PMID- 20216530 OWN - NLM STAT- MEDLINE DCOM- 20101005 LR - 20220129 IS - 1525-0024 (Electronic) IS - 1525-0016 (Print) IS - 1525-0016 (Linking) VI - 18 IP - 6 DP - 2010 Jun TI - Effects of localized neurotrophin gene expression on spiral ganglion neuron resprouting in the deafened cochlea. PG - 1111-22 LID - 10.1038/mt.2010.28 [doi] AB - A cochlear implant may be used to electrically stimulate spiral ganglion neurons (SGNs) in people with severe sensorineural hearing loss (SNHL). However, these neurons progressively degenerate after SNHL due to loss of neurotrophins normally supplied by sensory hair cells (HCs). Experimentally, exogenous neurotrophin administration prevents SGN degeneration but can also result in abnormal resprouting of their peripheral fibers. This study aimed to create a target-derived neurotrophin source to increase neuron survival and redirect fiber resprouting following SNHL. Adenoviral (Ad) vectors expressing green fluorescent protein (GFP) alone or in combination with brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT3) were injected into the cochlear scala tympani or scala media of guinea-pigs (GPs) deafened via aminoglycosides for 1 week. After 3 weeks, cochleae were examined for gene expression, neuron survival, and the projection of peripheral fibers in response to gene expression. Injection of vectors into the scala media resulted in more localized gene expression than scala tympani injection with gene expression consistently observed within the partially degenerated organ of Corti. There was also greater neuron survival and evidence of localized fiber responses to neurotrophin-expressing cells within the organ of Corti from scala media injections (P < 0.05), a first step in promoting organized resprouting of auditory peripheral fibers via gene therapy. FAU - Wise, Andrew K AU - Wise AK AD - Bionic Ear Institute, East Melbourne, Victoria, Australia. FAU - Hume, Clifford R AU - Hume CR FAU - Flynn, Brianna O AU - Flynn BO FAU - Jeelall, Yogesh S AU - Jeelall YS FAU - Suhr, Courtney L AU - Suhr CL FAU - Sgro, Beatrice E AU - Sgro BE FAU - O'Leary, Stephen J AU - O'Leary SJ FAU - Shepherd, Robert K AU - Shepherd RK FAU - Richardson, Rachael T AU - Richardson RT LA - eng GR - P30 HD-02774/HD/NICHD NIH HHS/United States GR - DC-006437/DC/NIDCD NIH HHS/United States GR - P30 DC-04661/DC/NIDCD NIH HHS/United States GR - G39/ACT_/RNID/United Kingdom GR - G30/ACT_/RNID/United Kingdom GR - P30 DC004661/DC/NIDCD NIH HHS/United States GR - K08 DC006437/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100309 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Adenoviridae/genetics MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics MH - Cell Survival MH - Cochlea/metabolism/*pathology MH - Deafness/*genetics MH - Female MH - Ganglia/cytology/*metabolism MH - Gene Expression Regulation MH - Genetic Vectors MH - Green Fluorescent Proteins/genetics MH - Guinea Pigs MH - Humans MH - Male MH - Neurons/*metabolism PMC - PMC2889745 EDAT- 2010/03/11 06:00 MHDA- 2010/10/06 06:00 PMCR- 2011/06/01 CRDT- 2010/03/11 06:00 PHST- 2010/03/11 06:00 [entrez] PHST- 2010/03/11 06:00 [pubmed] PHST- 2010/10/06 06:00 [medline] PHST- 2011/06/01 00:00 [pmc-release] AID - S1525-0016(16)31050-4 [pii] AID - 10.1038/mt.2010.28 [doi] PST - ppublish SO - Mol Ther. 2010 Jun;18(6):1111-22. doi: 10.1038/mt.2010.28. Epub 2010 Mar 9.