title: Anti-epileptic drugs delay age-related loss of spiral ganglion neurons via T-type calcium channel.
abstract: 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: 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(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.
authors.affiliation: Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Debin
authors.initials: D
authors.lastname: Lei
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.forename: Philip
authors.initials: P
authors.lastname: Perez
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Ohlemiller
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Chen
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.forename: Aizhen Yang
authors.initials: AY
authors.lastname: Hood
authors.forename: Jianxin
authors.initials: J
authors.lastname: Bao
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001483:Base Sequence; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006199:Hair Cells, Auditory, Inner / Q000473:pathology; D018072:Hair Cells, Auditory, Outer / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011304:Presbycusis / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D013136:Spiral Ganglion / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism* / Q000473:pathology
chemical_list: D000927:Anticonvulsants; C498197:Cacna1g protein, mouse; C504883:Cacna1h protein, mouse; C534770:Cacna1i protein, mouse; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D012313:RNA