Author's personal copy Anti-epileptic drugs delay age-related loss of spiral ganglion neurons via T-type calcium channel

Abstract

a b s t r a c t Loss of spiral ganglion neurons is a major cause of age-related hearing loss (presbycusis). Despite being the third most prevalent condition afflicting elderly persons, there are no known medications to prevent presbycusis. Because calcium signaling has long been implicated in age-related neuronal death, we investigated T-type calcium channels. This family is comprised of three members (Ca v 3.1, Ca v 3.2, and Ca v 3.3), based on their respective main pore-forming alpha subunits: a1G, a1H, and a1I. In the present study, we report a significant delay of age-related loss of cochlear function and preservation of spiral ganglion neurons in a1H null and heterozygous mice, clearly demonstrating an important role for Ca v 3.2 in age-related neuronal loss. Furthermore, we show that anticonvulsant drugs from a family of T-type calcium channel blockers can significantly preserve spiral ganglion neurons during aging. To our knowledge, this is the first report of drugs capable of diminishing age-related loss of spiral ganglion neurons