.001). A high positive correlation between hearing loss and the extent of atherosclerosis and plasma total cholesterol levels was found. Hearing loss, especially at high frequencies, was detected in all ApoE-KO mice. Hair cell loss mainly at the base turn, thickening of vascular intima, and lumen stenosis of the spiral modiolar artery (SMA) in cochlea were also found; these histological changes were exacerbated by the atherosclerotic diet. Furthermore, endothelial nitric oxide synthase (eNOS) in aortic wall and cochlea was distinctly reduced in ApoE-KO mice. These results demonstrate that hyperlipidemia and atherosclerosis can induce alterations in cochlear morphology and function. The stenosis of SMA, which may cause cochlear ischemia and hypoxia, endothelial dysfunction, and low eNOS activity, may contribute to hearing loss.
Guo
Yunkai
Y
Division of Allergy and Immunology, Departments of Medicine, Molecular Sciences and Otolaryngology and Neuroscience Institute, College of Medicine, VA Medical Center, Memphis, TN 38104, USA.
Zhang
Chunxiang
C
Du
Xiaoping
X
Nair
Usha
U
Yoo
Tai-June
TJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics; D001309:Auditory Threshold; D002784:Cholesterol / Q000097:blood; D003051:Cochlea / Q000473:pathology* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006198:Hair Cells, Auditory / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006949:Hyperlipidemias / Q000150:complications / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009925:Organ of Corti / Q000098:blood supply / Q000473:pathology; D014664:Vasodilation / Q000187:drug effects
D001057:Apolipoproteins E; D002784:Cholesterol; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000109:Acetylcholine