title: Otoprotective effects of mouse nerve growth factor in DBA/2J mice with early-onset progressive hearing loss.
abstract: As it displays progressive hair-cell loss and degeneration of spiral ganglion neurons (SGNs) characterized by early-onset progressive hearing loss (ePHL), DBA/2J is an inbred mouse strain widely used in hearing research. Mouse nerve growth factor (mNGF), as a common exogenous nerve growth factor (NGF), has been studied extensively for its ability to promote neuronal survival and growth. To determine whether mNGF can ameliorate progressive hearing loss (PHL) in DBA/2J mice, saline or mNGF was given to DBA/2J mice of either sex by daily intramuscular injection from the 1st to the 9th week after birth. At 5, 7, and 9 weeks of age, in comparison with vehicle groups, mNGF groups experienced decreased auditory-evoked brainstem response (ABR) thresholds and increased distortion product otoacoustic emission (DPOAE) amplitudes, the prevention of hair cell loss, and the inhibition of apoptosis of SGNs. Downregulation of Bak/Bax and Caspase genes and proteins in cochleae of mice receiving the mNGF treatment was detected by real-time PCR, Western blot, and immunohistochemistry. This suggests that the Bak-dependent mitochondrial apoptosis pathway may be involved in the otoprotective mechanism of mNGF in progressive hearing loss of DBA/2J mice. Our results demonstrate that mNGF can act as an otoprotectant in the DBA/2J mice for the early intervention of PHL and, thus, could become of great value in clinical applications. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai, 264003, Shandong, PR China.|Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Affiliated Hospital of Binzhou Medical University, Binzhou, 256600, Shandong, PR China.
authors.forename: Qingzhu
authors.identifier: 0000-0002-2685-2303
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Affiliated Hospital of Binzhou Medical University, Binzhou, 256600, Shandong, PR China.
authors.forename: Hongchun
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai, 264003, Shandong, PR China.
authors.forename: Tihua
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai, 264003, Shandong, PR China.|Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Affiliated Hospital of Binzhou Medical University, Binzhou, 256600, Shandong, PR China.|Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Affiliated Hospital of Binzhou Medical University, Binzhou, 256600, Shandong, PR China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors.forename: Andi
authors.initials: A
authors.lastname: Wang
authors.affiliation: Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai, 264003, Shandong, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai, 264003, Shandong, PR China.|Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Affiliated Hospital of Binzhou Medical University, Binzhou, 256600, Shandong, PR China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors.forename: Qingyin
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000818:Animals; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects*; D034381:Hearing Loss / Q000473:pathology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D020932:Nerve Growth Factor / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D013136:Spiral Ganglion / Q000187:drug effects*
chemical_list: D018696:Neuroprotective Agents; D020932:Nerve Growth Factor
keywords: apoptosis; hair cells; mitochondrial pathway; mouse model; mouse nerve growth factor; progressive hearing loss; spiral ganglion neurons