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Loss of cochlear nucleus neurons following aminoglycoside antibiotics or cochlear removal
D R Moore1, N J Rogers, S J O'Leary
1University Laboratory of Physiology, Oxford, England.
Abstract:
This study compared the effects of aminoglycoside ototoxicity and surgical ablation of the cochlea in infancy on the survival of neurons in the rat cochlear nucleus (CN). Ototoxicity was induced by a single, systemic dose of gentamicin sulfate and furosemide on postnatal day 6 (P6), P7, or P10, and assessed by the elevation of auditory brain stem response thresholds, as described in a companion paper. Unilateral cochlear removals were performed under Saffan anesthesia on P6, P9, and P12. Rats were painlessly sacrificed in adulthood, and the formalin-perfused brains and cochleas were embedded in wax, sectioned, and stained. Ototoxic treatment at P6 through P10 did not reduce neuron counts in the CN. Cochlear removal at P6 resulted in a 40% loss of CN neurons, but removal at P12 did not result in CN neuron loss. These data suggest that the critical period for the dependence of CN neurons on afferent input from the cochlea ends at the same time that susceptibility to aminoglycoside ototoxicity begins.
Insights
Aminoglycoside ototoxicity did not harm rat cochlear nucleus (CN) neurons. However, early cochlear removal (P6) caused significant neuron loss, suggesting a critical developmental period for auditory input.
Area of Science:
- Neuroscience
- Ototoxicology
- Developmental Biology
Background:
- Aminoglycoside antibiotics can cause hearing loss.
- The cochlear nucleus (CN) processes auditory information.
- Early life auditory input is crucial for neural development.
Purpose of the Study:
- To compare the effects of aminoglycoside ototoxicity and early cochlear removal on cochlear nucleus neuron survival in rats.
- To determine the critical period for cochlear input dependence in rat CN neurons.
Main Methods:
- Induced ototoxicity with gentamicin sulfate and furosemide at specific postnatal days (P6, P7, P10).
- Performed unilateral cochlear removals at P6, P9, and P12.
- Assessed auditory brain stem response thresholds and quantified CN neuron counts in adulthood.
Main Results:
- Ototoxic treatment from P6 to P10 did not reduce CN neuron counts.
- Cochlear removal at P6 resulted in a 40% loss of CN neurons.
- Cochlear removal at P12 did not lead to CN neuron loss.
Conclusions:
- Susceptibility to aminoglycoside ototoxicity begins after the critical period for CN neuron dependence on cochlear input.
- Early cochlear removal significantly impacts the development of the auditory pathway.