Anti-epileptic drugs delay age-related loss of spiral ganglion neurons via T-type calcium channel

• Published in: Hearing research 2011-08, Vol.278 (1), p.106-112
• Main Authors: Lei, Debin, Gao, Xia, Perez, Philip, Ohlemiller, Kevin K., Chen, Chien-Chang, Campbell, Kevin P., Hood, Aizhen Yang, Bao, Jianxin
• Format: Article
• Language: English
• Subjects: Aging - drug effects; Aging - metabolism; Aging - pathology; Animals; Anticonvulsants - pharmacology; Base Sequence; Calcium Channel Blockers - pharmacology; Calcium Channels, T-Type - deficiency; Calcium Channels, T-Type - genetics; Calcium Channels, T-Type - metabolism; Evoked Potentials, Auditory, Brain Stem - drug effects; Hair Cells, Auditory, Inner - pathology; Hair Cells, Auditory, Outer - pathology; Mice; Mice, Congenic; Mice, Knockout; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Presbycusis - metabolism; Presbycusis - pathology; Presbycusis - prevention & control; RNA - genetics; RNA - metabolism; Spiral Ganglion - drug effects; Spiral Ganglion - innervation; Spiral Ganglion - metabolism; Spiral Ganglion - pathology
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/j.heares.2011.05.010

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 v3.1, Ca v3.2, and Ca v3.3), based on their respective main pore-forming alpha subunits: α1G, α1H, and α1I. In the present study, we report a significant delay of age-related loss of cochlear function and preservation of spiral ganglion neurons in α1H null and heterozygous mice, clearly demonstrating an important role for Ca v3.2 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. ► Presbycusis is diminished in mice lacking Ca v3.3 T-type calcium channels. ► This delay of presbycusis is accompanied by preservation of spiral ganglion neurons. ► Anti-epileptic drugs blocking T-type calcium channels can also delay presbycusis.