title: Insulin resistance due to dietary iron overload disrupts inner hair cell ribbon synapse plasticity in male mice.
abstract: To evaluate whether cochlear inner hair cells (IHCs) ribbon synapse plasticity would be interrupted by insulin resistance (IR) due to dietary iron overload, we established an IR model in C57Bl/6 male mice with an iron-enriched diet for 16 weeks. Glucose levels were measured at weeks 4, 8, 12, 16. Glucose tolerance test and insulin tolerance test were performed at week 16 after overnight fasting. Then, auditory brainstem responses (ABRs) measurements were performed for hearing threshold shifts. After ABR measurements, cochleae were harvested for assessment of the number of IHC ribbon synapses by immunostaining, the morphology of cochlear hair cells and spiral ganglion neurons (SGNs) by transmission electron microscopy or immunostaining. Here, we show that IR due to dietary iron overload decreased the number of ribbon synapses, and induced moderate ABR threshold elevations. Besides, additional components including outer hair cells (OHCs), IHCs, and SGNs were unaffected. Moreover, IR did not disrupt the expression of vesicular glutamate transporter 3 (VGLUT3), myosin VIIa and prestin in hair cells. These results indicate that IHC ribbon synapses may be more susceptible to IR due to dietary iron overload.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang 110122, China. Electronic address: 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, Shenyang, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Otolaryngology, First Affiliated Hospital of China Medical University, Shenyang, China.
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 110122, China.
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 110122, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang 110122, China.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang 110122, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, China Medical University, China. Electronic address: chenjie@mail.cmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism; D000818:Animals; D016057:Evoked Potentials, Auditory, Brain Stem; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D007333:Insulin Resistance; D019190:Iron Overload / Q000378:metabolism* / Q000503:physiopathology; D019266:Iron, Dietary / Q000008:administration & dosage*; D008297:Male; D008810:Mice, Inbred C57BL; D020409:Molecular Motor Proteins / Q000378:metabolism; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism; D009473:Neuronal Plasticity; D013569:Synapses / Q000502:physiology*
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D019266:Iron, Dietary; D020409:Molecular Motor Proteins; D000081412:Myosin VIIa; D009218:Myosins; C000631456:Myo7a protein, mouse; C498720:Pres protein, mouse; C504941:Slc17a8 protein, mouse
keywords: Inner hair cell; Insulin resistance; Iron overload; Ribbon synapse