Publications (2)9.81 Total impact
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Article: Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss.
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ABSTRACT: Cochlear noise injury is the second most frequent cause of sensorineural hearing loss, after aging. Because calcium dysregulation is a widely recognized contributor to noise injury, we examined the potential of calcium channel blockers to reduce noise-induced hearing loss (NIHL) in mice. We focused on two T-type calcium blockers, trimethadione and ethosuximide, which are anti-epileptics approved by the Food and Drug Administration. Young C57BL/6 mice of either gender were divided into three groups: a 'prevention' group receiving the blocker via drinking water before noise exposure; a 'treatment' group receiving the blocker via drinking water after noise exposure; and controls receiving noise alone. Trimethadione significantly reduced NIHL when applied before noise exposure, as determined by auditory brainstem recording. Both ethosuximide and trimethadione were effective in reducing NIHL when applied after noise exposure. Results were influenced by gender, with males generally receiving greater benefit than females. Quantitation of hair cell and neuronal density suggested that preservation of outer hair cells could account for the observed protection. Immunocytochemistry and RT-PCR suggested that this protection involves direct action of T-type blockers on alpha1 subunits comprising one or more Ca(v)3 calcium channel types in the cochlea. Our findings provide a basis for clinical studies testing T-type calcium blockers both to prevent and treat NIHL.Hearing Research 05/2007; 226(1-2):52-60. · 2.70 Impact Factor -
Article: Requirement of nicotinic acetylcholine receptor subunit beta2 in the maintenance of spiral ganglion neurons during aging.
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ABSTRACT: Age-related hearing loss (presbycusis) is a major health concern for the elderly. Loss of spiral ganglion neurons (SGNs), the primary sensory relay of the auditory system, is associated consistently with presbycusis. The causative molecular events responsible for age-related loss of SGNs are unknown. Recent reports directly link age-related neuronal loss in cerebral cortex with the loss of high-affinity nicotine acetylcholine receptors (nAChRs). In cochlea, cholinergic synapses are made by olivocochlear efferent fibers on the outer hair cells that express alpha9 nAChR subunits and on the peripheral projections of SGNs that express alpha2, alpha4-7, and beta2-3 nAChR subunits. A significantly decreased expression of the beta2 nAChR subunit in SGNs was found specifically in mice susceptible to presbycusis. Furthermore, mice lacking the beta2 nAChR subunit (beta2-/-), but not mice lacking the alpha5 nAChR subunit (alpha5-/-), have dramatic hearing loss and significant reduction in the number of SGNs. Our findings clearly established a requirement for beta2 nAChR subunit in the maintenance of SGNs during aging.Journal of Neuroscience 04/2005; 25(12):3041-5. · 7.11 Impact Factor
