{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T07:07:48Z","timestamp":1763017668137},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T00:00:00Z","timestamp":1473724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T00:00:00Z","timestamp":1473724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gene therapy can take advantage of the skeletal muscles\/motor neurons anatomical relationship to restrict gene expression to the spinal cord ventral horn. Furthermore, recombinant adenoviruses are attractive viral-vectors as they permit spatial and temporal modulation of transgene expression. In the literature, however, several inconsistencies exist with regard to the intramuscular delivery parameters of adenoviruses. The present study is an evaluation of the optimal injection sites on skeletal muscle, time course of expression and mice\u2019s age for maximum transgene expression in motor neurons. Targeting motor end plates yielded a 2.5-fold increase in the number of transduced motor neurons compared to injections performed away from this region. Peak adenoviral transgene expression in motor neurons was detected after seven days. Further, greater numbers of transduced motor neurons were found in juvenile (3\u20137 week old) mice as compared with adults (8+ weeks old). Adenoviral injections produced robust transgene expression in motor neurons and skeletal myofibres. In addition, dendrites of transduced motor neurons were shown to extend well into the white matter where the descending motor pathways are located. These results also provide evidence that intramuscular delivery of adenovirus can be a suitable gene therapy approach to treat spinal cord injury.<\/jats:p>","DOI":"10.1038\/srep33058","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T11:31:35Z","timestamp":1473766295000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Targeting Motor End Plates for Delivery of Adenoviruses: An Approach to Maximize Uptake and Transduction of Spinal Cord Motor Neurons"],"prefix":"10.1038","volume":"6","author":[{"given":"Andrew Paul","family":"Tosolini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9e","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,9,13]]},"reference":[{"key":"BFsrep33058_CR1","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.1523\/JNEUROSCI.19-11-04370.1999","volume":"19","author":"Y Liu","year":"1999","unstructured":"Liu, Y., Kim, D., Himes, B. T., Chow, S. Y., Schallert, T., Murray, M. et al. Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function. Journal of Neuroscience 19(11), 4370\u20134387 (1999).","journal-title":"Journal of Neuroscience"},{"key":"BFsrep33058_CR2","doi-asserted-by":"crossref","first-page":"7045","DOI":"10.1523\/JNEUROSCI.23-18-07045.2003","volume":"23","author":"MJ Ruitenberg","year":"2003","unstructured":"Ruitenberg, M. J., Plant, G. W., Hamers, F. P. T., Wortel, J., Blits, B., Dijkhuizen, P. A. et al. Ex vivo adenoviral vector-mediated neurotrophin gene transfer to olfactory ensheathing glia: effects on rubrospinal tract regeneration, lesion size, and functional recovery after implantation in the injured rat spinal cord. Journal of Neuroscience, 23(18), 7045\u20137058 (2003).","journal-title":"Journal of Neuroscience"},{"key":"BFsrep33058_CR3","doi-asserted-by":"crossref","first-page":"9713","DOI":"10.1523\/JNEUROSCI.0734-06.2006","volume":"26","author":"L Taylor","year":"2006","unstructured":"Taylor, L., Jones, L., Tuszynski, M. H. & Blesch, A. Neurotrophin-3 gradients established by lentiviral gene delivery promote short-distance axonal bridging beyond cellular grafts in the injured spinal cord. Journal of Neuroscience 26(38), 9713\u20139721 (2006).","journal-title":"Journal of Neuroscience"},{"key":"BFsrep33058_CR4","doi-asserted-by":"crossref","unstructured":"Gransee, H. M., Zhan, W.-Z., Sieck, G. C. & Mantilla, C. B. Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury. Journal of Neurotrauma (2014).","DOI":"10.1089\/neu.2014.3464"},{"key":"BFsrep33058_CR5","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1089\/neu.2008.0807","volume":"26","author":"J Fortun","year":"2009","unstructured":"Fortun, J., Puzis, R., Pearse, D. D., Gage, F. H. & Bunge, M. B. Muscle injection of AAV-NT3 promotes anatomical reorganization of CST axons and improves behavioral outcome following SCI. Journal of Neurotrauma 26(7), 941\u2013953 (2009).","journal-title":"Journal of Neurotrauma"},{"issue":"24","key":"BFsrep33058_CR6","doi-asserted-by":"crossref","first-page":"8208","DOI":"10.1523\/JNEUROSCI.0308-12.2012","volume":"32","author":"P Lu","year":"2012","unstructured":"Lu, P., Blesch, A., Graham, L., Wang, Y., Samara, R., Banos, K. et al. Motor axonal regeneration after partial and complete spinal cord transection. Journal of Neuroscience 32(24), 8208\u20138218 (2012).","journal-title":"Journal of Neuroscience"},{"key":"BFsrep33058_CR7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3389\/fneur.2013.00187","volume":"4","author":"K Fouad","year":"2013","unstructured":"Fouad, K., Bennett, D. J., Vavrek, R. & Blesch, A. Long-term viral brain-derived neurotrophic factor delivery promotes spasticity in rats with a cervical spinal cord hemisection. Frontiers in Neurology 4, 187 (2013).","journal-title":"Frontiers in Neurology"},{"key":"BFsrep33058_CR8","doi-asserted-by":"crossref","first-page":"e88833","DOI":"10.1371\/journal.pone.0088833","volume":"9","author":"E Ziemli\u0144ska","year":"2014","unstructured":"Ziemli\u0144ska, E., K\u00fcgler, S., Schachner, M., Wewi\u00f3r, I., Czarkowska-Bauch, J. & Skup, M. Overexpression of BDNF Increases Excitability of the Lumbar Spinal Network and Leads to Robust Early Locomotor Recovery in Completely Spinalized Rats. PLoS ONE 9(2), e88833 (2014).","journal-title":"PLoS ONE"},{"key":"BFsrep33058_CR9","doi-asserted-by":"crossref","first-page":"10535","DOI":"10.1523\/JNEUROSCI.1903-07.2007","volume":"27","author":"A Blesch","year":"2007","unstructured":"Blesch, A. & Tuszynski, M. H. Transient Growth Factor Delivery Sustains Regenerated Axons after Spinal Cord Injury. Journal of Neuroscience 27(39), 10535\u201310545 (2007).","journal-title":"Journal of Neuroscience"},{"key":"BFsrep33058_CR10","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/(SICI)1097-4547(19981115)54:4<554::AID-JNR12>3.0.CO;2-M","volume":"54","author":"Y Zhang","year":"1998","unstructured":"Zhang, Y., Dijkhuizen, P. A., Anderson, P. N., Lieberman, A. R. & Verhaagen, J. NT-3 delivered by an adenoviral vector induces injured dorsal root axons to regenerate into the spinal cord of adult rats. Journal of Neuroscience Research 54(4), 554\u2013562 (1998).","journal-title":"Journal of Neuroscience Research"},{"key":"BFsrep33058_CR11","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1089\/089771504322972112","volume":"21","author":"M Koda","year":"2004","unstructured":"Koda, M., Hashimoto, M., Murakami, M., Yoshinaga, K., Ikeda, O., Yamazaki, M. et al. Adenovirus vector-mediated in vivo gene transfer of brain-derived neurotrophic factor (BDNF) promotes rubrospinal axonal regeneration and functional recovery after complete transection of the adult rat spinal cord. Journal of Neurotrauma 21(3), 329\u2013337 (2004).","journal-title":"Journal of Neurotrauma"},{"key":"BFsrep33058_CR12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/(SICI)1097-4547(19990115)55:2<147::AID-JNR2>3.0.CO;2-8","volume":"55","author":"GM Smith","year":"1999","unstructured":"Smith, G. M. & Romero, M. I. Adenoviral-mediated gene transfer to enhance neuronal survival, growth, and regeneration. Journal of Neuroscience Research 55(2), 147\u2013157 (1999).","journal-title":"Journal of Neuroscience Research"},{"key":"BFsrep33058_CR13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1089\/10430340152712638","volume":"13","author":"B-G Harvey","year":"2004","unstructured":"Harvey, B.-G., Maroni, J., O\u2019Donoghue, K. A., Chu, K. W., Muscat, J. C., Pippo, A. L. et al. Safety of Local Delivery of Low- and Intermediate-Dose Adenovirus Gene Transfer Vectors to Individuals with a Spectrum of Morbid Conditions. Human Gene Therapy 13(1), 15\u201363 (2004).","journal-title":"Human Gene Therapy"},{"key":"BFsrep33058_CR14","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1007\/s11033-008-9315-3","volume":"36","author":"Z-J Yang","year":"2008","unstructured":"Yang, Z.-J., Zhang, Y.-R., Chen, B., Zhang, S.-L., Jia, E.-Z., Wang, L.-S. et al. Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease. Molecular Biology Reports 36(6), 1323\u20131329 (2008).","journal-title":"Molecular Biology Reports"},{"key":"BFsrep33058_CR15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1089\/hum.2013.2527","volume":"25","author":"RG Crystal","year":"2014","unstructured":"Crystal, R. G. Adenovirus: The First Effective In Vivo Gene Delivery Vector. Human Gene Therapy, 25(1), 3\u201311 (2014).","journal-title":"Human Gene Therapy"},{"key":"BFsrep33058_CR16","doi-asserted-by":"crossref","unstructured":"Morris, R. Neurotoxicity and Neuroprotection in Spinal Cord Injury. In Handbook of Neurotoxicity (pp. 1457\u20131482). New York, NY: Springer: New York, (2014).","DOI":"10.1007\/978-1-4614-5836-4_135"},{"key":"BFsrep33058_CR17","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.nbd.2014.10.025","volume":"73","author":"X Ding","year":"2015","unstructured":"Ding, X., Cai, J., Li, S., Liu, X. D., Wan, Y. & Xing, G. G. BDNF contributes to the development of neuropathic pain by induction of spinal long-term potentiation via SHP2 associated GluN2B-containing NMDA receptors activation in rats with spinal nerve ligation. Neurobiol Disease 73, 428\u2013451 (2015).","journal-title":"Neurobiol Disease"},{"key":"BFsrep33058_CR18","doi-asserted-by":"crossref","unstructured":"Eleftheriadou, I., Trabalza, A., Ellison, S. M., Gharun, K. & Mazarakis, N. D. Specific Retrograde Transduction of Spinal Motor Neurons Using Lentiviral Vectors Targeted to Presynaptic NMJ Receptors. Molecular Therapy: the Journal of the American Society of Gene Therapy (2014).","DOI":"10.1038\/mt.2014.49"},{"key":"BFsrep33058_CR19","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1126\/science.1086137","volume":"301","author":"BK Kaspar","year":"2003","unstructured":"Kaspar, B. K., Ll\u00e1do, J., Sherkat, N., Rothstein, J. D. & Gage, F. H. Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science 301(5634), 839\u2013842 (2003).","journal-title":"Science"},{"key":"BFsrep33058_CR20","doi-asserted-by":"crossref","first-page":"25960","DOI":"10.1038\/srep25960","volume":"6","author":"I Allodi","year":"2016","unstructured":"Allodi, I., Comley, L., Nichterwitz, S., Nizzardo, M., Simone, C., Benitez, J. A. et al. Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS. Scientific Reports 6, 25960 (2016).","journal-title":"Scientific Reports"},{"key":"BFsrep33058_CR21","first-page":"132","volume":"2","author":"GD Ghadge","year":"1995","unstructured":"Ghadge, G. D., Roos, R. P., Kang, U. J., Wollmann, R., Fishman, P. S., Kalynych, A. M. et al. CNS gene delivery by retrograde transport of recombinant replication-defective adenoviruses. Gene Therapy 2(2), 132\u2013137 (1995).","journal-title":"Gene Therapy"},{"key":"BFsrep33058_CR22","doi-asserted-by":"crossref","first-page":"6504","DOI":"10.1523\/JNEUROSCI.17-17-06504.1997","volume":"17","author":"BJ Baumgartner","year":"1997","unstructured":"Baumgartner, B. J. & Shine, H. D. Targeted transduction of CNS neurons with adenoviral vectors carrying neurotrophic factor genes confers neuroprotection that exceeds the transduced population. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience 17(17), 6504\u20136511 (1997).","journal-title":"The Journal of Neuroscience: the Official Journal of the Society for Neuroscience"},{"key":"BFsrep33058_CR23","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nm0497-429","volume":"3","author":"G Haase","year":"1997","unstructured":"Haase, G., Kennel, P., Pettmann, B., Vigne, E., Akli, S., Revah, F. et al. Gene therapy of murine motor neuron disease using adenoviral vectors for neurotrophic factors. Nature Medicine 3(4), 429\u2013436 (1997).","journal-title":"Nature Medicine"},{"key":"BFsrep33058_CR24","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1073\/pnas.97.1.442","volume":"97","author":"M Glatzel","year":"2000","unstructured":"Glatzel, M., Flechsig, E., Navarro, B., Klein, M. A., Paterna, J. C., B\u00fceler, H. & Aguzzi, A. Adenoviral and adeno-associated viral transfer of genes to the peripheral nervous system. Proceedings of the National Academy of Sciences of the United States of America, 97(1), 442\u2013447 (2000).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep33058_CR25","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1097\/BRS.0b013e3182600ef7","volume":"37","author":"K Uchida","year":"2012","unstructured":"Uchida, K., Nakajima, H., Hirai, T., Yayama, T., Chen, K., Guerrero, A. R. et al. The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy\/twy mice. Spine 37(26), 2125\u20132135 (2012).","journal-title":"Spine"},{"key":"BFsrep33058_CR26","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1006\/exnr.1998.6878","volume":"153","author":"BJ Baumgartner","year":"1998","unstructured":"Baumgartner, B. J. & Shine, H. D. Neuroprotection of spinal motoneurons following targeted transduction with an adenoviral vector carrying the gene for glial cell line-derived neurotrophic factor. Experimental Neurology 153(1), 102\u2013112 (1998a).","journal-title":"Experimental Neurology"},{"key":"BFsrep33058_CR27","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/(SICI)1097-4547(19981215)54:6<766::AID-JNR4>3.0.CO;2-A","volume":"54","author":"BJ Baumgartner","year":"1998","unstructured":"Baumgartner, B. J. & Shine, H. D. Permanent rescue of lesioned neonatal motoneurons and enhanced axonal regeneration by adenovirus-mediated expression of glial cell-line-derived neurotrophic factor. Journal of Neuroscience Research 54(6), 766\u2013777 (1998b).","journal-title":"Journal of Neuroscience Research"},{"key":"BFsrep33058_CR28","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00429-002-0233-1","volume":"205","author":"VN Martinov","year":"2002","unstructured":"Martinov, V. N., Sefland, I., Walaas, S. I., L\u00f8mo, T., Nj\u00e5, A. & Hoover, F. Targeting functional subtypes of spinal motoneurons and skeletal muscle fibres in vivo by intramuscular injection of adenoviral and adeno-associated viral vectors. Anatomy and Embryology 205(3), 215\u2013221 (2002).","journal-title":"Anatomy and Embryology"},{"key":"BFsrep33058_CR29","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/BRS.0b013e3181b8e89b","volume":"35","author":"H Nakajima","year":"2010","unstructured":"Nakajima, H., Uchida, K., Yayama, T., Kobayashi, S., Guerrero, A. R., Furukawa, S. & Baba, H. Targeted retrograde gene delivery of brain-derived neurotrophic factor suppresses apoptosis of neurons and oligodendroglia after spinal cord injury in rats. Spine 35(5), 497\u2013504 (2010).","journal-title":"Spine"},{"key":"BFsrep33058_CR30","doi-asserted-by":"crossref","first-page":"743","DOI":"10.4103\/1673-5374.182698","volume":"11","author":"AP Tosolini","year":"2016","unstructured":"Tosolini, A. P. & Morris, R. Viral-mediated gene therapy for spinal cord injury (SCI) from a translational neuroanatomical perspective. Neural Regen Res 11(5), 743\u2013744 (2016).","journal-title":"Neural Regen Res"},{"key":"BFsrep33058_CR31","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neulet.2005.05.012","volume":"385","author":"H Nakajima","year":"2005","unstructured":"Nakajima, H., Uchida, K., Kobayashi, S., Kokubo, Y., Yayama, T., Sato, R. & Baba, H. Targeted retrograde gene delivery into the injured cervical spinal cord using recombinant adenovirus vector. Neuroscience Letters 385(1), 30\u201335 (2005).","journal-title":"Neuroscience Letters"},{"key":"BFsrep33058_CR32","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1089\/neu.2006.0004","volume":"24","author":"H Nakajima","year":"2007","unstructured":"Nakajima, H., Uchida, K., Kobayashi, S., Inukai, T., Horiuchi, Y., Yayama, T. et al. Rescue of Rat Anterior Horn Neurons after Spinal Cord Injury by Retrograde Transfection of Adenovirus Vector Carrying Brain-Derived Neurotrophic Factor Gene. Journal of Neurotrauma 24(4), 703\u2013712 (2007).","journal-title":"Journal of Neurotrauma"},{"key":"BFsrep33058_CR33","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1002\/jnr.21627","volume":"86","author":"K Uchida","year":"2008","unstructured":"Uchida, K., Nakajima, H., Inukai, T., Takamura, T., Kobayashi, S., Furukawa, S. & Baba, H. Adenovirus-mediated retrograde transfer of neurotrophin-3 gene enhances survival of anterior horn neurons oftwy\/twy mice with chronic mechanical compression of the spinal cord. Journal of Neuroscience Research 86(8), 1789\u20131800 (2008).","journal-title":"Journal of Neuroscience Research"},{"key":"BFsrep33058_CR34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuroscience.2011.10.054","volume":"200","author":"AP Tosolini","year":"2012","unstructured":"Tosolini, A. P. & Morris, R. Spatial characterization of the motor neuron columns supplying the rat forelimb. Neuroscience, 200, 19\u201330 (2012).","journal-title":"Neuroscience"},{"key":"BFsrep33058_CR35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fneur.2013.00058","volume":"4","author":"AP Tosolini","year":"2013","unstructured":"Tosolini, A. P., Mohan, R. & Morris, R. Targeting the Full Length of the Motor End Plate Regions in the Mouse Forelimb Increases the Uptake of Fluoro-Gold into Corresponding Spinal Cord Motor Neurons. Frontiers in Neurology 4, 1\u201310 (2013).","journal-title":"Frontiers in Neurology"},{"key":"BFsrep33058_CR36","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.neuroscience.2014.05.045","volume":"274","author":"R Mohan","year":"2014","unstructured":"Mohan, R., Tosolini, A. P. & Morris, R. Targeting the motor end plates in the mouse hindlimb gives access to a greater number of spinal cord motor neurons: An approach to maximize retrograde transport. Neuroscience 274, 318\u2013330 (2014).","journal-title":"Neuroscience"},{"key":"BFsrep33058_CR37","doi-asserted-by":"crossref","unstructured":"Mohan, R., Tosolini, A. P. & Morris, R. Intramuscular Injections Along the Motor End Plates: a Minimally Invasive Approach to Shuttle Tracers Directly into Motor Neurons. J. Vis. Exp. e52846 (2015a)","DOI":"10.3791\/52846"},{"key":"BFsrep33058_CR38","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.neuroscience.2015.08.030","volume":"307","author":"R Mohan","year":"2015","unstructured":"Mohan, R., Tosolini, A. P. & Morris, R. Segmental distribution of the motor neuron columns that supply the rat hindlimb: A muscle\/motor neuron tract-tracing analysis targeting the motor end plates. Neuroscience, 307, 98\u2013108 (2015).","journal-title":"Neuroscience"},{"key":"BFsrep33058_CR39","doi-asserted-by":"crossref","first-page":"10122","DOI":"10.1128\/JVI.78.18.10122-10132.2004","volume":"78","author":"SA Kelkar","year":"2004","unstructured":"Kelkar, S. A., Pfister, K. K., Crystal, R. G. & Leopold, P. L. Cytoplasmic dynein mediates adenovirus binding to microtubules. Journal of Virology 78(18), 10122\u201310132 (2004).","journal-title":"Journal of Virology"},{"key":"BFsrep33058_CR40","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.nmd.2005.05.007","volume":"15","author":"M Sinnreich","year":"2005","unstructured":"Sinnreich, M., Shaw, C. A., Pari, G., Nalbantoglu, J., Holland, P. C. & Karpati, G. Localization of coxsackie virus and adenovirus receptor (CAR) in normal and regenerating human muscle. Neuromuscular Disorders 15(8), 541\u2013548 (2005).","journal-title":"Neuromuscular Disorders"},{"key":"BFsrep33058_CR41","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.tips.2012.04.005","volume":"33","author":"N Arnberg","year":"2012","unstructured":"Arnberg, N. Adenovirus receptors: implications for targeting of viral vectors. Trends in Pharmacological Sciences 33(8), 442\u2013448 (2012).","journal-title":"Trends in Pharmacological Sciences"},{"key":"BFsrep33058_CR42","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1471-2121-5-42","volume":"5","author":"CA Shaw","year":"2004","unstructured":"Shaw, C. A., Holland, P. C., Sinnreich, M., Allen, C., Sollerbrant, K., Karpati, G. & Nalbantoglu, J. Isoform-specific expression of the Coxsackie and adenovirus receptor (CAR) in neuromuscular junction and cardiac intercalated discs. BMC Cell Biology, 5(1), 42 (2004).","journal-title":"BMC Cell Biology"},{"key":"BFsrep33058_CR43","first-page":"99","volume":"90","author":"NM Boulis","year":"1999","unstructured":"Boulis, N. M., Bhatia, V., Brindle, T. I., Holman, H. T., Krauss, D. J., Blaivas, M. & Hoff, J. T. Adenoviral nerve growth factor and beta-galactosidase transfer to spinal cord: a behavioral and histological analysis. Journal of Neurosurgery 90(1), 99\u2013108 (1999).","journal-title":"Journal of Neurosurgery"},{"key":"BFsrep33058_CR44","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.1046\/j.1460-9568.2000.00255.x","volume":"12","author":"AB Huber","year":"2000","unstructured":"Huber, A. B., Ehrengruber, M. U., Schwab, M. E. & Br\u00f6samle, C. Adenoviral gene transfer to the injured spinal cord of the adult rat. The European Journal of Neuroscience 12(9), 3437\u20133442 (2000).","journal-title":"The European Journal of Neuroscience"},{"key":"BFsrep33058_CR45","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/sj.gt.3301479","volume":"8","author":"S Yamashita","year":"2001","unstructured":"Yamashita, S., Mita, S., Arima, T., Maeda, Y., Kimura, E., Nishida, Y. et al. Bcl-2 expression by retrograde transport of adenoviral vectors with Cre-loxP recombination system in motor neurons of mutant SOD1 transgenic mice. Gene Therapy 8(13), 977\u2013986 (2001).","journal-title":"Gene Therapy"},{"key":"BFsrep33058_CR46","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1089\/104303402753812458","volume":"13","author":"G Acsadi","year":"2002","unstructured":"Acsadi, G., Anguelov, R. A., Yang, H., Toth, G., Thomas, R., Jani, A. et al. Increased Survival and Function of SOD1 Mice After Glial Cell-Derived Neurotrophic Factor Gene Therapy. Human Gene Therapy, 13(9), 1047\u20131059 (2002).","journal-title":"Human Gene Therapy"},{"key":"BFsrep33058_CR47","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0960-9822(01)00124-5","volume":"11","author":"R Kraut","year":"2001","unstructured":"Kraut, R., Menon, K. & Zinn, K. A gain-of-function screen for genes controlling motor axon guidance and synaptogenesis in Drosophila. Current Biology, 11(6), 417\u2013430 (2001).","journal-title":"Current Biology"},{"key":"BFsrep33058_CR48","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.cub.2015.03.028","volume":"25","author":"P Kratsios","year":"2015","unstructured":"Kratsios, P., Pinan-Lucarr\u00e9, B., Kerk, S. Y., Weinreb, A., Bessereau, J.-L. & Hobert, O. Transcriptional Coordination of Synaptogenesis and Neurotransmitter Signaling. Current Biology 25(10), 1282\u20131295 (2015).","journal-title":"Current Biology"},{"key":"BFsrep33058_CR49","first-page":"1106","volume":"12","author":"LT Alto","year":"2009","unstructured":"Alto, L. T., Havton, L. A., Conner, J. M., Hollis, E. R., II, Blesch, A. & Tuszynski, M. H. Chemotropic guidance facilitates axonal regeneration and synapse formation after spinal cord injury. Nature Publishing Group 12(9), 1106\u20131113 (2009).","journal-title":"Nature Publishing Group"},{"key":"BFsrep33058_CR50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cne.10593","volume":"459","author":"O Steward","year":"2003","unstructured":"Steward, O., Zheng, B. & Tessier-Lavigne, M. False resurrections: distinguishing regenerated from spared axons in the injured central nervous system. The Journal of Comparative Neurology, 459(1), 1\u20138 (2003).","journal-title":"The Journal of Comparative Neurology"},{"key":"BFsrep33058_CR51","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/gt.2014.121","volume":"22","author":"J Hordeaux","year":"2015","unstructured":"Hordeaux, J., Dubreil, L., Deniaud, J., Iacobelli, F., Moreau, S., Ledevin, M. et al. Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in adult and neonate rats. Gene Therapy 22(4), 316\u2013324 (2015).","journal-title":"Gene Therapy"},{"key":"BFsrep33058_CR52","doi-asserted-by":"crossref","first-page":"e65646","DOI":"10.1371\/journal.pone.0065646","volume":"8","author":"G Von Jonquieres","year":"2013","unstructured":"Von Jonquieres, G., Mersmann, N., Klugmann, C. B., Harasta, A. E., Lutz, B., Teahan, O. et al. Glial Promoter Selectivity following AAV-Delivery to the Immature Brain. PLoS ONE 8(6), e65646 (2013).","journal-title":"PLoS ONE"},{"key":"BFsrep33058_CR53","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1089\/10430349950018409","volume":"10","author":"J Nalbantoglu","year":"1999","unstructured":"Nalbantoglu, J., Pari, G., Karpati, G. & Holland, P. C. Expression of the primary coxsackie and adenovirus receptor is downregulated during skeletal muscle maturation and limits the efficacy of adenovirus-mediated gene delivery to muscle cells. Human Gene Therapy 10(6), 1009\u20131019 (1999).","journal-title":"Human Gene Therapy"},{"issue":"4","key":"BFsrep33058_CR54","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1093\/hmg\/3.4.579","volume":"3","author":"G Acsadi","year":"1994","unstructured":"Acsadi, G., Jani, A., Massie, B., Simoneau, M., Holland, P., Blaschuk, K. & Karpati, G. A differential efficiency of adenovirus-mediated in vivo gene transfer into skeletal muscle cells of different maturity. Human Molecular Genetics 3(4), 579\u2013584 (1994).","journal-title":"Human Molecular Genetics"},{"key":"BFsrep33058_CR55","doi-asserted-by":"crossref","first-page":"4276","DOI":"10.1128\/JVI.75.9.4276-4282.2001","volume":"75","author":"J Nalbantoglu","year":"2001","unstructured":"Nalbantoglu, J., Larochelle, N., Wolf, E., Karpati, G., Lochm\u00fcller, H. & Holland, P. C. Muscle-specific overexpression of the adenovirus primary receptor CAR overcomes low efficiency of gene transfer to mature skeletal muscle. Journal of Virology 75(9), 4276\u20134282 (2001).","journal-title":"Journal of Virology"},{"issue":"3","key":"BFsrep33058_CR56","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/jgm.1433","volume":"12","author":"N Larochelle","year":"2010","unstructured":"Larochelle, N., Teng, Q., Gilbert, R., Deol, J. R., Karpati, G., Holland, P. C. & Nalbantoglu, J. Modulation of coxsackie and adenovirus receptor expression for gene transfer to normal and dystrophic skeletal muscle. The Journal of Gene Medicine, 12(3), 266\u2013275 (2010).","journal-title":"The Journal of Gene Medicine"},{"key":"BFsrep33058_CR57","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nrn3821","volume":"15","author":"H Darabid","year":"2014","unstructured":"Darabid, H., Perez-Gonzalez, A. P. & Robitaille, R. Neuromuscular synaptogenesis: coordinating partners with multiple functions. Nature Reviews Neuroscience 15(11), 703\u2013718 (2014).","journal-title":"Nature Reviews Neuroscience"},{"key":"BFsrep33058_CR58","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1093\/hmg\/ddt659","volume":"23","author":"JN Sleigh","year":"2014","unstructured":"Sleigh, J. N., Grice, S. J., Burgess, R. W., Talbot, K. & Cader, M. Z. Neuromuscular junction maturation defects precede impaired lower motor neuron connectivity in Charcot\u2013Marie\u2013Tooth type 2D mice. Human Molecular Genetics 23(10), 2639\u20132650 (2014).","journal-title":"Human Molecular Genetics"},{"key":"BFsrep33058_CR59","unstructured":"Sleigh, J. N. & Schiavo, G. Older but not slower: aging does not alter axonal transport dynamics of signalling endosomes in vivo. Matters. 10.19185\/matters.201605000018 (2016)."},{"key":"BFsrep33058_CR60","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/mt.2011.243","volume":"20","author":"JM Zirger","year":"2012","unstructured":"Zirger, J. M., Puntel, M., Bergeron, J., Wibowo, M., Moridzadeh, R., Bondale, N. et al. Immune-mediated Loss of Transgene Expression From Virally Transduced Brain Cells Is Irreversible, Mediated by IFN\u03b3, Perforin, and TNF\u03b1, and due to the Elimination of Transduced Cells. Molecular Therapy: the Journal of the American Society of Gene Therapy 20(4), 808\u2013819 (2012).","journal-title":"Molecular Therapy: the Journal of the American Society of Gene Therapy"},{"key":"BFsrep33058_CR61","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2174\/156652307782151498","volume":"7","author":"PR Lowenstein","year":"2007","unstructured":"Lowenstein, P. R., Mandel, R. J., Xiong, W.-D., Kroeger, K. & Castro, M. G. Immune responses to adenovirus and adeno-associated vectors used for gene therapy of brain diseases: the role of immunological synapses in understanding the cell biology of neuroimmune interactions. Current Gene Therapy 7(5), 347\u2013360 (2007).","journal-title":"Current Gene Therapy"},{"key":"BFsrep33058_CR62","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1165\/ajrcmb.13.5.7576685","volume":"13","author":"BJ Petrof","year":"1995","unstructured":"Petrof, B. J., Acsadi, G., Jani, A., Massie, B., Bourdon, J., Matusiewicz, N. et al. Efficiency and functional consequences of adenovirus-mediated in vivo gene transfer to normal and dystrophic (mdx) mouse diaphragm. American Journal of Respiratory Cell and Molecular Biology, 13(5), 508\u2013517 (1995).","journal-title":"American Journal of Respiratory Cell and Molecular Biology"},{"key":"BFsrep33058_CR63","first-page":"212","volume":"96","author":"NM Boulis","year":"2002","unstructured":"Boulis, N. M., Turner, D. E., Imperiale, M. J. & Feldman, E. L. Neuronal survival following remote adenovirus gene delivery. Journal of Neurosurgery 96(2) (Suppl), 212\u2013219 (2002).","journal-title":"Journal of Neurosurgery"},{"key":"BFsrep33058_CR64","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0006-3495(02)75380-0","volume":"82","author":"Y Chen","year":"2002","unstructured":"Chen, Y., M\u00fcller, J. D., Ruan, Q. & Gratton, E. Molecular brightness characterization of EGFP in vivo by fluorescence fluctuation spectroscopy. Biophysical Journal, 82(1) (Pt 1), 133\u2013144 (2002).","journal-title":"Biophysical Journal"},{"key":"BFsrep33058_CR65","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1089\/neu.2010.1708","volume":"28","author":"R Morris","year":"2011","unstructured":"Morris, R., Tosolini, A. P., Goldstein, J. D. & Whishaw, I. Q. Impaired Arpeggio Movement in Skilled Reaching by Rubrospinal Tract Lesions in the Rat: A Behavioral\/Anatomical Fractionation. Journal of Neurotrauma 28(12), 2439\u20132451 (2011).","journal-title":"Journal of Neurotrauma"},{"key":"BFsrep33058_CR66","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1002\/ar.22549","volume":"295","author":"C Watson","year":"2007","unstructured":"Watson, C. & Harrison, M. The Location of the Major Ascending and Descending Spinal Cord Tracts in all Spinal Cord Segments in the Mouse: Actual and Extrapolated. Anatomical Record ( Hoboken, N.J., 2007), 295(10), 1692\u20131697 (2012).","journal-title":"Anatomical Record"},{"key":"BFsrep33058_CR67","doi-asserted-by":"crossref","first-page":"4657","DOI":"10.1523\/JNEUROSCI.23-11-04657.2003","volume":"23","author":"IA Kerman","year":"2003","unstructured":"Kerman, I. A., Enquist, L. W., Watson, S. J. & Yates, B. J. Brainstem substrates of sympatho-motor circuitry identified using trans-synaptic tracing with pseudorabies virus recombinants. Journal of Neuroscience 23(11), 4657\u20134666 (2003).","journal-title":"Journal of Neuroscience"},{"key":"BFsrep33058_CR68","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1126\/science.3961488","volume":"232","author":"EM Kurz","year":"1986","unstructured":"Kurz, E. M., Sengelaub, D. R. & Arnold, A. P. Androgens regulate the dendritic length of mammalian motoneurons in adulthood. Science 232(4748), 395\u2013398 (1986).","journal-title":"Science"},{"key":"BFsrep33058_CR69","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/(SICI)1097-4547(19970501)48:3<281::AID-JNR11>3.0.CO;2-4","volume":"48","author":"M Gim\u00e9nez y Ribotta","year":"1997","unstructured":"Gim\u00e9nez y Ribotta, M., Revah, F., Pradier, L., Loquet, I., Mallet, J. & Privat, A. Prevention of motoneuron death by adenovirus-mediated neurotrophic factors. Journal of Neuroscience Research 48(3), 281\u2013285 (1997).","journal-title":"Journal of Neuroscience Research"},{"key":"BFsrep33058_CR70","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1096\/fj.01-0321fje","volume":"15","author":"C Soudais","year":"2001","unstructured":"Soudais, C., Laplace-Builhe, C., Kissa, K. & Kremer, E. J. Preferential transduction of neurons by canine adenovirus vectors and their efficient retrograde transport in vivo. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 15(12), 2283\u20132285 (2001).","journal-title":"FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology"},{"key":"BFsrep33058_CR71","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1089\/10430340252769752","volume":"13","author":"S Millecamps","year":"2002","unstructured":"Millecamps, S., Mallet, J. & Barkats, M. Adenoviral retrograde gene transfer in motoneurons is greatly enhanced by prior intramuscular inoculation with botulinum toxin. Human Gene Therapy 13(2), pp. 225\u2013232 (2002).","journal-title":"Human Gene Therapy"},{"key":"BFsrep33058_CR72","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0304-3940(03)00817-6","volume":"350","author":"S Yamashita","year":"2003","unstructured":"Yamashita, S., Mita, S., Kato, S., Okado, H., Ohama, E. & Uchino, M. Bcl-2 expression using retrograde transport of adenoviral vectors inhibits cytochrome c-release and caspase-1 activation in motor neurons of mutant superoxide dismutase 1 (G93A) transgenic mice. Neuroscience Letters 350(1), 17\u201320 (2003).","journal-title":"Neuroscience Letters"},{"key":"BFsrep33058_CR73","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.molbrainres.2005.09.021","volume":"142","author":"L-K Tsai","year":"2005","unstructured":"Tsai, L.-K., Tsai, M.-S., Shyue, S.-K., Hwu, W.-L. & Li, H. Adenoviral interneuronal transportation after retrograde gene transfer in mice. Molecular Brain Research 142(2), 151\u2013155 (2005).","journal-title":"Molecular Brain Research"},{"key":"BFsrep33058_CR74","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.1016\/S0022-510X(98)00207-X","volume":"160","author":"G Haase","year":"1998","unstructured":"Haase, G., Pettmann, B., Vigne, E., Castelnau-Ptakhine, L. Schmalbruch, H. & Kahn, A. Adenovirus-mediated transfer of the neurotrophin-3 gene into skeletal muscle of pmn mice: Therapeutic effects and mechanisms of action. Journal of the Neurological Sciences 160, S97\u2013S105 (1998).","journal-title":"Journal of the Neurological Sciences"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep33058.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep33058","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep33058.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T09:58:49Z","timestamp":1718791129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep33058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,13]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,16]]}},"alternative-id":["BFsrep33058"],"URL":"https:\/\/doi.org\/10.1038\/srep33058","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,13]]},"assertion":[{"value":"23 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"33058"}}