title: Attenuation of hearing loss in DBA/2J mice by anti-apoptotic treatment.
abstract: DBA/2J mice are characterized by early onset hearing loss at about 3-4 weeks of age. Mutations in cadherin 23 (Cdh23) and fascin-2 (Fscn2) are responsible for the phenotypes, but the underlying mechanism is unknown. In the present study, DBA/2J mice displayed progressive hair cell loss and degeneration of spiral ganglion neurons (SGNs) after 2 weeks of age; however, the mRNA level of Caspase-3 in the inner ears was much higher at 2 weeks of age than that at 4 or 8 weeks of age. Moreover, transcriptional levels of Caspase-3 and Caspase-9 in the inner ears of DBA/2J mice were significantly higher than those of C57BL/6J mice at 2 or 8 weeks of age. Immunohistochemistry localized Caspase-3 and Caspase-9 mainly to the hair cells, SGNs and stria vascularis of the cochleae. To determine the significance of caspase-dependent apoptosis in the hearing loss, the pan-caspase inhibitor Z-VAD-FMK was given intraperitoneally to DBA/J2 mice over an 8-week period starting at one week of age. Blockage of caspases preserved hearing in the mice by more than 10 dB (dB) sound pressure level (SPL) of the ABR thresholds and significantly reduced outer hair cell loss at the basal turns of the cochleae. These results demonstrate that apoptosis in the cochleae of DBA/J2 mice contributes to the early onset of hearing loss, which can be attenuated by anti-apoptotic treatment.
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Department of Otorhinolaryngology-Head and Neck Surgery, Yuhuangding Hospital, 20 East Yuhuangding Road, Yantai 264000, Shandong, PR China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Hu
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Gao
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Department of Otorhinolaryngology-Head and Neck Surgery, Yuhuangding Hospital, 20 East Yuhuangding Road, Yantai 264000, Shandong, PR China. Electronic address: songxicheng@126.com.
authors.forename: Xicheng
authors.initials: X
authors.lastname: Song
authors.affiliation: Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China. Electronic address: hanfengchan@gmail.com.
authors.forename: Fengchan
authors.initials: F
authors.lastname: Han
mesh_terms: D000161:Acoustic Stimulation; D000590:Amino Acid Chloromethyl Ketones / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001309:Auditory Threshold; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D061945:Caspase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019610:Cytoprotection; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D016057:Evoked Potentials, Auditory, Brain Stem; D005786:Gene Expression Regulation; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D017084:Otoacoustic Emissions, Spontaneous; D010641:Phenotype; D013997:Time Factors
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9