Morphological and functional alterations of the cochlea in apolipoprotein E gene deficient mice

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.
Hearing Research (Impact Factor: 2.85). 11/2005; 208(1-2):54-67. DOI: 10.1016/j.heares.2005.05.010
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sensorineural hearing loss (SNHL) is a major pathology of the inner ear that affects nearly 600 million people worldwide. Despite intensive researches, this major health problem remains without satisfactory solutions. The pathophysiological mechanisms involved in SNHL include oxidative stress, excitotoxicity, inflammation, and ischemia, resulting in synaptic loss, axonal degeneration, and apoptosis of spiral ganglion neurons. The mechanisms associated with SNHL are shared with other neurodegenerative disorders. Cholesterol homeostasis is central to numerous pathologies including neurodegenerative diseases and cholesterol regulates major processes involved in neurons survival and function. The role of cholesterol homeostasis in the physiopathology of inner ear is largely unexplored. In this review, we discuss the findings concerning cholesterol homeostasis in neurodegenerative diseases and whether it should be translated into potential therapeutic strategies for the treatment of SNHL.
    Frontiers in Aging Neuroscience 01/2015; 7:3. DOI:10.3389/fnagi.2015.00003 · 2.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The study is to establish a novel method to determine the endothelial function in mouse carotid arteries in vivo by using high-resolution ultrasound images. Atherosclerosis in carotid arteries is induced in ApoE(-/-) mice with a Western diet. The ultrasound of the ventral neck generates clear pictures of the common carotid arteries. Acetylcholine at the range from 5 to 20 μg/kg/min (iv) is able to induce a dose-dependent relaxation as shown by the increased diameter of these normal mouse carotid arteries, which is impaired in atherosclerotic arteries. The endothelial function determined by ultrasound images in vivo matches well with that determined in isolated carotid arterial rings in vitro. All animals survived after the endothelial function measurement. In this study, we have established a standard method to determine the mouse endothelial function in vivo. It is a reliable, safe, and survival method that could be used repetitively in mouse arteries.
    Journal of Cardiovascular Translational Research 02/2015; 8(2). DOI:10.1007/s12265-015-9614-8 · 2.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recently, epidemiological studies on the etiology of peripheral neuropathies have revealed that hyperlipidemia is a novel risk factor. Plasma lipid levels were confirmed to be associated with the incidence of many peripheral neuropathies including axonal distal polyneuropathy, vision and hearing loss, motor nerve system lesions and sympathetic nerve system dysfunction. Moreover, different lipid components such as cholesterol, triacylglycerols and lipoprotein are involved in the pathogenesis of these neuropathies. This review aimed to discuss the effect of hyperlipidemia on the peripheral nervous system and its association with peripheral neuropathies. Furthermore, a detailed discussion focusing on the explicit mechanisms related to hyperlipidemia-induced peripheral neuropathies is presented here. These mechanisms, including intracellular oxidative stress, inflammatory lesions, ischemia and dysregulation of local lipid metabolism, share pathways and interact mutually. In addition, we examined current information on clinical trials to prevent and treat peripheral neuropathies caused by hyperlipidemia, with a predictive discussion regarding the orientation of future investigations.
    Neural Regeneration Research 02/2012; 7(5):392-9. DOI:10.3969/j.issn.1673-5374.2012.05.011 · 0.23 Impact Factor