TY - JOUR
T1 - Anti-epileptic drugs delay age-related loss of spiral ganglion neurons via T-type calcium channel
AU - Lei, Debin
AU - Gao, Xia
AU - Perez, Philip
AU - Ohlemiller, Kevin K.
AU - Chen, Chien Chang
AU - Campbell, Kevin P.
AU - Hood, Aizhen Yang
AU - Bao, Jianxin
N1 - Funding Information:
We thank R. Chole, K. Evason, and K. Kornfeld for helpful discussions. We are also grateful to B. Bohne, R. Davis, D. Dickman, and D. Whitlon for providing comments on the manuscript. This work was supported by grants from the National Organization for Hearing Research Foundation, NIH NIA ( R01AG024250 ), and NIH NIDCD ( R21DC010489 ) to J.B., and core grants from NIH NIDCD ( P30DC004665 ) and NIH NINDS ( P30NS057105 ).
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/79960997905
U2 - 10.1016/j.heares.2011.05.010
DO - 10.1016/j.heares.2011.05.010
M3 - Article
C2 - 21640179
AN - SCOPUS:79960997905
SN - 0378-5955
VL - 278
SP - 106
EP - 112
JO - Hearing research
JF - Hearing research
IS - 1-2
ER -