title: Apoptosis-inducing factor and calpain upregulation in glutamate-induced injury of rat spiral ganglion neurons.
abstract: Spiral ganglion neuron (SGN) damage and apoptosis can lead to noise-induced hearing loss, age-associated hearing loss and, in certain cases, auditory neuropathy. The apoptosis-inducing factor (AIF)-associated pathway may be important in this process. The present study aimed to investigate the expression levels of AIF and calpain in damaged SGNs. Glutamate (Glu) perfusion and cell culture in different concentrations of Glu were performed to damage the SGNs of Sprague-Dawley (SD) rats, with saline water used as a control Different concentrations (5, 10, 20 and 40 mM) of Glu were injected into the cochlear tympanic canal of 18 SD rats, and 10, 20 and 40 mM Glu were added to SGN cultures. Auditory brainstem responses (ABR) were measured prior to and 2 days following the injection of Glu. Immunofluorescent staining was used to detect the SGN damage and the expression levels of AIF and calpain in vivo and in in vitro. Transmission electron microscopy (TEM) was used to measure cell apoptosis and reverse transcription-quantitative polymerase chain reaction was used to analyse the gene expression levels of AIF and calpain in the damaged SGNs. The TEM identified mitochondrial vacuolisation, swelling of the SGN and heterochromatin formation. Injection of Glu reduced the number of SGNs and induced apoptosis. AIF was observed to translocate into the nuclei of the SGNs in the 20 and 40 mM Glu groups, and the expression levels of AIF and calpain were markedly upregulated in the modiolus of the Glu-damaged SGNs. The upregulation of AIF and calpain may be important in the process of SGN damage and apoptosis.
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Zhong-Jia
authors.initials: ZJ
authors.lastname: Ding
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Outpatient Department, Logistics Academy, Beijing 100858, P.R. China.
authors.forename: Xiao-Xu
authors.initials: XX
authors.lastname: Tang
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Song
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Ren-Feng
authors.initials: RF
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Mi
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Fu-Quan
authors.initials: FQ
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Qiu
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D051033:Apoptosis Inducing Factor; D018698:Glutamic Acid; D002154:Calpain; D053148:Caspase 3