Morphological and functional alterations of the cochlea in apolipoprotein E gene deficient mice.
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.
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ABSTRACT: Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI.Cell Death & Disease 04/2014; 5:e1189. · 5.18 Impact Factor
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ABSTRACT: Objectives Published literature shows that individual nutrients could influence the risk of developing vision and hearing loss. There is, however, a lack of population-based data on the relationship between overall patterns of food intake and the presence of concurrent vision and hearing impairment. We aimed to assess the associations between diet quality with the prevalence and 5-year incidence of dual sensory impairment (DSI). Design Cross-sectional and 5-year longitudinal analyses. Setting Blue Mountains, Sydney, Australia. Participants 2443 participants aged ≥50 from baseline were examined and followed over 5 years. Measurements Dietary data were collected using a semi-quantitative food frequency questionnaire. A modified version of the Healthy Eating Index for Australians was developed to determine total diet score (TDS). Visual impairment was defined as visual acuity less than 20/40 (better eye), and hearing impairment as average puretone air conduction threshold greater than 25 dB HL (500–4000 Hz, better ear). Results After adjusting for age, sex, education, noise exposure, current smoking, and type 2 diabetes, participants in the lowest compared to the highest quintile of TDS had a 2-fold increased likelihood of having prevalent DSI, odds ratio, OR, 2.62 (95% confidence intervals, CI, 1.08–6.36), P-trend=0.04. Significant associations were not observed between TDS and the prevalence of having a single sensory impairment (vision or hearing loss). Baseline TDS was not significantly associated with the 5-year incidence of DSI. Adherence to dietary guidelines was associated with a reduced likelihood of having DSI in cross-sectional, but not in longitudinal analyses. Conclusions Further studies with adequate power are warranted to assess the prospective relationship between diet quality and DSI.The Journal of Nutrition Health and Aging 01/2014; · 2.66 Impact Factor
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ABSTRACT: Niemann-Pick disease, type C1 (NPC1) is a rare lysosomal lipidosis that is most often the result of biallelic mutations in NPC1, and is characterized by a fatal neurological degeneration. The pathophysiology is complex, and the natural history of the disease is poorly understood. Recent findings from patients with NPC1 and hearing loss suggest that multiple steps along the auditory pathway are affected. The current study was undertaken to determine the auditory phenotype in the Npc1 (nih) mutant mouse model, to extend analyses to histologic evaluation of the inner ear, and to compare our findings to those reported from human patients. Auditory testing revealed a progressive high-frequency hearing loss in Npc1 (-/-) mice that is present as early as postnatal day 20 (P20), well before the onset of overt neurological symptoms, with evidence of abnormalities involving the cochlea, auditory nerve, and brainstem auditory centers. Distortion product otoacoustic emission amplitude and auditory brainstem response latency data provided evidence for a disruption in maturational development of the auditory system in Npc1 (-/-) mice. Anatomical study demonstrated accumulation of lysosomes in neurons, hair cells, and supporting cells of the inner ear in P30 Npc1 (-/-) mice, as well as increased numbers of inclusion bodies, myelin figures, and swollen nerve endings in older (P50-P70) mutant animals. These findings add unique perspective to the pathophysiology of NPC disease and suggest that hearing loss is an early and sensitive marker of disease progression.Journal of the Association for Research in Otolaryngology 05/2014; · 2.55 Impact Factor