PMID- 23149719 OWN - NLM STAT- MEDLINE DCOM- 20130605 LR - 20211021 IS - 1432-0878 (Electronic) IS - 0302-766X (Print) IS - 0302-766X (Linking) VI - 351 IP - 1 DP - 2013 Jan TI - Developmental changes in the responsiveness of rat spiral ganglion neurons to neurotrophic factors in dissociated culture: differential responses for survival, neuritogenesis and neuronal morphology. PG - 15-27 LID - 10.1007/s00441-012-1526-1 [doi] AB - The way that the development of the inner ear innervation is regulated by various neurotrophic factors and/or their combinations at different postnatal developmental stages remains largely unclear. Moreover, survival and neuritogenesis in deafferented adult neurons is important for cochlear implant function. To address these issues, developmental changes in the responsiveness of postnatal rat spiral ganglion neurons (SGNs) to neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were examined by using a dissociated cell culture system. SGNs at postnatal day (P) 0, P5 and P20 (young adult) were cultured with the addition of NT-3, BDNF, or LIF or of a combination of NT-3 and BDNF (N + B) or of NT-3, BDNF and LIF (ALL factors). SGNs were analyzed for three parameters: survival, longest neurite length (LNL) and neuronal morphology. At P0, SGNs required exposure to N + B or ALL factors for enhanced survival and the ALL factors combination showed a synergistic effect much greater than the sum of the individual factors. At P5, SGNs responded to a wider range of treatment conditions for enhanced survival and combinations showed only an additive improvement over individual factors. The survival percentage of untreated SGNs was highest at P20 but combinations of neurotrophic factors were no more effective than individual factors. LNL of each SGN was enhanced by LIF alone or ALL factors at P0 and P5 but was suppressed by NT-3, BDNF and N + B at P5 in a dose-dependent manner. The LNL at P20 was enhanced by ALL factors and suppressed by N + B. Treatment with ALL factors increased the proportion of SGNs that had two or more primary neurites in all age groups. These findings suggest that NT-3, BDNF, LIF and their combinations predominantly support different ontogenetic events at different developmental stages in the innervation of the inner ear. FAU - Jin, Yulian AU - Jin Y AD - Department of Otolaryngology and Head and Neck Surgery, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan. FAU - Kondo, Kenji AU - Kondo K FAU - Ushio, Munetaka AU - Ushio M FAU - Kaga, Kimitaka AU - Kaga K FAU - Ryan, Allen F AU - Ryan AF FAU - Yamasoba, Tatsuya AU - Yamasoba T LA - eng GR - I01 BX001205/BX/BLRD VA/United States GR - R01 DC000129/DC/NIDCD NIH HHS/United States PT - Journal Article DEP - 20121113 PL - Germany TA - Cell Tissue Res JT - Cell and tissue research JID - 0417625 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Leukemia Inhibitory Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) SB - IM MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Cell Culture Techniques MH - Cell Shape/*drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Humans MH - Leukemia Inhibitory Factor/pharmacology MH - Nerve Growth Factors/*pharmacology MH - Neurites/drug effects/*metabolism MH - Neurogenesis/*drug effects MH - Neurotrophin 3/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Spiral Ganglion/*growth & development PMC - PMC3577061 MID - NIHMS438940 EDAT- 2012/11/15 06:00 MHDA- 2013/06/06 06:00 PMCR- 2013/08/01 CRDT- 2012/11/15 06:00 PHST- 2012/08/13 00:00 [received] PHST- 2012/10/24 00:00 [accepted] PHST- 2012/11/15 06:00 [entrez] PHST- 2012/11/15 06:00 [pubmed] PHST- 2013/06/06 06:00 [medline] PHST- 2013/08/01 00:00 [pmc-release] AID - 10.1007/s00441-012-1526-1 [doi] PST - ppublish SO - Cell Tissue Res. 2013 Jan;351(1):15-27. doi: 10.1007/s00441-012-1526-1. Epub 2012 Nov 13.