Hearing Loss and Cochlear Pathology in a Type II Diabetic Mouse Model

Abstract

Objective: 1) Determine whether a type II diabetic mouse model demonstrates hearing loss. 2) Examine cochlear ultrastructure of a type II diabetic mouse model for evidence of pathology. Method: The Leprdb/Leprdb (db/db) mouse has a leptin receptor point mutation which manifests as polyphagia, hyperglycemia, and obesity, mimicking type II diabetes. Db/db and wild type mice from the parent strain underwent auditory brainstem response measurements followed by cochlear ultrastructure analysis using scanning and transmission electron microscopy. Results: At 12 weeks of age, the mutant animals demonstrate a profound hearing loss from 8 to 32 kHz, which is in contrast to published data of a 10 dB shift at 8 kHz and 30 dB shift at 16 to 32 kHz for age-matched, wild type C57BL/6J counterparts. In addition, fine structure analysis reveals evidence of morphological alterations in multiple locations within the cochlea, including loss of neuron density in the spiral ganglion, stria vascularis edema, and endothelial abnormalities within strial capillaries. Agematched controls are without similar ultrastructural changes. Scanning electron microscopy reveals no evidence of hair cell loss or other identifiable abnormalities. Conclusion: This is the first demonstration of cochlear pathophysiology in a genetically derived type II diabetic mouse model. Use of the db/db mouse provides an opportunity to investigate the underlying mechanism of type II diabetes associated hearing loss.