title: Up-regulation of GAP-43 in the chinchilla ventral cochlear nucleus after carboplatin-induced hearing loss: correlations with inner hair cell loss and outer hair cell loss.
abstract: Inner ear damage leads to nerve fiber growth and synaptogenesis in the ventral cochlear nucleus (VCN). In this study, we documented the relationship between hair cell loss patterns and synaptic plasticity in the chinchilla VCN using immunolabeling of the growth associated protein-43 (GAP-43), a protein associated with axon outgrowth and modification of presynaptic endings. Unilateral round window application of carboplatin caused hair cell degeneration in which inner hair cells (IHC) were more vulnerable than outer hair cells (OHC). One month after carboplatin treatment (0.5-5 mg/ml), we observed varying patterns of cochlear hair cell loss and GAP-43 expression in VCN. Both IHC loss and OHC loss were strongly correlated with increased GAP-43 immunolabeling in the ipsilateral VCN. We speculate that two factors might promote the expression of GAP-43 in the VCN; one is the loss of afferent input through IHC or the associated type I auditory nerve fibers. The other occurs when the medial olivocochlear efferent neurons lose their cochlear targets, the OHC, and may as compensation increase their synapse numbers in the VCN.
authors.affiliation: Center for Hearing and Deafness, SUNY at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA. skkraus@buffalo.edu
authors.forename: K S
authors.initials: KS
authors.lastname: Kraus
authors.forename: D
authors.initials: D
authors.lastname: Ding
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: M H
authors.initials: MH
authors.lastname: Kermany
authors.forename: S
authors.initials: S
authors.lastname: Mitra
authors.forename: R J
authors.initials: RJ
authors.lastname: Salvi
mesh_terms: D000818:Animals; D016190:Carboplatin / Q000009:adverse effects*; D002682:Chinchilla; D003056:Cochlear Nerve / Q000378:metabolism; D017626:Cochlear Nucleus / Q000378:metabolism*; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism*; D006199:Hair Cells, Auditory, Inner / Q000473:pathology*; D018072:Hair Cells, Auditory, Outer / Q000473:pathology*; D034381:Hearing Loss / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D009473:Neuronal Plasticity; D012405:Round Window, Ear / Q000473:pathology; D013569:Synapses / Q000473:pathology; D015854:Up-Regulation
chemical_list: D019922:GAP-43 Protein; D016190:Carboplatin