title: Low Iron Diet Increases Susceptibility to Noise-Induced Hearing Loss in Young Rats.
abstract: We evaluated the role of iron deficiency (ID) without anemia on hearing function and cochlear pathophysiology of young rats before and after noise exposure. We used rats at developmental stages as an animal model to induce ID without anemia by dietary iron restriction. We have established this dietary restriction model in the rat that should enable us to study the effects of iron deficiency in the absence of severe anemia on hearing and ribbon synapses. Hearing function was measured on Postnatal Day (PND) 21 after induction of ID using auditory brainstem response (ABR). Then, the young rats were exposed to loud noise on PND 21. After noise exposure, hearing function was again measured. We observed the morphology of ribbon synapses, hair cells and spiral ganglion cells (SGCs), and assessed the expression of myosin VIIa, vesicular glutamate transporter 3 and prestin in the cochlea. ID without anemia did not elevate ABR threshold shifts, but reduced ABR wave I peak amplitude of young rats. At 70, 80, and 90 dB SPL, amplitudes of wave I (3.11 ± 0.96 µV, 3.52 ± 1.31 µV, and 4.37 ± 1.08 µV, respectively) in pups from the ID group were decreased compared to the control (5.92 ± 1.67 µV, 6.53 ± 1.70 µV, and 6.90 ± 1.76 µV, respectively) (p < 0.05). Moreover, ID without anemia did not impair the morphology hair cells and SGCs, but decreased the number of ribbon synapses. Before noise exposure, the mean number of ribbon synapses per inner hair cell (IHC) was significantly lower in the ID group (8.44 ± 1.21) compared to that seen in the control (13.08 ± 1.36) (p < 0.05). In addition, the numbers of ribbon synapses per IHC of young rats in the control (ID group) were 6.61 ± 1.59, 3.07 ± 0.83, 5.85 ± 1.63 and 12.25 ± 1.97 (3.75 ± 1.45, 2.03 ± 1.08, 3.81 ± 1.70 and 4.01 ± 1.65) at 1, 4, 7 and 14 days after noise exposure, respectively. Moreover, ABR thresholds at 4 and 8 kHz in young rats from the ID group were significantly elevated at 7 and 14 days after noise exposure compared to control (p < 0.05). The average number of young rat SGCs from the ID group were significantly decreased in the basal turn of the cochlea compared to the control (p < 0.05). Therefore, ID without anemia delayed the recovery from noise-induced hearing loss and ribbon synapses damage, increased SGCs loss, and upregulated prestin after noise exposure. Thus, the cochleae in rat pups with ID without anemia were potentially susceptible to loud noise exposure, and this deficit may be attributed to the reduction of ribbon synapses and SGCs.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China. yufei@mail.cmu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang 110001, China. kellya@163.com.
authors.forename: Shuai
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Otolaryngology, First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang 110001, China. feigo_dl@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China. ford_cmu@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China. yangjun@mail.cmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D001309:Auditory Threshold / Q000528:radiation effects; D001933:Brain Stem / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D003051:Cochlea / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D003056:Cochlear Nerve / Q000378:metabolism / Q000503:physiopathology* / Q000528:radiation effects / Q000648:ultrastructure; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D006317:Hearing Loss, Noise-Induced / Q000209:etiology* / Q000517:prevention & control; D019266:Iron, Dietary / Q000627:therapeutic use; D008297:Male; D008855:Microscopy, Electron, Scanning; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009622:Noise / Q000009:adverse effects; D009752:Nutritional Status; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013136:Spiral Ganglion / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D014886:Weaning
chemical_list: D019266:Iron, Dietary; D009419:Nerve Tissue Proteins
keywords: iron deficiency without anemia; ribbon synapse; spiral ganglion cell