Project Name: "Inhibition of apoptosis as a means to mitigate hearing loss in mice"

Location: Northwestern University - Feinberg School of Medicine

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Alan M. Robinson, Ph.D.

Dr. Robinson is a Research Assistant Professor in the Department of Otolaryngology-Head and Neck Surgery. He conducted his Batchelor of Science Degree in biochemistry at the University of Bath, Avon, England. He received his M.S. and Ph.D. degrees in the biochemistry and molecular biology of steroid hormone regulated gene expression in breast cancer within the Ben May Institute for Cancer Research at the University of Chicago. He conducted post-doctoral research at Northwestern University in otology and olfaction and joined the faculty in 2000. He is currently shifting his focus from the olfactory system to hearing research within the department. Current studies involve prevention of cell death following aminoglycoside treatment in rodents and following noise exposure.

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"Inhibition of apoptosis as a means to mitigate hearing loss in mice"

Funded by the E.R. Capita Foundation

Initial studies were performed in Gerbil with the intention of moving into studies using mice, which are available with transgenic modification of apoptosis-related genes. The efficacy of the antibiotic minocycline as a therapeutic agent for amelioration of hearing loss in gerbils treated with the ototoxic aminoglycoside, neomycin was investigated. Minocycline is multifaceted in that it exhibits anti-inflammatory, antibiotic and anti-apoptotic properties in several neural and non-neural tissues. As an anti-apoptotic agent, minocycline would theoretically inhibit apoptosis of sensory cells within the inner ear when exposed to neomycin.
Baseline Auditory brainstem Responses (ABR) measurements were made on gerbils prior to experimental treatments. Gerbils then received a single trans-tympanic injection of 40mM neomycin in the left ear and Ringer’s balanced lactate in the right ear and either 0, 1.2 or 1.5 mg/kg intra-peritoneal injection of minocycline in normal saline daily for five days. Day 1 injection was given at commencement of the baseline ABR measurement.
Four weeks post-treatment ABR measurements were made and animals sacrificed for histological preparation of the cochleae. Analysis of pre and post treatment ABR measurements demonstrated minocycline amelioration of hearing loss. Quantification of spiral ganglion neurons is under way to determine if there is a correlation with the ABR measurements. Minocycline used in combination with other otoprotective agents is envisioned as a realistic means of preventing hearing loss due to aminoglycoside treatment. A manuscript is in preparation, which will detail the results of this work.
This study has lead on to investigation of changes in gene expression in the cochlea mediated by minocycline.

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