Otoprotective Effects Of Ethosuximide In NOD/LtJ Mice With Early-Onset Age-Related Hearing Loss

Hypothesis:Treatment with ethosuximide medications could decrease the cochlear cells degeneration and protect presbycusis in NOD/LtJ mouse.Background:Despite long time efforts to study the mechanism of presbycusis, the researchers did not find any therapies to cure it. Apoptotic cell death, including hair cells and spiral ganglion neurons (SGNs) in the cochlea was proposed to be the classic theory to presbycusis. As we all know that calcium signaling play key roles in signal transduction in apoptosis, we selected ethosuximide to inhibit the apoptosis pathway and the primary mechanism to treat relates to blocking T-type calcium channels and suppressing Ca2+ion.Methods:Animals were divided into ethosuximide-treated group and untreated group. Auditory function, morphometric analysis and related genes variations were monitored in this study.Results:Auditory brainstem response (ABR) and distortion product oto-acoustic emission (DPOAE) testing revealed early-onset, rapid progressive hearing loss in NOD/LtJ mice. Histological examination displayed progressive cochlear cells loss that follows hearing loss. The ethosuximide-treated group showed more cochlear cells survival and better auditory function than the untreated group.Conclusion:Ethosuximide had significant effect on protecting hearing in NOD/LtJ mice and preventing cochlear cells degeneration, simultaneously, it could down regulate gene expression in the apoptosis pathways. The molecular mechanisms underlying presbycusis were unknown, but our findings suggested that the inhibition of T-type calcium channel and downstream genes might be a key mechanism of presbycusis in NOD/LtJ mice.