title: Cell proliferation in the cochlear nucleus following acoustic trauma in rat.
abstract: Our previous studies have suggested that surgical lesions of the rat cochlea induce cell proliferation in the cochlear nucleus (CN) that may be related to neurogenesis. The aim of the present study was to further investigate the nature of cell proliferation in the CN, following acoustic trauma that has previously been shown to induce tinnitus in rats. Rats were subjected either to a unilateral acoustic trauma (16-kHz pure tone, 115dB for 1h under anesthesia) or a sham procedure. Bromodeoxyuridine (BrdU) immunohistochemistry was used to measure cell proliferation and newborn cell survival; an antibody to interleukin-6 was used to investigate inflammatory responses; and double immunolabeling for BrdU and Ki-67, BrdU and CD-11b, and BrdU and doublecortin (DCX), was used to investigate the origin of the proliferating cells. There was a time-dependent increase in the number of BrdU(+ve) cells in the CN following acoustic trauma; however, the number of BrdU(+ve) cells that survived was comparable to that of control animals at 4 weeks post-trauma. Cell proliferation was unlikely to be due to proliferating inflammatory cells as a result of a trauma-induced inflammatory response as the IL-6 expression level was comparable between sham and exposed groups. Immunolabeling revealed the BrdU(+ve) cells to co-express Ki-67 and DCX, but not CD-11b. However, there was no difference in DCX expression between sham and exposed animals. The results suggest that DCX-expressing cells in the CN may proliferate in response to acoustic trauma; however, the proportion of cells proliferating and the survival rate of the newborn cells may not support functional neurogenesis in the CN.
authors.affiliation: Dept. of Pharmacology and Toxicology, School of Medical Sciences and the Brain Health Research Centre, University of Otago, Dunedin, New Zealand. Electronic address: yiwen.zheng@otago.ac.nz.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Dept. of Pharmacology and Toxicology, School of Medical Sciences and the Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: H
authors.initials: H
authors.lastname: Smithies
authors.affiliation: Dept. of Pharmacology and Toxicology, School of Medical Sciences and the Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: P
authors.initials: P
authors.lastname: Aitken
authors.affiliation: Dept. of Pharmacology and Toxicology, School of Medical Sciences and the Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: C
authors.initials: C
authors.lastname: Gliddon
authors.affiliation: Dept. of Pharmacology and Toxicology, School of Medical Sciences and the Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: L
authors.initials: L
authors.lastname: Stiles
authors.affiliation: Dept. of Pharmacology and Toxicology, School of Medical Sciences and the Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: C L
authors.initials: CL
authors.lastname: Darlington
authors.affiliation: Dept. of Pharmacology and Toxicology, School of Medical Sciences and the Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: P F
authors.initials: PF
authors.lastname: Smith
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology*; D017626:Cochlear Nucleus / Q000473:pathology*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D016057:Evoked Potentials, Auditory, Brain Stem; D006317:Hearing Loss, Noise-Induced / Q000473:pathology* / Q000503:physiopathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D039481:CD11b Antigen; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D001973:Bromodeoxyuridine
keywords: BrdU; acoustic trauma; auditory system; cell proliferation; cochlear nucleus; neurogenesis