title: Developmental changes in the protective effect of exogenous brain-derived neurotrophic factor and neurotrophin-3 against ototoxic drugs in cultured rat vestibular ganglion neurons.
abstract: We examine developmental changes in the responsiveness of rat vestibular ganglion neurons (VGNs) to two neurotrophic factors (NTFs), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and investigate the protective effects of these NTFs against ototoxic drugs during postnatal development in dissociated cultures. VGNs were obtained from rats on postnatal days (P) 1, 3, 7 and 14. BDNF facilitated neuronal survival as well as neurite sprouting of VGNs obtained from younger rats (P1 and P3), whereas these effects were not observed in older rats (P7 and P14). BDNF was also effective in facilitating neurite extension in VGNs at each of the postnatal ages. NT-3 also facilitated neuronal survival and neurite extension of VGNs from younger rats but these effects were significantly smaller than those of BDNF (p < 0.05). The protective effects of BDNF and NT-3 against ototoxic drugs, gentamicin and cisplatin, were also age-dependent: they were effective for neuronal survival, neurite sprouting and neurite extension in VGNs from younger rats, whereas these effects tended to disappear in VGNs from older rats. Analysis of the changes in the expression of the receptors of NTFs revealed that expression of TrkB and TrkC proteins and their mRNA did not change during the developmental period, whereas expression of p75(NTR) protein was down-regulated together with that of p75(NTR) mRNA during the developmental period. Developmental changes in the responsiveness to exogenous NTFs in VGNs, which is not caused by the changes of their receptors but probably caused by changes in the intracellular signaling pathways, should be taken into consideration in the prevention of neuronal degeneration caused by ototoxic drugs.
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Inoue
authors.forename: Shinichi
authors.initials: S
authors.lastname: Iwasaki
authors.forename: Chisato
authors.initials: C
authors.lastname: Fujimoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakajima
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamasoba
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D003432:Cross-Linking Reagents / Q000633:toxicity; D015536:Down-Regulation; D005839:Gentamicins / Q000633:toxicity*; D016501:Neurites / Q000473:pathology; D020933:Neurotrophin 3 / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020800:Receptor, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D020813:Receptor, trkB / Q000096:biosynthesis / Q000235:genetics; D020812:Receptor, trkC / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D014725:Vestibular Nerve / Q000196:embryology* / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003432:Cross-Linking Reagents; D005839:Gentamicins; D020933:Neurotrophin 3; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D020813:Receptor, trkB; D020812:Receptor, trkC; D002945:Cisplatin